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A scoping review of the literature pertaining to the pathophysiology and immunological mechanisms of acute pancreatitis in humans.

The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre.A retrospective review was performed of patients aged 0-18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥20 seconds or international normalised ratio (INR) ≥2.0 regardless of hepatic encephalopathy (HE) or PT ≥15 seconds or INR ≥1.5 in the presence of HE.34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants12 months (38.9%), whereas an indeterminate cause was the most common in children12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%.The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.

Sulphite oxidase deficiency is an extremely rare inborn error of metabolism of sulphur containing amino acids. There are no reports of liver involvement in this condition. The authors describe a 9-y-old boy with known sulphite oxidase deficiency who presented with worsening cholestatic hepatitis which may be possibly related to underlying metabolic disorder. Although there is no current evidence that treating liver disease and ensuring normal hepatic function in sulphite oxidase deficiency would likely benefit patients, this could potentially contribute to optimising growth and development as well as improving the overall prognosis.

Autism Spectrum disorder (ASD) is well known to be associated with significantly high rates of gastrointestinal problems, constipation being common among them, imposing a significant burden on child and the family. On account of multiple underlying factors, both diagnosis and subsequent management of constipation in children with ASD are much more challenging as compared to managing constipation in 'neurotypical' children. Associated higher rate of presentation to the hospital emergency and subsequent hospital admission rates add to the burden. Hence, there is a need for recognizing constipation as a problem in children with ASD. This review summarizes optimization of its management by adopting a multidisciplinary holistic approach to achieve good outcomes and enhance the quality of life for the child and the family.

Patients with GSD type 1 (von Gierke disease) are initially managed medically to maintain normoglycemia. However, if they do not achieve good metabolic control, LT is then considered. We describe the long-term outcome of 6 children with GSD type 1 who underwent LT. Retrospective chart review of the data of 6 children with GSD type 1 who underwent LT at National University Hospital, Singapore, from May 1998 to October 2018, was performed. The median (IQR) age at diagnosis of the GSD was 1 year (0.92-5.50) and at transplant was 13.88 years (11.46-16.38). All of the patients had elevated liver enzymes, hypercholesterolemia, hypertriglyceridemia, and hyperlactatemia prior to transplant. All of the patients are alive at the time of analysis and follow-up. None of them required a re-transplant. For the three patients who had hypoglycemia pretransplant, there was no recurrence post-transplant. All of the patients had normalization of liver enzymes by 1 year post-transplant. Long-term outcome of patients with GSD who underwent LT has been positive with improvement in metabolic control for most patients. We report the unusual finding of two siblings with persistent hyperuricemia post-transplant requiring allopurinol.

Sulphite oxidase deficiency is an extremely rare inborn error of metabolism of sulphur containing amino acids. There are no reports of liver involvement in this condition. The authors describe a 9-y-old boy with known sulphite oxidase deficiency who presented with worsening cholestatic hepatitis which may be possibly related to underlying metabolic disorder. Although there is no current evidence that treating liver disease and ensuring normal hepatic function in sulphite oxidase deficiency would likely benefit patients, this could potentially contribute to optimising growth and development as well as improving the overall prognosis.

Background: The diagnosis of tuberculosis (TB) by microbiological tests is a major challenge particularly in children. The use of Xpert analysis, a rapid genetic testing modality is not widely reported in our locality. The aim of the study to evaluate the diagnostic accuracy of Gene xpert analysis in diagnosis of pediatric Pulmonary TB.Methods: A prospective hospital-based study was conducted among 140 participants with symptomatology pertaining to pulmonary TB as per Revised national tuberculosis control program (RNTCP, India) criteria. The Xpert testing (GXT) was performed as per standards and was compared with erythrocyte sedimentation rate (ESR), tuberculin test (TT) and chest X-rays (CXR). The obtained results were reported in terms of Sensitivity %, Specificity %, Positive Predictive Value % (PPV) and Negative Predictive Value % (NPV) for comparisons. The receiver operating curve (ROC) analysis was employed to evaluate the accuracy of diagnosis.Results: The GXT was positive (10.71 %) in suspected TB patients. TT has significantly (10 %) with a73.33% sensitivity, 93.60% specificity and a PPV of 57.89 % when compared with xpert. The ESR showed a sensitivity of 53.33% and a specificity of 56%. The CXR showed sensitivity of 93.33%. The ROC analysis showed that TT had a higher confidence interval (0.699-0.970) t5`han other methods. The Rifampicin resistance was found 7.5% (n=2) of 15 GXT positive cases.Conclusions: The xpert based diagnosis of gastric lavage samples after a tuberculin test (TT) had high sensitivity and specificity, followed by chest X ray while the ESR had lower clinical accuracy. The ‘gene xpert analysis’ is highly useful rapid tool for diagnosis of children with TB.

OBJECTIVES Routine oesophago-gastro-duodenoscopy (OGD) pre-liver transplantation (LT) for evaluation and management of gastrointestinal (GI) pathology, in particular GI varices secondary to portal hypertension, is common practice in adult LT programmes. There is no universal consensus for this practice in children. We report our endoscopic experience in children with end-stage liver disease (ESLD) pre-LT. METHODS Retrospective audit of LT database and review of OGD findings of patients who had undergone endoscopy preceding LT. RESULTS Of 69 patients with ESLD, 50 (72.4%) had pre-LT OGD, 37 of which were done electively, whereas the remaining 13 were event driven. Forty-eight (96%) patients who underwent OGD had abnormalities, in which 38 (76%) patients had varices and 23 (46%) had portal hypertensive gastropathy. Eleven (22%) patients required therapeutic intervention at initial OGD either with endoscopic variceal band ligation or endoscopic sclerotherapy. Compared with the group who underwent elective OGDs, the group who had event-driven OGDs had a significantly higher requirement for endoscopic intervention (P

Purpose The understanding of the HRQOL issues for parent donors of children who underwent LDLT is lacking. We evaluated the HRQOL of donor and non-donor parents, described their subjective experiences and identified factors associated with lower HRQOL post-donation. Methods This is a cross-sectional study of parent donors whose children underwent LDLT, using SF-36v2 Health Survey to measure HRQOL, and a self-developed questionnaire to evaluate their subjective experiences. Results Of 32 pairs of donor and non-donor parents, 27 donor and 19 non-donor parents responded. The data of respondents were analyzed. Both donor and non-donor parents' SF-36v2 norm-based scores were average or above average as compared to the Singapore population. Donors who made lifestyle changes post-donation (adopting a healthy balanced diet, regular physical activity, quitting smoking, and moderate alcohol intake) were associated with lower GH (P = 0.009) and PF (P = 0.002) scores. Donors who took more than 3 months for full recovery had lower RP (P = 0.022) and BP scores (P = 0.038). On multivariate analysis, recipient complication of Clavien grade 3 or 4 was associated with increased RP score by 8.71 points (95% CI: 1.74-15.68), after adjusting for time taken for full recovery. Majority (88.8%) had self-reported recovery time under 6 months and returned to work within 3 months (74.0%). Conclusions Donors with factors potentially associated with lower HRQOL may need more support to ensure better HRQOL outcomes post-donation.

Background: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis – inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children. Methods: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia. Results: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived. Conclusions: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease. Key Words: sclerosing cholangitis, ulcerative colitis, progressive

The published paediatric experience with endoscopic retrograde cholangio-pancreatography (ERCP) in the diagnosis and management of biliary complications following liver transplantation (LT) is limited. We describe our experience with ERCP in the management of children following LT who presented with biliary complications, over a 20-year period (1995-2014). The retrospectively reviewed data are summarized descriptively. Of 94 children (47 boys) who received 102 liver transplants at our centre, seven children (five boys, two girls) underwent ERCP after liver transplantation. In total, 25 ERCP procedures were carried out in these patients. The median age at liver transplantation was 10.7 (3.9-16.2) years. The median interval between LT and the first ERCP was 28 days (12 days-6.8 years). All patients were on standard calcineurin-inhibitor-based immunosuppression regimens. Six of the seven patients underwent ERCP on more than one occasion [median number of ERCP sessions per patient- 4, (1-6)]. Seventeen procedures were carried out under conscious sedation, remaining eight under general anaesthesia. Sedation was achieved employing a standard regimen (Midazolam 5 mg with Pethidine 50 mg) and occasionally Fentanyl. ERCP is an effective and safe intervention from both diagnostic and therapeutic point of view, in the management of post-LT biliary complications in children.

A 19-year-old girl underwent renal transplantation for endtage renal disease. She had been Epstein–Barr virus (EBV)-naive re-transplant and seroconverted 15 months later but had been ell. Persistent epigastric pain despite treatment of Helicobacter ylori-associated gastritis necessitated a CT scan, which revealed ultiple hypodense liver lesions (segments 4a, 4b, 5) with the argest one measuring 5.1 cm by 5.8 cm with multiple nodular esions up to 11 mm in the spleen. F-18 FDG PET/CT scans conrmed these (Fig. 1A). EBV viral load measured by quantitative PCR as persistently high. Subsequent PET/CT scan revealed nodular esions in the lungs suggestive of pulmonary involvement (Fig. 1B). Targeted biopsy of the largest of the hepatic lesions revealed itotically inactive spindle-shaped cells, atypical hyperchromatic uclei and eosinophilic cytoplasm with strong diffuse positive taining with H & E (Fig. 2A) and EBER-ISH (Fig. 2B). This confirmed he diagnosis of EBV-associated smooth muscle tumour.

Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients.

In this paper, we present a tool, called Lego, which recovers object-oriented software architecture from stripped binaries. Lego takes a stripped binary as input, and uses information obtained from dynamic analysis to (i) group the functions in the binary into classes, and (ii) identify inheritance and composition relationships between the inferred classes. The information obtained by Lego can be used for reengineering legacy software, and for understanding the architecture of software systems that lack documentation and source code. Our experiments show that the class hierarchies recovered by Lego have a high degree of agreement---measured in terms of precision and recall---with the hierarchy defined in the source code.