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Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current Position Paper deals with surgical management, disease monitoring, immunization, bone health and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. Conclusion: This position paper provides a useful guide to clinicians in the surgical management, disease monitoring and various health issues in children with IBD in Asia Pacific region.

Background Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre‐treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration‐Hepatoblastoma Stratification (CHIC‐HS) system, with survival outcomes. Methods We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. Results The 5‐year overall survival (OS), event‐free survival (EFS), and transplant‐free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P, Survival rates were significantly improved among children with hepatoblastoma, especially those with advanced PRETEXT stages with positive annotation factors due to advances in surgical techniques and the introduction of effective chemotherapy. Prognostic factors had different clinical implications with evolved treatment modalities.

Pediatric patients with biliary atresia (BA) often present liver cirrhosis-associated portal hypertension and portal vein (PV) hypoplasia. For successful liver transplantation (LT), it is essential to maintain sufficient PV inflow through stenosis-free PV reconstruction with effective ligation of collateral veins. The aim of this study was to assess the clinical usability of intraoperative cine-portogram (IOCP) in young pediatric patients who underwent LT for BA.Medical records of pediatric patients younger than 10 years who underwent primary LT for BA from 2018 to 2020 were reviewed.A total of 31 patients had undergone Kasai portoenterostomy soon after birth. Their median ages at Kasai portoenterostomy and LT were 1 and 11 months, respectively. Types of LT were living-donor LT in 13, deceased-donor split LT in 15, and deceased-donor whole LT in three patients. PV interposition using an iliac vein homograft was performed in 28 patients receiving partial liver grafts. Side-to-side PV unification venoplasty was performed in three patients undergoing whole LT. All patients underwent ligation of collateral veins. IOCP was performed in 6 (19.4%) patients. Four showed no or faint residual venous collaterals. Collateral vein embolization and endovascular stenting were performed in one patient each. PV insufficiency-free survival rate was 100% at 1 year and 93.8% at 3 years. All patients are currently alive with a median follow-up period of 23 months.Intraoperative cine-portogram can be a useful method for identification and embolization of residual portosystemic collateral veins in young pediatric patients who undergo LT for biliary atresia.

This study aimed to investigate the incidence of PTLD in pediatric liver transplant recipients and the risk factors for the development of PTLD. We also determined clinically useful quantitative EBV PCR parameters for aiding in the diagnosis of EBV-associated PTLD in the pediatric liver transplant recipients at our institute. We reviewed children < 18 years old who had undergone liver transplantations and quantitative analysis of whole blood EBV load at our institute from January 2006 to March 2015. A total of 142 liver transplant recipients were included, and their median age was 1.5 years. Clinically significant high-level EBV DNAemia ≥ 10 000 copies/mL at least twice was observed in 53.5% and PTLD occurred in 9.9%. Among PTLD group, graft failure and mortality rate were as high as 21.4% and 14.3%, respectively. Deceased donor, presence of high-level EBV DNAemia, and primary CMV infection following transplant were associated with an increased risk for PTLD in the multivariate analysis. The peak titer at 10 875 copies/mL could be used as a cutoff value with a sensitivity of 92.9% and a specificity of 37.9%; the rate of increase in EBV load suggested a sensitivity of 64.3% and a specificity of 70.9% at the cutoff value of 44 000 copies/mL/week. In conclusion, the incidence of PTLD following liver transplant in children was as high as 10%. PTLD is associated with significant morbidity and mortality. Close monitoring of EBV DNAemia is crucial for the early diagnosis and proper treatment of PTLD in pediatric liver transplant recipients.

OBJECTIVES To assess the diagnostic performance of ultrasound (US) elastography in evaluating portal hypertension in children and compare the liver and spleen stiffness values between the portal hypertension and control groups. METHODS Studies in the MEDLINE and Embase databases were selected that investigated the diagnostic performance of US elastography in children with portal hypertension up to December 21, 2017. Pooled sensitivity and specificity data were assessed by hierarchical logistic regression modeling. RESULTS Eleven studies were included in the systematic review, and a meta-analysis could be conducted in 7 of these publications to evaluate the diagnostic performance of US elastography. The summary sensitivity and specificity of this method for liver stiffness were 90% (95% confidence interval [CI], 83%-94%) and 79% (95% CI, 73%-84%), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). A subgroup analysis of 5 transient elastographic studies revealed similar diagnostic performance (sensitivity, 90%; specificity, 78%). In 10 of the 11 studies that investigated liver stiffness and 2 of the 3 studies that also measured spleen stiffness, patients in the portal hypertension group had a significantly higher stiffness value than the control group (P

Background and aim CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS). Methods We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR. Results An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, Pcombined = 5.68 × 10-9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, Pcombined = 8.85 × 10-9 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine. Conclusions rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.

Background Genome-wide association studies have identified tumor necrosis factor superfamily member 15 (TNFSF15) as a Crohn's disease (CD)-related gene. The aim of this study was to evaluate the association between five TNFSF15 polymorphisms and CD in Korean children and analyze their genotypes in relation to phenotype. Methods Five single-nucleotide polymorphisms of TNFSF15 (rs3810936, rs6478108, rs6478109, rs7848647, rs7865494) were genotyped in 108 CD patients and in 599 healthy controls. Risk allele, genotype, and haplotype were analyzed in CD patients and controls, and genotype–phenotype relationships were studied. Results There were significant associations of rs3810936, rs6478108, rs6478109, rs7848647 with CD in Korean pediatric patients (P = 6.5×10-8, P = 1.3×10-8, P = 3.7×10-8, P = 2.9×10-8, respectively). The adjusted OR (aOR) for the homozygous risk allele genotype was significantly higher than that for the homozygous genotype for the opposite allele: rs3810936, aOR, 5.36 (95%CI: 2.61–10.98, P = 4.6×10-6); rs6478108, aOR, 6.62 (95%CI: 3.03–14.46, P = 2.2×10-6); rs6478109, aOR, 6.24 (95%CI: 2.85–13.66, P = 4.6×10-6); rs7848647, aOR, 6.32 (95%CI: 2.89–13.81, P = 3.8×10-6). The risk allele of rs3810936 was associated with later symptom onset, later diagnosis, and the presence of perianal lesion (P = 0.013, P = 0.016 and P = 0.029). Conclusion There was a significant association of TNFSF15 with pediatric CD in Korean patients.

Background Alagille syndrome (AGS) is a multisystem autosomal dominant disorder that affects the liver, heart, eyes, face, bone, and other organs. AGS is caused by mutations in one of two genes, JAG1 or NOTCH2. We evaluated clinical features, outcomes, and the presence of JAG1 and NOTCH2 mutations in Korean children with AGS. Methods Between January 1997 and December 2013, 19 children were diagnosed with AGS at Asan Medical Center, Seoul, Korea. Their clinical features, outcomes, and JAG1 and NOTCH2 mutation status were retrospectively analyzed. Results The prevalence of clinical features in the 19 patients was as follows: dysmorphic facial features, 100% (n = 19); liver symptoms, 89% (n = 17); cardiac symptoms, 95% (n = 18); ophthalmologic symptoms, 67% (n = 10); skeletal deformities, 47% (n = 9); and renal symptoms, 21% (n = 4). JAG1 mutations were identified in 14 patients. The 13 different JAG1 mutations, seven of which were novel, included four deletions, three insertions, two missense mutations, three nonsense mutations, and one indel mutation. No NOTCH2 mutations were found. Two patients who received liver transplantation due to liver failure were still alive. Two patients died of comorbidities related to AGS: one of cardiac failure and one of hepatic failure. Conclusion This study describes the clinical characteristics of 19 Korean AGS patients with seven novel JAG1 mutations. Neonatal cholestatic jaundice was the most common initial presenting symptom; thus the presence of neonatal cholestasis warrants screening for syndromic features of AGS. Complex heart anomalies and progressive liver dysfunction resulted in significant morbidity and mortality in AGS.

The origin and evolution of viruses remain mysterious. Here, we focus on the distribution of viral replicons in host organisms, their morphological features, and the evolution of highly conserved protein and nucleic acid structures. The apparent inability of RNA viral replicons to infect contemporary akaryotic species suggests an early origin of RNA viruses and their subsequent loss in akaryotes. A census of virion morphotypes reveals that advanced forms were unique to viruses infecting a specific supergroup, while simpler forms were observed in viruses infecting organisms in all forms of cellular life. Results hint toward an ancient origin of viruses from an ancestral virus harboring either filamentous or spherical virions. Finally, phylogenetic trees built from protein domain and tRNA structures in thousands of genomes suggest that viruses evolved via reductive evolution from ancient cells. The analysis presents a complete account of the evolutionary history of cells and viruses and identifies viruses as crucial agents influencing cellular evolution.

DNHB is common in countries with high prevalence of hepatitis B, and therefore, contracting hepatitis B after LT with HBcAb(+) grafts is a major concern. We studied DNHB in 247 children (aged

The advent of polymeric materials has significantly promoted the development and rapid growth of various technologies in biomedical applications, such as tissue engineering and controlled drug and gene delivery. Water-soluble polypeptides bearing functional side chains and adopting stable secondary structures are a new class of functional polymeric materials of potentially broad applications in medicine and biotechnology. In this article, we summarize our recent effort on the design and synthesis of the water-soluble �� -helical ionic polypeptides originally developed in our laboratory and highlight their applications in cell membrane penetration and nonviral gene/small interfering RNA (siRNA) delivery. © 2014 Wiley

The composition of lichen ecosystems except mycobiont and photobiont has not been evaluated intensively. In addition, recent studies to identify algal genotypes have raised questions about the specific relationship between mycobiont and photobiont. In the current study, we analyzed algal and fungal community structures in lichen species from King George Island, Antarctica, by pyrosequencing of eukaryotic large subunit (LSU) and algal internal transcribed spacer (ITS) domains of the nuclear rRNA gene. The sequencing results of LSU and ITS regions indicated that each lichen thallus contained diverse algal species. The major algal operational taxonomic unit (OTU) defined at a 99% similarity cutoff of LSU sequences accounted for 78.7-100% of the total algal community in each sample. In several cases, the major OTUs defined by LSU sequences were represented by two closely related OTUs defined by 98% sequence similarity of ITS domain. The results of LSU sequences indicated that lichen-associated fungi belonged to the Arthoniomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, and Sordariomycetes of the Ascomycota, and Tremellomycetes and Cystobasidiomycetes of the Basidiomycota. The composition of major photobiont species and lichen-associated fungal community were mostly related to the mycobiont species. The contribution of growth forms or substrates on composition of photobiont and lichen-associated fungi was not evident.

Despite the improved outcomes of LT, post-operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify the incidence of and risk factors for NCs in children who underwent LT. The medical records of pediatric patients who underwent LT at Asan Medical Center Children's Hospital between January 1994 and December 2010 were retrospectively analyzed. The onset and types of NC and pretransplant variables associated with NC were evaluated. We identified 190 children (85 boys [44.7%], 105 girls [55.3%]) of mean age 4.1 ± 4.7 yr, who underwent LT. Forty-six NCs occurred in 41 (21.6%) patients after LT, the most common being seizures (n = 13, 28.3%) and encephalopathy (n = 10, 21.7%). Of the 46 NCs, 24 (52.2%) occurred within three months after LT. Multivariate analysis showed that primary liver disease, preoperative neurological problems, preoperatively higher serum creatinine concentration, and graft failure were significant risk factors for NCs. The survival rate was significantly lower for patients with NCs than for those without (p < 0.001). NCs after pediatric LTs were common and associated with a higher mortality rate in our study. Close monitoring and appropriate risk management may improve the long-term outcomes of pediatric patients who undergo LT.

Background Children with acute liver failure (ALF) caused by hemophagocytic lymphohistiocytosis (HLH) may be at risk of undergoing unnecessary liver transplantation (LT). The aim of this study was to compare the characteristics of ALF caused by HLH with those of ALF of unknown etiology in children. Methods The clinical features and laboratory findings for eight children with ALF caused by HLH (ALF-HLH group) and 27 children with ALF of unknown etiology (ALF-UK group) were retrospectively compared by reviewing medical records. Results The ALF-HLH group had a higher incidence of pleural effusion, C-reactive protein elevation (especially >5 mg/dL), thrombocytopenia, anemia, fever, splenomegaly, and hypoalbuminemia (

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.

Background We evaluated the outcomes and prognostic factors, especially serum levels of alpha-fetoprotein (AFP) and their changes during the treatment of hepatoblastoma (HB). Procedure We retrospectively analyzed the medical records of 43 consecutive children with HB treated at a single institution between 1991 and 2010. Results Of 43 patients, 5 (12%) underwent primary tumor resection at diagnosis and 38 (88%) received preoperative chemotherapy. Of those 38 patients, 7 (16%) died of progressive disease during preoperative chemotherapy, and 31 (72%) underwent curative operations, including 5 who underwent liver transplantation, after a median 4 cycles of chemotherapy (range, 3–14 cycles). The 5-year overall survival and disease-free survival rates were 62.1 ± 8.3% and 65.6 ± 7.6%, respectively. AFP >263,000 ng/mL at diagnosis, a decline of

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous set of complications of organ transplantation associated with poor patient prognosis. We analyzed the clinicopathological features of PTLDs in 43 adult and pediatric recipients of solid organ or bone marrow transplantation at a large transplant service in the Republic of Korea between 1990 and 2009. Of 4545 solid organ and 747 bone marrow transplant recipients, 37 (0.81%) and 6 (0.8%), respectively, developed heterogeneous types of PTLDs. The cumulative incidences of PTLDs during this period were 1.79% (4/223) for heart transplant recipients, 0.78% (17/2192) for kidney transplant recipients, and 0.77% (16/2067) for liver transplant recipients. The patterns of disease onset, histology, and patient survival were associated with the types of organs transplanted. There is a trend for shorter overall survival (OS) in recipients with early-onset PTLDs and monomorphic PTLD histology, while kidney transplant recipients showed favorable OS. This study may be the first comprehensive analysis of the characteristics of PTLDs in Korean patients.

Background: Several putative virulence factors for Helicobacter pylori have been identified including cagA, vacA, and iceA. The aims of the present study were to study the distribution of cagA, vacA, and iceA genotypes in children with H. pylori gastritis and to examine the association of genotypes with severity of gastritis. Methods: H. pylori DNA was extracted from antral biopsy specimens from 33 children with H. pylori gastritis. Specific polymerase chain reaction assays were used for three genes: cagA, vacA, and iceA. The features of gastritis were graded in accordance with the updated Sydney System. Results: Of the 33 children, 31 (94%) were cagA positive. Twenty-four (72%) had s1c genotype and nine (27%) had s1a. The m1 genotype was seen in 27 (82%) and m2 was found in five (15%). The iceA1 genotype was detected in 25 (76%). Scores of neutrophil activity, chronic inflammation, and H. pylori density were independent of cagA, vacA and iceA status. Conclusion: The cagA-positive vacA s1c/m1 iceA1 genotype was predominant in Korean children with recurrent abdominal pain and H. pylori gastritis. The cagA, vacA and iceA genotype were not associated with the severity of gastritis.

Good yields were usually obtained in Pd(O)-catalyzed Suzuki aryl-aryl coupling reaction, even when both coupling partners had an ortho tertiary benzamide functional group. The direct ortho functionalization of oligomeric tertiary benzamides at Snieckus condition is dependent on the chain length. Tertiary benzamide 1 can be o,o-dilithiated only by metal-halogen exchange of the 2,6-dihalo-compound. Bis-tertiary benzamide 9 can be o,o'-dilithiated with excess(4.1 equivalents) s-butyllithium/TMEDA as the lithiating agent. Tris-tertiary benzamide 21 is hard to o,o"-difunctionalize due to steric interactions among the tertiary benzamide functional groups, and due to steric interactions between these functional groups and others (if present) on the termini of the terphenyl unit.