The Effect of Intrahepatic and Intrasplenic Administration of Mesenchymal Stem Cell to Liver Function and Degree of Liver Fibrosis in Common Bile Duct Ligation Model in Rabbit.

BACKGROUND: Mesenchymal stem cells (MSC) is a promising alternative method in liver cirrhosis management. Several administration routes of MSC have been studied, but few studies compared one to another. The purpose of this study is to compare the intrahepatic and intrasplenic route of MSC administration in terms of liver function and degree of liver fibrosis in the bile duct ligation model in rabbits. METHOD: Experimental study was conducted using rabbits (Oryctolagus cuniculus) model undergoing bile duct ligation (BDL). The subjects were randomized into 4 groups: sham surgery; bile duct ligation; bile duct ligation followed by intrahepatic route of MSC (BDL + IH MSC), and bile duct ligation followed by intrasplenic route of MSC (BDL + IS MSC). Umbilical cord mesenchymal stem cell (UC MSC) was administered on the fifth day after bile duct ligation, and the subjects were observed until the fourteenth day after bile duct ligation. The liver function was evaluated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total and direct bilirubin. The degree of fibrosis was evaluated with Laennec score, fibrosis area fraction, the number of viable and necrosis hepatocytes, and the number of hepatic progenitor cells. RESULT: The subjects were randomized into 4 groups: 2 in sham surgery group, and 7 in each of the following groups: BDL, BDL + IH MSC and BDL + IS MSC groups. The mortality rate in BDL group was 57.1 %, while mortality in BDL + IH MSC and BDL + IS MSC groups were 14.3 % and 28.6 % respectively. No significant difference was found regarding liver function in each group, such as AST, ALT, total, and direct bilirubin. Histopathology examination in almost every subject undergone bile duct ligation (regardless of MSC administration) showed degree of fibrosis of Laennec 4B. Fibrosis area fraction, the number of viable and necrotic hepatocytes, and progenitor cells were analyzed; no significant difference was found between BDL + IH MSC and BDL + IS MSC groups, but the groups administered with MSC showed a larger number of viable hepatocytes compared to BDL group. No difference was found between BDL + IH MSC and BDL + IS MSC groups in terms of liver function and histologic parameters. CONCLUSION: Administration of MSC increases the number of viable hepatocytes, but no difference was found in terms of liver function and degree of liver fibrosis between the intrahepatic route and intrasplenic route of administration. TYPE OF STUDY: Animal Research, Randomized Controlled Study. LEVEL OF EVIDENCE: Level I? (animal research is not indicated in the levels of evidence table in the journal website).

Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis.

Purpose: This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. Methods: A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale and statistically analyzed using RevMan 5.4 software. Results: A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07-0.66; I2=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91-2.56; I2=62%, p<0.0001). Conclusion: Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.

Pediatric sepsis profile in a tertiary-care hospital in Indonesia: a 4-year retrospective study.

AIM: This study aimed to explore the factors contributing to mortality and its management among pediatric sepsis patients at a single center in Indonesia. METHOD: We conducted a retrospective study of children admitted due to sepsis from January 2015 to December 2019 in an Indonesian tertiary hospital. RESULTS: The mortality rate of pediatric sepsis in our study was 76.1% among 176 records with outcome identified. Mortality was significantly associated with septic shock at triage, number of organ failure, intensive care unit admission, inotropic use, septic shock and severe sepsis during hospitalization. Timing of antibiotic use did not affect mortality. Death within the first 24 h occurred in 41.8% of subjects, mostly due to septic shock. CONCLUSION: This study illuminates the current state of pediatric sepsis management in our Indonesian hospital, revealing it as inadequate. Findings highlight the need for improved pre-hospital systems and sepsis recognition tools, and wider use of mechanical ventilators and advanced monitoring due to limited pediatric intensive care unit beds. Future research should focus on hospital-specific sepsis protocols to reduce pediatric sepsis mortality rates.

Prophylactic Antibiotics to Prevent Cholangitis in Children with Biliary Atresia After Kasai Portoenterostomy: A Meta-Analysis.

OBJECTIVES: A connection between the bowel and bile ducts after the Kasai hepatoportoenterostomy (HPE) procedure poses a risk of ascending cholangitis. There were only a few evidence-based consensuses on the benefits of prophylactic antibiotics. This study aims to assess the value of prophylactic antibiotics in reducing the risk of cholangitis following the Kasai HPE procedure. METHODS: Meta-analysis is performed using random-effects model from the search result of 5 online databases (PubMed, Google Scholar, EBSCO MEDLINE, ClinicalTrials.gov , and EuropePMC) from inception to October 27, 2021. The keywords used were "antibiotic," "antimicrobial," "Kasai," "portoenterostomy," "biliary atresia," and "bile duct atresia." Cochrane Risk of Bias tool and Newcastle-Ottawa Scale is used to assess the risk of bias. The outcomes are incidence of cholangitis and native liver survival. RESULTS: Six studies consisting of 4 cohorts and 2 cross-sectional studies were extracted. A total of 714 patients reported different cholangitis incidence after prophylactic antibiotics administration post-Kasai HPE. The incidence of cholangitis following Kasai HPE was not statistically significant among participants. There is conflicting evidence on the efficacy of antibiotics in prolonging native liver survival. CONCLUSIONS: The existing evidence does not support the administration of prophylactic antibiotics in preventing cholangitis after Kasai HPE among biliary atresia patients. Additionally, their roles in native liver survival are still inconclusive. The fact that there were heterogeneous method and antibiotic usage between existing studies must also be highlighted for better design in future studies.

Diagnostic challenges of hypoganglionosis based on immunohistochemical method.

Background: Hypoganglionosis resembles Hirschsprung's disease as in both diseases, patients may present with severe constipation or pseudo-obstruction. To date, diagnosis of hypoganglionosis is still difficult to be established due to lack of international consensus regarding diagnostic criteria. This study aims to evaluate the use of immunohistochemistry to provide objective support for our initial subjective impression of hypoganglionosis as well as to describe the morphological features of this study. Methods: This is a cross-sectional study. Three resected intestinal samples from patients with hypoganglionosis at Kyushu University Hospital, Fukuoka, Japan were included in this study. One healthy intestinal sample was used as control. All specimens were immunohistochemically stained with anti-S-100 protein, anti-α-smooth muscle actin (α-SMA), and anti-c-kit protein antibodies. Results: (I) S-100 immunostaining: hypoplasia of the myenteric ganglia and marked reduction of intramuscular nerve fibers were observed in several segments of the intestine. (II) α-SMA immunostaining: the pattern of the muscular layers was almost normal in all segments; however, some areas showed hypotrophy of the circular muscle (CM) layers and hypertrophy of the longitudinal muscle (LM) layers. (III) C-kit immunostaining: a decreased in the number of interstitial cells of Cajal (ICCs) was observed in almost all segments of the resected intestine, even around the myenteric plexus. Conclusions: Each segment of intestine in hypoganglionosis had different numbers of ICCs, sizes, and distributions of ganglions, as well as patterns of musculature, which may range from severely abnormal to nearly normal. Further investigations regarding the definition, etiology, diagnosis, and treatment of this disease should be performed to improve the prognosis of this disease.

Association Between Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire Score, Endoscopy and Biopsy in Children with Clinical Gastroesophageal Reflux Disease: A Prospective Study.

Purpose: Gastro esophageal reflux disease (GERD) is a burdensome disease affecting many children. A clinical examination is reported to be unreliable to diagnose GERD in children. This study aimed to investigate the relationship between the Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) and endoscopic and histopathological findings in children with symptoms suggesting GERD. Changes in the PGSQ score in children with esophagitis as response to one month therapy were recorded as secondary outcome. Methods: This is a prospective cohort study in the pediatric outpatient clinic in an Indonesian tertiary hospital. Children aged 2-17 years old with clinical symptoms suspected of GERD are included in the study. Blinded endoscopic and histopathological examination was performed in all patients before one month proton pump inhibitors (PPI) therapy. The PGSQ information was collected at inclusion and after one month PPI treatment. Results: Fifty-eight subjects were included. Esophagitis was found in 60.9% of subjects according to endoscopy and 58.6% according to histology. There was no significant relationship between the PGSQ score and endoscopic (p=0.781) nor biopsy (p=0.740) examinations. The PGSQ showed a low diagnostic value compared to endoscopy and biopsy (area under the curve [AUC] 0.477, p=0.477, 95% confidence interval [CI] 0.326-0.629 and AUC 0.474, p=0.740 (95% CI 0.321-0.627 respectively). The PGSQ improved significantly post one month of PPI treatment. Conclusion: The PGSQ cannot be used to diagnose esophagitis in children with clinical symptoms suggesting GERD. However, the PGSQ can be used to monitor the treatment response in children with esophagitis.

The Role of Pretransplant Infections in Pediatric Receiving LDLT in Indonesia: A 7-y Retrospective Study.

Liver transplantation is the definitive treatment for pediatric end-stage liver disease. Infections posttransplantation might significantly affect the outcome of the surgery. This study aimed to identify the role of pretransplant infection among children who underwent living donor liver transplantation (LDLT) in Indonesia. Methods: This is an observational, retrospective cohort study. A total of 56 children were recruited between April 2015 and May 2022. Patients were categorized into 2 according to the presence of pretransplantation infections requiring hospitalization before the surgery. Diagnosis of posttransplantation infection was observed for up to 1 y based on the clinical features and laboratory parameters. Results: The most common indication for LDLT was biliary atresia (82.1%). Fifteen of 56 patients (26.7%) had a pretransplant infection, whereas 73.2% of patients were diagnosed with a posttransplant infection. There was no significant association between pretransplant and posttransplant infection in all 3-time points (≤1 mo, 2-6 mo, and 6-12 mo). The most common organ involvement posttransplantation was respiratory infections (50%). The pretransplant infection did not significantly affect posttransplant bacteremia, length of stay, duration of mechanical ventilation, initiation of enteral feeding, hospitalization cost, and graft rejection. Conclusions: Our data showed that pretransplant infections did not significantly affect clinical outcomes in post-LDLT procedures. A prompt and sufficient diagnosis and treatment before and after the LDLT procedure is the best way to obtain an optimal outcome.

Educational videos to address vaccine hesitancy in childhood immunization.

BACKGROUND: As one of the essential programs that have been developed for decades, childhood immunizations are mandatory to protect children from vaccine-preventable diseases. Despite its availability and accessibility, immunization coverage has not reached the intended goals. Vaccine hesitancy and COVID-19 pandemic may threaten immunization coverage in children. This study aimed to evaluate the tailored educational videos to reduce vaccine hesitancy and analyze the changes in childhood routine immunization status. METHODS: This was an interventional quasi-experimental study in three subdistricts of North Jakarta, Indonesia. Participants were allocated into educational videos exposures (intervention group, n = 116) or to the digital version of the maternal and child health handbook (control group, n = 104). We administered a pre- and post-intervention vaccine hesitancy survey using the Parent Attitudes about Childhood Vaccines (PACV) questionnaire with cut-off scores of 50. RESULTS: A total of 220 parents were recruited in this study from June 18, 2021, to December 10, 2021. The pre-intervention PACV survey showed that 19 (8.6%) parents were vaccine-hesitant from both groups: 12 (10.3%) and 7 (6.7%) of parents among intervention and control groups. After the interventions, there were 8 (6.9%) and 8 (7.7%) vaccine-hesitant parents in the intervention and control groups, respectively. We found a significant difference in the post-intervention PACV median score between the intervention and control groups (17 vs 23; p = 0.035). Around 25% of parents have not completed their children's immunization status: 22.4% and 28.8% in the intervention and control groups, respectively. There was a significant difference between the proportion of PACV hesitancy on the immunization status within intervention and control groups (p = 0.001). CONCLUSION: There was a reduction in vaccine hesitancy after interventions. Educational videos intervention distributed through WhatsApp group was associated with lower vaccine hesitancy and can be used as health education tools among Indonesian parents in the community.

Clinical Features of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in Indonesia.

BACKGROUND: While the number of cases of multisystem inflammatory syndrome in children (MIS-C) is increasing, reported cases in Asian countries are still low, particularly in Indonesia. This study aimed to describe the characteristics of patients with MIS-C in a tertiary referral hospital in Indonesia. METHODS: This is a cross-sectional study with collected data of patients with MIS-C admitted to Dr. Cipto Mangunkusumo from March 2020 to April 2021. RESULTS: The first case of MIS-C was detected 5 months after the first reported coronavirus disease 2019 case in Indonesia. Thirteen patients out of 158 positive admitted patients for COVID-19 were diagnosed with MIS-C during the study period. Of these 13 patients, 2 patients (15%) had a fatal outcome. Subjects were predominantly male, and the median age was 7.58 years (IQR 12.3) years. Most patients required mechanical ventilation (7 out of 13 patients) and intubation (8 out of 13 patients). Patients who needed intubation usually needed mechanical ventilation. All inflammatory markers, white blood cells, neutrophil counts, and all coagulation factor parameters (except for normal prothrombin time and activated partial prothrombin time) were elevated. The median time to MIS-C diagnosis was 2 days in the survivor group (n = 11) compared to 8.5 days in the non-survivor group (n = 2). Compared to the non-survivor group, those who survived spent more days in the hospital, received vasopressors earlier, and did not require mechanical ventilation as early as the non-survivors. CONCLUSIONS: Our work highlights the differences in MIS-C clinical course, treatment, and clinical outcomes between the two groups.

Parents' Perspectives Toward School Reopening During COVID-19 Pandemic in Indonesia-A National Survey.

Background: All sectors are affected due to COVID-19 pandemic occurring worldwide, including the education industry. School closure had been taking place for more than a year in Indonesia. Despite the controversies, Indonesian government had decided to begin school reopening. Objectives: This study aims to assess parental readiness for school reopening, and factors affecting parental attitude toward school reopening. Methods: A cross-sectional study using online questionnaire distributed via official Indonesian Pediatric Society (IPS) official social media account collected between March and April 2021. The questionnaire contained the general characteristics of study participants, parents' knowledge, and perspectives on COVID-19, and health protocols for school reopening. Results: A total of 17,562 responses were collected, of which 55.7% parents were ready to send their children to school should school reopens. Factors significantly contribute to parental decision to keep their child at home were: presence of vulnerable population at home [OR = 1.18 (1.10-1.27), p < 0.001], children with comorbidities [OR = 2.56 (2.29-2.87), p < 0.001], perception of COVID-19 as a dangerous disease [OR = 28.87 (14.29-58.33), p < 0.001], experience with COVID-19 positive cases in the community [OR = 1.75 (1.61-1.90), p < 0.001], COVID-19 related death in the community [OR = 2.05 (1.90-2.21), P < 0.001], approval for adult COVID-19 vaccination [OR = 1.69 (1.53-1.87), p < 0.001], and ownership of private transportation [OR = 1.46 (1.30-1.66), p <0.001]. Conclusion: We identified several factors affecting parental perception on school reopening during COVID-19 pandemic that should be addressed. This study can be used for policy-maker to make further recommendations and health educations prior to school reopening in Indonesia.

Correlation between syndecan-1 level and PELOD-2 score and mortality in pediatric sepsis. / Correlação entre níveis de sindecano 1, escore PELOD-2 e mortalidade em sepse pediátrica.

OBJECTIVE: To analyze the correlation between glycocalyx disruption measured via the serum syndecan-1 level and organ dysfunctions assessed by the PELOD-2 score and to evaluate its association with mortality in pediatric sepsis. METHODS: We performed a prospective observational study in a tertiary public hospital. Sixty-eight pediatric patients diagnosed with sepsis according to International Pediatric Sepsis Consensus Conference criteria were consecutively recruited. We performed measurements of day 1 and day 5 serum syndecan-1 levels and PELOD-2 score components. Patients were followed up to 28 days following sepsis diagnosis. RESULTS: Overall, the syndecan-1 level was increased in all subjects, with a significantly higher level among septic shock patients (p = 0.01). The day 1 syndecan-1 level was positively correlated with the day 1 PELOD-2 score with a correlation coefficient of 0.35 (p = 0.003). Changes in syndecan-1 were positively correlated with changes in the PELOD-2 score, with a correlation coefficient of 0.499 (p < 0.001) during the first five days. Using the cutoff point of day 1 syndecan-1 ≥ 430ng/mL, organ dysfunction (PELOD-2 score of ≥ 8) could be predicted with an AUC of 74.3%, sensitivity of 78.6%, and specificity of 68.5% (p = 0.001). CONCLUSION: The day 1 syndecan-1 level was correlated with the day 1 PELOD-2 score but not 28-day mortality. Organ dysfunction (PELOD-2 ≥ 8) could be predicted by the syndecan-1 level in the first 24 hours of sepsis, suggesting its significant pathophysiological involvement in sepsis-associated organ dysfunction.

OBJETIVO: Analisar a correlação entre a lesão do glicocálix medida pelo nível sérico de sindecano 1 e as disfunções de órgãos avaliadas com o escore PELOD-2, assim como avaliar sua associação com a mortalidade em sepse pediátrica. MÉTODOS: Realizou-se um estudo prospectivo observacional em um hospital terciário público. Sessenta e oito pacientes pediátricos, com diagnóstico de sepse segundo os critérios da International Pediatric Sepsis Consensus Conference, foram consecutivamente recrutados. Nos dias 1 e 5, realizaram-se dosagens dos níveis séricos de sindecano 1 e avaliação dos componentes do escore PELOD-2. Os pacientes foram seguidos por até 28 dias após o diagnóstico de sepse. RESULTADOS: Em geral, o nível de sindecano 1 estava aumentado em todos os participantes, com nível significantemente mais elevado nos pacientes em choque (p = 0,01). O nível de sindecano 1 no dia 1 teve correlação positiva com o escore PELOD-2 no dia 1 e coeficiente de correlação de 0,35 (p = 0,003). Nos primeiros 5 dias após o diagnóstico de sepse, as alterações nos níveis de sindecano 1 tiveram correlação positiva com modificações no escore PELOD-2, com coeficiente de correlação de 0,499 (p < 0,001). Com utilização de um ponto de corte dos níveis de sindecano 1 no dia 1 ≥ 430ng/mL, a disfunção de órgãos (escore PELOD-2 ≥ 8) pôde ser predita com área sob a curva de 74,3%, sensibilidade de 78,6% e especificidade de 68,5% (p = 0,001). CONCLUSÃO: O nível de sindecano 1 no dia 1 teve correlação com o escore PELOD-2 no dia 1, porém não se associou com a mortalidade aos 28 dias. A disfunção de órgãos (PELOD-2 ≥ 8) pôde ser predita pelo nível de sindecano 1 nas primeiras 24 horas de sepse, sugerindo seu significante envolvimento na fisiopatologia da disfunção de órgãos associada à sepse.

Serum NT-Pro-BNP versus Noninvasive Bedside Inotropic Index in Paediatric Shock: A Contest of Myocardial Performance in Response to Fluid Loading.

BACKGROUND: Mild elevation of serum amino-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is associated with myocardial dysfunction. A significantly lower Smith-Madigan inotropic index (SMII) has been shown to accurately represent cardiac contractility among heart failure subjects. We aim to monitor the effect of fluid resuscitation on cardiac function among paediatric patients by measuring serum NT-pro-BNP and SMII. METHODS: This is an observational study on 70 paediatric shock patients. NT-pro-BNP and noninvasive bedside haemodynamic monitoring were done by using an ultrasonic cardiac output monitor (USCOM, USCOM, Sydney, Australia). The presence of cardiac diseases was excluded. SMII was obtained from the USCOM. An increase in the stroke volume index (SVI) of ≥15% indicates fluid responders. Measurements were taken before and after fluid loading. RESULTS: Preloading NT-pro-BNP and SMII category were significantly different between the fluid responsiveness group, p=0.001 and p=0.004, respectively. Higher median NT-pro-BNP (preloading NT-pro-BNP of 1175.00 (254.50-9965.00) ng/mL vs. 196.00 (65.00-509.00) ng/mL, p=0.002) was associated with fluid nonresponders (subjects >12 months old). Preloading NT-pro-BNP <242.5 ng/mL was associated with fluid responders (AUC: 0.768 (0.615-0.921), p=0.003), 82.1% sensitivity, and 68.7% specificity for subjects >12 years old. Delta NT-pro-BNP in fluid responders (15.00 (-16.00-950.00) ng/mL) did not differ from fluid nonresponders (505.00 (-797.00-1600.00) ng/mL), p=0.456. Postloading SMII >1.25 W·m-2 was associated with fluid responders (AUC: 0.683 (0.553-0.813), p = 0.011), 61.9% sensitivity, and 66.7% specificity, but not preloading SMII. Fluid responders had a higher mean postloading SMII compared to nonresponders (1.36 ± 0.38 vs. 1.10 ± 0.34, p=0.006). CONCLUSION: Higher NT-pro-BNP and lower SMII in the absence of cardiac diseases were associated with poor response to fluid loading. The SMII is affected by low preload conditions.

Correlação entre níveis de sindecano 1, escore PELOD-2 e mortalidade em sepse pediátrica / Correlation between syndecan-1 level and PELOD-2 score and mortality in pediatric sepsis

RESUMO Objetivo: Analisar a correlação entre a lesão do glicocálix medida pelo nível sérico de sindecano 1 e as disfunções de órgãos avaliadas com o escore PELOD-2, assim como avaliar sua associação com a mortalidade em sepse pediátrica. Métodos: Realizou-se um estudo prospectivo observacional em um hospital terciário público. Sessenta e oito pacientes pediátricos, com diagnóstico de sepse segundo os critérios da International Pediatric Sepsis Consensus Conference, foram consecutivamente recrutados. Nos dias 1 e 5, realizaram-se dosagens dos níveis séricos de sindecano 1 e avaliação dos componentes do escore PELOD-2. Os pacientes foram seguidos por até 28 dias após o diagnóstico de sepse. Resultados: Em geral, o nível de sindecano 1 estava aumentado em todos os participantes, com nível significantemente mais elevado nos pacientes em choque (p = 0,01). O nível de sindecano 1 no dia 1 teve correlação positiva com o escore PELOD-2 no dia 1 e coeficiente de correlação de 0,35 (p = 0,003). Nos primeiros 5 dias após o diagnóstico de sepse, as alterações nos níveis de sindecano 1 tiveram correlação positiva com modificações no escore PELOD-2, com coeficiente de correlação de 0,499 (p < 0,001). Com utilização de um ponto de corte dos níveis de sindecano 1 no dia 1 ≥ 430ng/mL, a disfunção de órgãos (escore PELOD-2 ≥ 8) pôde ser predita com área sob a curva de 74,3%, sensibilidade de 78,6% e especificidade de 68,5% (p = 0,001). Conclusão: O nível de sindecano 1 no dia 1 teve correlação com o escore PELOD-2 no dia 1, porém não se associou com a mortalidade aos 28 dias. A disfunção de órgãos (PELOD-2 ≥ 8) pôde ser predita pelo nível de sindecano 1 nas primeiras 24 horas de sepse, sugerindo seu significante envolvimento na fisiopatologia da disfunção de órgãos associada à sepse.

ABSTRACT Objective: To analyze the correlation between glycocalyx disruption measured via the serum syndecan-1 level and organ dysfunctions assessed by the PELOD-2 score and to evaluate its association with mortality in pediatric sepsis. Methods: We performed a prospective observational study in a tertiary public hospital. Sixty-eight pediatric patients diagnosed with sepsis according to International Pediatric Sepsis Consensus Conference criteria were consecutively recruited. We performed measurements of day 1 and day 5 serum syndecan-1 levels and PELOD-2 score components. Patients were followed up to 28 days following sepsis diagnosis. Results: Overall, the syndecan-1 level was increased in all subjects, with a significantly higher level among septic shock patients (p = 0.01). The day 1 syndecan-1 level was positively correlated with the day 1 PELOD-2 score with a correlation coefficient of 0.35 (p = 0.003). Changes in syndecan-1 were positively correlated with changes in the PELOD-2 score, with a correlation coefficient of 0.499 (p < 0.001) during the first five days. Using the cutoff point of day 1 syndecan-1 ≥ 430ng/mL, organ dysfunction (PELOD-2 score of ≥ 8) could be predicted with an AUC of 74.3%, sensitivity of 78.6%, and specificity of 68.5% (p = 0.001). Conclusion: The day 1 syndecan-1 level was correlated with the day 1 PELOD-2 score but not 28-day mortality. Organ dysfunction (PELOD-2 ≥ 8) could be predicted by the syndecan-1 level in the first 24 hours of sepsis, suggesting its significant pathophysiological involvement in sepsis-associated organ dysfunction.

Echovirus-7 Infection in Children with Unusual Severe Manifestation: A Case Report.

We report a rare laboratory-confirmed, clinical case of Echovirus-7 infection in an immuno-competent child with central nervous system and systemic manifestation. Echovirus infection is usually mild, however in this case we identified echovirus-7 infection with 91% homology with the Echovirus-7 strain previously isolated in neighbouring country with severe manifestation.

Alopecia in Children Following Living Related Liver Transplantation.

INTRODUCTION: Alopecia is a common complication in patients following kidney transplantation; however, reports regarding liver transplantation patients are still few. METHODS: This study followed 111 children who underwent living related liver transplantation. Alopecia patients and its possible risk factors were analyzed. RESULTS: Alopecia occurred in 3 patients (2.7%). Underlying diseases were biliary atresia and Alagille syndrome. Clinically significant alopecia (universal alopecia) occurred in 1 patient with Alagille syndrome. All patients received tacrolimus as their immunosuppression drug. None of the patients who received cyclosporine experienced alopecia. The onset of alopecia ranged from 7 to 28 months after transplantation. Alopecia was treated with a topical corticosteroid and topical tacrolimus, but 1 patient with clinically severe alopecia required conversion from tacrolimus to cyclosporine A. CONCLUSIONS: Alopecia is 1 complication seen in children receiving tacrolimus therapy following living donor liver transplant. Prompt management of this cosmetic complication should be done to ensure patients' compliance to medication regimen.

Peroxisome Proliferator-Activated Receptor Gamma Agonist Attenuates Liver Fibrosis by Several Fibrogenic Pathways in an Animal Model of Cholestatic Fibrosis.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. METHODS: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. RESULTS: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-ß1) was also downregulated in the BDL+TZD group (p=0.0087). CONCLUSION: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-ß1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

Modified Puestow Procedure for Chronic Pancreatitis in a Child Due to Annular Pancreas and Duodenal Duplication: A Case Report.

An 18-year-old woman with annular pancreas and duodenal duplication presented with recurrent acute pancreatitis and underwent a resection of duodenal duplication. However, the patient experienced recurrent abdominal pain after resection. Abdominal computed tomography and magnetic resonance imaging showed a dilatation of the peripheral pancreatic duct and stenosis and malformation of both the Wirsung's and Santorini's duct due to multiple stones. The modified puestow procedure was performed. The main pancreatic ducts in the body and tail were opened, and the intrapancreatic common bile duct was preserved. A Roux-en-Y pancreatico-jejunostomy was performed for reconstructing the pancreaticobiliary system after removing the ductal protein plug. The patient experienced no abdominal pain, no significant elevation of the serum amylase and lipase levels, and no stone formation during the 2 years of follow-up. This procedure is considered to be beneficial for pediatric patients with chronic pancreatitis due to annular pancreas and duodenal duplication.

Functional abdominal pain disorders in adolescents in Indonesia and their association with family related stress.

BACKGROUND: Functional abdominal pain disorders (FAPD) have been widely reported as a major group of gastrointestinal disorders across the world. This study describes the prevalence, related factors, symptomatology and its relationship to emotional stress in Indonesian adolescents. METHODS: This is a cross-sectional study. Adolescents aged 10 to 17 years from nine randomly selected state schools from five districts of Jakarta, Indonesia, were invited to participate. A translated and validated Rome-III self-administered-questionnaire was used to collect data on gastrointestinal symptoms. Data on sociodemographic characteristics, intestinal as well as extra-intestinal symptoms, and exposure to stressful life events were also collected using a separate validated questionnaire. RESULTS: A total of 1813 questionnaires were included in the analysis [males 739 (40.8%) mean age of 13.54 years + 0.89]. Of them, 209 children (11.5%) fulfilled Rome III criteria of FAPD. Functional abdominal pain (FAP) was reported as the most prevalent subtype (5.8%), followed by functional dyspepsia (3.3%), irritable bowel syndrome (2%) and abdominal migraine (0.4%). The prevalence was higher in girls (p < 0.05) and those exposed to family-related stressful life events (p < 0.05). They include divorce or separation of parents (adjusted OR 2.55, 95% CI 1.75-3.7, p = < 0.001), death of a close family member (adjusted OR 2.24, 95% CI 1.39-3.59, P = 0.001), and father's alcoholism (adjusted OR 1.94, 95% CI 1.22-3.1, P = 0.005). CONCLUSIONS: FAPD are common paediatric entities among Indonesian adolescents with a prevalence of 11.5%. FAPD were noted to be higher in girls and adolescents exposed to family-related stressful life events.

Epidemiology of Paediatric constipation in Indonesia and its association with exposure to stressful life events.

BACKGROUND: We aimed to study the epidemiology and risk factors, including exposure to emotional stress, for constipation in Indonesian children and adolescents of 10-17 year age group. METHODS: A cross-sectional survey using a validated, self-administered questionnaire was conducted in randomly selected children and adolescents in nine state junior high schools from five districts of Jakarta. All of them were from urban areas. Constipation was defined as a diagnosis by using the Rome III criteria. RESULTS: Of 1796 children included in the analysis, 328 (18.3%; 95% CI 016-0.2) had constipation. Females and those residing in North Jakarta showed risks associated with constipation in school-age children and adolescents. Symptoms independently associated with constipation were abdominal pain (64% vs 43.3% of control) and straining (22.9% vs 6.3%). The prevalence of constipation was significantly higher in those with stressful life events such as father's alcoholism (adjusted OR 1.91, 95% CI 1.27-2.89, P = 0.002), severe illness of a close family member (adjusted OR 1.77, 95% CI 1.12-2.80, P = 0.014), hospitalization of the child for another illness (adjusted OR 1.68, 95% CI 1.22-2.31, P < 0.001), being bullied at school (adjusted OR 1.67, 95% CI 1.01-2.76, P = 0.047) and loss of a parent's job (adjusted OR 1.39, 95% CI 1.03-1.88, P = 0.034). CONCLUSIONS: Constipation in children and adolescent is a significant health problem, affecting almost 20% of Indonesian school-age children and adolescents. Common school and home related stressful life events appear to have predisposed these children to develop constipation.

In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice.

INTRODUCTION: Liver transplantation is a gold standard treatment for intractable liver diseases. Because of the shortage of donor organs, alternative therapies have been required. Due to their potential to differentiate into a variety of mature cells, stem cells are considered feasible cell sources for liver regeneration. Stem cells from human exfoliated deciduous teeth (SHED) exhibit hepatogenic capability in vitro. In this study, we investigated their in vivo capabilities of homing and hepatocyte differentiation and therapeutic efficacy for liver disorders in carbon tetrachloride (CCl4)-induced liver fibrosis model mice. METHODS: We transplanted SHED into CCl4-induced liver fibrosis model mice through the spleen, and analyzed the in vivo homing and therapeutic effects by optical, biochemical, histological, immunological and molecular biological assays. We then sorted human leukocyte antigen-ABC (HLA-ABC)-positive cells from primary CCl4-damaged recipient livers, and analyzed their fusogenicity and hepatic characteristics by flow cytometric, genomic DNA, hepatocyte-specific gene assays. Furthermore, we examined the treatment effects of HLA-positive cells to a hepatic dysfunction by a secondary transplantation into CCl4-treated mice. RESULTS: Transplanted SHED homed to recipient livers, and expressed HLA-ABC, human hepatocyte specific antigen hepatocyte paraffin 1 and human albumin. SHED transplantation markedly recovered liver dysfunction and led to anti-fibrotic and anti-inflammatory effects in the recipient livers. SHED-derived HLA-ABC-positive cells that were sorted from the primary recipient liver tissues with CCl4 damage did not fuse with the host mouse liver cells. Sorted HLA-positive cells not only expressed human hepatocyte-specific genes including albumin, cytochrome P450 1A1, fumarylacetoacetase, tyrosine aminotransferase, uridine 5'-diphospho-glucuronosyltransferase, transferrin and transthyretin, but also secreted human albumin, urea and blood urea nitrogen. Furthermore, SHED-derived HLA-ABC-positive cells were secondary transplanted into CCl4-treated mice. The donor cells homed into secondary recipient livers, and expressed hepatocyte paraffin 1 and human albumin, as well as HLA-ABC. The secondary transplantation recovered a liver dysfunction in secondary recipients. CONCLUSIONS: This study indicates that transplanted SHED improve hepatic dysfunction and directly transform into hepatocytes without cell fusion in CCl4-treated mice, suggesting that SHED may provide a feasible cell source for liver regeneration.