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We report a case of junctional epidermolysis bullosa with pyloric atresia (JEB-PA) with minimal skin involvement but severe protein-losing enteropathy and airway involvement. Genetic analysis revealed heterozygous mutations in the ITGB4 gene encoding integrin β4 protein. Parental testing confirmed inheritance of frameshift variant (c.794dupC) as maternal and splice site variant (c.1608C>T/p.Cys536Cys) as paternal. Immunofluorescence mapping of her skin revealed a subepidermal blister with decreased and frayed integrin β4 at both the floor and the roof of the blister, while the intestinal mucosa showed complete absence of integrin β4. We review the literature and discuss the differential expression of integrins in the skin and gastrointestinal tract, as well as the role of chronic inflammation in the pathogenesis of EB.

Although IKK-β has previously been shown as a negative regulator of IL-1β secretion in mice, this role has not been proven in humans. Genetic studies of NF-κB signaling in humans with inherited diseases of the immune system have not demonstrated the relevance of the NF-κB pathway in suppressing IL-1β expression. Here, we report an infant with a clinical pathology comprising neutrophil-mediated autoinflammation and recurrent bacterial infections. Whole-exome sequencing revealed a de novo heterozygous missense mutation of NFKBIA, resulting in a L34P IκBα variant that severely repressed NF-κB activation and downstream cytokine production. Paradoxically, IL-1β secretion was elevated in the patient’s stimulated leukocytes, in her induced pluripotent stem cell–derived macrophages, and in murine bone marrow–derived macrophages containing the L34P mutation. The patient’s hypersecretion of IL-1β correlated with activated neutrophilia and liver fibrosis with neutrophil accumulation. Hematopoietic stem cell transplantation reversed neutrophilia, restored a resting state in neutrophils, and normalized IL-1β release from stimulated leukocytes. Additional therapeutic blockade of IL-1 ameliorated liver damage, while decreasing neutrophil activation and associated IL-1β secretion. Our studies reveal a previously unrecognized role of human IκBα as an essential regulator of canonical NF-κB signaling in the prevention of neutrophil-dependent autoinflammatory diseases. These findings also highlight the therapeutic potential of IL-1 inhibitors in treating complications arising from systemic NF-κB inhibition. Refereed/Peer-reviewed

The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow's milk protein allergy (CMPA) and lactose intolerance (LI) in infants.A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) disease-specific knowledge and potential educational needs.Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area.The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

AIM Central line-associated bloodstream infection associated bloodstream infection (CLABSI) is a serious complication of patients on central venous catheters (CVC). Taurolidine-citrate solution (TCS) is a catheter-lock solution with broad-spectrum antimicrobial action. This study's aim was to evaluate the efficacy of TCS in reducing CLABSI rates in paediatric haematology-oncology (H/O) and gastrointestinal (GI) patients with long-term CVC. METHODS This was an open-label trial of H/O and GI inpatients with the following inclusion criteria

Background Exclusive enteral nutrition (EEN) is as effective as corticosteroids in inducing remission in children with Crohn’s disease (CD). However, over 50% of these children relapse by 12 months of diagnosis. Thiopurines are commonly prescribed as maintenance therapy for CD, but evidence for its efficacy is controversial. Data on the effectiveness of EEN in Southeast Asian (SEA) children with CD is scarce. This study aims to evaluate the efficacy of EEN induction therapy in a cohort of SEA children with newly diagnosed CD. The secondary aim was to evaluate concomitant early azathioprine (EAZ) use in determining remission rate at 6 and 12 months. Methods Case records of all children with newly diagnosed CD from 2011 to 2014 were reviewed and relevant demographic as well as clinical data were extracted. The primary outcome measure was the number of patients who completed EEN induction therapy and achieved remission (Paediatric Crohn’s Disease Activity Index; PCDAI≤10). Factors influencing duration of remission were evaluated in particular early azathioprine (EAZ) defined as starting azathioprine within one month of diagnosis versus late azathioprine (LAZ) use. Results Forty children with newly diagnosed CD were identified. Thirty-three children: 67% boys, median age 13y (range 3–17) completed 8 weeks of EEN induction therapy and 91% achieved remission. Significant improvements were seen in PCDAI scores (32.7 ± 9.2 to 4.2 ± 5.1; p

Aim We compared the vaccine effectiveness of monovalent and combination hepatitis B vaccine regimens in infants born to chronic hepatitis B carrier mothers. Methods An observational cohort of neonates was recruited over 78 months from two public hospital maternity units in Singapore. We enrolled term infants, born to chronic hepatitis B surface antigen-positive mothers regardless of their hepatitis Be antigen status, who completed the hepatitis B virus (HBV) vaccination programme in Singapore. Infants born to mothers on antiviral therapy, or with concurrent hepatitis C or human immunodeficiency virus infection were excluded. All infants received hepatitis B immunoglobulin at birth. One group received three doses of monovalent hepatitis B vaccine (0, 1, 6 months) (regimen A). The other group received two doses of monovalent vaccine, followed by one dose combination vaccine DTaP-IPV-Hib-HBV (0, 1, 6 months) (regimen B). Vaccine effectiveness was determined by immunoprophylaxis failure leading to HBV vertical transmission. Immunogenicity was assessed by hepatitis B surface antibody (anti-HBs) levels at 9 months of age. Results Total of 177 term neonates received regimen A and 115 received regimen B. Immunoprophylaxis failure rate was low, 2.3 and 2.6% (P = 1.00) in regimen A and B, respectively. Mean anti-HBs titres were similar at 643 ± 374 and 561 ± 396 IU/L (P = 0.08) for regimen A and B, respectively. Conclusion Hepatitis B vaccine regimens using monovalent or combination vaccine for the third dose showed similarly high vaccine effectiveness and low immunoprophylaxis failure rate in term infants born to chronic hepatitis B carrier mothers.

OBJECTIVES Epidemiological studies on pediatric-onset inflammatory bowel disease (PIBD) are scarce in South-East Asia (SEA). This study aimed to evaluate the incidence trend and clinical characteristics of PIBD in a SEA cohort in Singapore over 22 years (1994-2015). METHODS Case records of PIBD ≤18 years from the only two tertiary pediatric hospitals in Singapore were reviewed. The mean annual incidence (MAI) of PIBD was calculated based on Singapore's age-specific population data. RESULTS Overall MAI of PIBD was 1.26 per 100 000 (95% confidence interval [CI] 0.56-1.96). During the first decade (1994-2004) MAI was 0.23 per 100 000 (95% CI 0.08-0.39); this rose almost 10-fold to 2.28 per 100 000 (95% CI 1.15-3.41) during the second decade (2005-2015). Linear regression analysis showed significant increase in MAI over the 22-year period (r = 0.826, P

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

Aiming to explore factors affecting Malaysian Chinese parents in sending their children to either national secondary schools or Chinese independent schools, 494 parents were surveyed using ...

Aim Biliary atresia (BA) has preponderance in Asian populations with Kasai portoenterostomy (KP) regarded as the first-line standard of care. Yet reports from Southeast Asia remain scant. This study reviews the demographics, short- and medium-term outcomes for our cohort, and evaluates prognostic factors for outcome. Methods All patients diagnosed with BA between January 1997 and December 2013 were included. Clinical data were obtained from medical records. Jaundice clearance was defined as total bilirubin

BACKGROUND/AIM: : Portal hypertension and variceal hemorrhage (VH) are significant complications in biliary atresia (BA). The study aims to evaluate risk factors and noninvasive markers that predict actual VH for the first time in children with BA without prior endoscopic surveillance or treatment. METHODS: Retrospective review was performed of patients diagnosed with BA from 1989 to 2016 at a single center. Primary outcome was the first episode of VH. Patients were stratified into VH and non-VH groups according to the development of VH, and laboratory and ultrasonographic data were analyzed at 2 time points: pre-VH and the last follow-up. Existing indices, varices prediction rule (VPR), and aspartate aminotransferase (AST)–platelet ratio index (APRI) were also applied retrospectively to evaluate their performance in prediction of VH in our cohort. RESULTS: Seventy-two patients were included; 16 patients developed the first VH at median age of 5.5 years. On univariate analysis, serum albumin (P = 0.034), AST (P = 0.017), hemoglobin (P = 0.019), platelet count (P =

The association between inflammatory bowel disease and joint involvement is well established. There is a paucity of data describing histopathological features of the gut in relation to juvenile idiopathic arthritis (JIA).We retrospectively identified 33 (21 male) children aged 3-16 y with JIA (11 with oligoarthritis, 5 with polyarthritis, 8 with systemic onset arthritis, 8 with enthesitis-related arthritis (ERA), and 1 with psoriatic arthritis) with significant gastrointestinal (GI) symptoms who underwent upper and/or lower endoscopy. The histopathological findings were reviewed in addition to presence of autoantibodies and concomitant treatment.The most common GI indications for endoscopy were persistent abdominal pain (14/33 (42%)) and diarrhea (10/33 (30%)). Of the 33 children, 28 (85%) had gut mucosal inflammation, mostly affecting the colon (80%). Active inflammation of the gut was found in 5 of 28 (17%) children, and 15 of 28 (53%) children showed mild nonspecific inflammation. Eight patients (27%) had predominantly an eosinophilic infiltrate. Twenty-six patients had previously received treatment for JIA. There was a negative association with the use of immunomodulators and the presence of eosinophil inflammation.The majority of children with JIA and GI symptoms have histological evidence of mild nonspecific inflammation, but some having active colitis and prominent eosinophil infiltrate.

Background Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. Methods This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. Results The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). Conclusions Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

The Advisory Committee on Immunization Practices (ACIP) recommends a 4-dose vaccination schedule for preterm low birth weight infants (2 kg) and a 3-dose vaccination schedule for preterm infants (≥2 kg) born to hepatitis B surface antigen (HBsAg)-positive mothers. However, data remain limited for these high-risk infants, and the optimal dosing schedule in Asia is not well established.The aim of this study was to evaluate the serologic vaccine responses in preterm infants born to HBsAg-positive mothers using current vaccination guidelines.Preterm babies of gestation less than 37 completed weeks born to HBsAg-positive mothers were prospectively recruited during 6 years (June 2009 to December 2015) and retrospectively recruited via convenience sampling in 2 years (June 2013 to April 2015) in 2 tertiary pediatric centers. The preterm infants were given 4 or 3 vaccine doses as per ACIP 2005 guidelines. Vaccine response was defined as achieving hepatitis B surface antibody values of10 IU/L [Abbott Architect (Abbott Laboratories, Chicago, IL)] at 9 months of chronologic age.A total of 24 preterm infants were recruited. Four had a birth weight2 kg. Of 23 surviving infants, all were negative for HBsAg. One baby (4.5%) did not achieve adequate vaccine response. All 4 infants with birth weight2 kg achieved seroprotective values.The current ACIP-recommended vaccination schedule results in adequate antibody responses in preterm infants of HBsAg-positive mothers.

Epidemiological studies on pediatric-onset inflammatory bowel disease (PIBD) are scarce in South-East Asia (SEA). This study aimed to evaluate the incidence trend and clinical characteristics of PIBD in a SEA cohort in Singapore over 22 years (1994-2015).Case records of PIBD ≤18 years from the only two tertiary pediatric hospitals in Singapore were reviewed. The mean annual incidence (MAI) of PIBD was calculated based on Singapore's age-specific population data.Overall MAI of PIBD was 1.26 per 100 000 (95% confidence interval [CI] 0.56-1.96). During the first decade (1994-2004) MAI was 0.23 per 100 000 (95% CI 0.08-0.39); this rose almost 10-fold to 2.28 per 100 000 (95% CI 1.15-3.41) during the second decade (2005-2015). Linear regression analysis showed significant increase in MAI over the 22-year period (r = 0.826, P 0001). Of the 228 patients, 61.0% had Crohn's disease (CD), 30.3% ulcerative colitis and 8.7% IBD-unclassified, with a mdian age at diagnosis of 10.47 years and a male predominance (58.3%); 37.7% of them aged10 years at diagnosis and 17.5% were very early-onset IBD. In CD, 27.3% had stricturing and/or penetrating disease and 21.6% were with perianal disease. Indians had a disproportionately high representation while positive family history was rare (1.3%).Although PIBD is uncommon in Singapore, its incidence has risen dramatically over recent decades. A younger age of disease onset and higher proportions of perianal and stricturing/penetrating diseases suggest more aggressive disease than in Western data.

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 concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

Tricho-hepato-enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction. We report two cases of East Asian descent with THE-S who had remained undiagnosed despite extensive investigations but were diagnosed on whole exome sequencing (WES). Both cases presented with chronic diarrhea, failure to thrive, and recurrent infections. Case 1 had posteriorly rotated low set ears, mild retrognathia, and fine curly hypopigmented hair. She was managed with prolonged total parenteral nutrition and intravenous immunoglobulin infusions. Case 2 had sparse coarse brown hair as well as multiple lentigines and café-au-lait macules. She was managed with amino acid-based formula. For both cases, routine investigations were inconclusive. WES in both cases showed biallelic truncating mutations in TTC37 (c.3507TG;p.Y1169X and c.3601CT;p.R1201X in case 1 and c.3507TG;p.Y1169X and c.154GT;p.E52X in case 2), suggesting a diagnosis of THE-S.We present novel mutations in the TTC37 gene in two individuals of East Asian descent with the rare THE-S, detected by WES. Future identification of patients with THE-S and establishing genotype-phenotype correlations will aid in counseling the patients and their families.• Tricho-Hepato-Enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction. • Complex patients with diagnostic dilemmas undergo extensive investigations. What is New: • This is a report of novel mutations in TTC37 in individuals of East Asian descent. • Whole exome sequencing (WES) can be useful in certain complex cases with diagnostic dilemmas.

This study aims to examine whether different educational systems will impose students with different perception on Chinese values. Cluster sampling method was used and 599 Chinese students from three national secondary schools (NSS) and two Chinese independent schools (CIS) in Malaysia were recruited. A questionnaire containing two sections namely background information and Chinese value scale developed by Chinese Culture Connection (1987) was distributed. The findings showed that the practice of Chinese cultural values indicated through the use of Chinese language in everyday life between respondents from NSS and CIS is about the same, but more respondents from CIS read or watch Chinese materials than those from NSS. Respondents from CIS and NSS viewed integrity and tolerance as the most important Chinese value. Respondents from NSS perceived Confucians ethos or human relationship as more important, whereas respondents from CIS chose loyalty to ideals and humanity. The findings suggested that the role of parents in the perseverance of Chinese culture and the influence of different school environment are equally important in determining the perception of Chinese values among secondary school students.

It is widely claimed that many university students were found to be unprepared for the reading demands placed upon them. To provide students with an understanding of the features of the discourses they may encounter, this study investigates lexical bundles (LBs) used in the reading passages of Malaysian University English Test (MUET), a compulsory entrance examination for tertiary education. More specifically it aims to compare and contrast the functional types of LBs found in arts and science-based reading passages. A specialised corpus of MUET test papers made up of only the reading passages categorised into two main traditional disciplines; arts and science was built using WordSmith Tools Version 5. The lists of LBs of the identified disciplines were generated using WordSmith Tools Version 5. The generated data was then analysed qualitatively based on Hyland’s (2008) Functional Taxonomy. Findings revealed that although the number of LBs in both disciplines shows significant difference, many similar LBs are found. Science-based passages employ more research-based LBs whereas arts-based texts employ more participant-oriented LBs. These findings seemed to confirm that the functions of LBs are specific to particular disciplines. Hence, explicit teaching of LBs should be considered in schools and two separate sets of MUET reading tests where the first comprises of texts adopted from the scientific and technological context while the other made up of texts from the social sciences should be designed to accommodate both arts and science stream pre-university students. DOI: http://dx.doi.org/10.17576/GEMA-2015-1501-05

We compared the vaccine effectiveness of monovalent and combination hepatitis B vaccine regimens in infants born to chronic hepatitis B carrier mothers.An observational cohort of neonates was recruited over 78 months from two public hospital maternity units in Singapore. We enrolled term infants, born to chronic hepatitis B surface antigen-positive mothers regardless of their hepatitis Be antigen status, who completed the hepatitis B virus (HBV) vaccination programme in Singapore. Infants born to mothers on antiviral therapy, or with concurrent hepatitis C or human immunodeficiency virus infection were excluded. All infants received hepatitis B immunoglobulin at birth. One group received three doses of monovalent hepatitis B vaccine (0, 1, 6 months) (regimen A). The other group received two doses of monovalent vaccine, followed by one dose combination vaccine DTaP-IPV-Hib-HBV (0, 1, 6 months) (regimen B). Vaccine effectiveness was determined by immunoprophylaxis failure leading to HBV vertical transmission. Immunogenicity was assessed by hepatitis B surface antibody (anti-HBs) levels at 9 months of age.Total of 177 term neonates received regimen A and 115 received regimen B. Immunoprophylaxis failure rate was low, 2.3 and 2.6% (P = 1.00) in regimen A and B, respectively. Mean anti-HBs titres were similar at 643 ± 374 and 561 ± 396 IU/L (P = 0.08) for regimen A and B, respectively.Hepatitis B vaccine regimens using monovalent or combination vaccine for the third dose showed similarly high vaccine effectiveness and low immunoprophylaxis failure rate in term infants born to chronic hepatitis B carrier mothers.

Lactose is the main carbohydrate in human and mammalian milk. Lactose requires enzymatic hydrolysis by lactase into D-glucose and D-galactose before it can be absorbed. Term infants express sufficient lactase to digest about one liter of breast milk daily. Physiological lactose malabsorption in infancy confers beneficial prebiotic effects, including the establishment of Bifidobacterium-rich fecal microbiota. In many populations, lactase levels decline after weaning (lactase non-persistence; LNP). LNP affects about 70% of the world’s population and is the physiological basis for primary lactose intolerance (LI). Persistence of lactase beyond infancy is linked to several single nucleotide polymorphisms in the lactase gene promoter region on chromosome 2. Primary LI generally does not manifest clinically before 5 years of age. LI in young children is typically caused by underlying gut conditions, such as viral gastroenteritis, giardiasis, cow’s milk enteropathy, celiac disease or Crohn’s disease. Therefore, LI in childhood is mostly transient and improves with resolution of the underlying pathology. There is ongoing confusion between LI and cow’s milk allergy (CMA) which still leads to misdiagnosis and inappropriate dietary management. In addition, perceived LI may cause unnecessary milk restriction and adverse nutritional outcomes. The treatment of LI involves the reduction, but not complete elimination, of lactose-containing foods. By contrast, breastfed infants with suspected CMA should undergo a trial of a strict cow’s milk protein-free maternal elimination diet. If the infant is not breastfed, an extensively hydrolyzed or amino acid-based formula and strict cow’s milk avoidance are the standard treatment for CMA. The majority of infants with CMA can tolerate lactose, except when an enteropathy with secondary lactase deficiency is present. Keywords: Malabsorption, Carbohydrate, Enteropathy, Cow’s milk allergy, Celiac disease, Gastroenteritis

Background Parenteral nutrition (PN) is the mainstay of treatment in children with chronic intestinal failure. We review our experience in home parenteral nutrition and describe outcomes of long term home PN therapy. Methods A retrospective cohort study was conducted by retrieving clinical records of patients with primary digestive diseases who were on home parenteral nutrition between July 2014 to July 2016. Results 13 patients (4 boys, 9 girls) received PN for more than 2 months. Out of these, 8 patients required PN therapy for more than 6 months. Main indications for long-term PN included chronic intestinal pseudo-obstruction syndrome (CIPOS, 38%), short bowel syndrome (SBS, 54%) and inflammatory bowel disease (IBD, 8%). Median age for initiation of PN was 1.7 years. Median duration of PN therapy was 1.4 years. 6 patients (46%), all with SBS, were successfully weaned off PN. One of the major complications of long term PN was central line-associated bloodstream infection (CLABSI). Incidence of CLABSI was 5.3 per 1000 catheter days. After implementation of use of Taurolidine-citrate solution (TCS), a catheter-lock solution, incidence of CLABSI improved with a pre and post-TCS CLABSI rate ratio of 0.17 (95% CI 0.04–0.52, p Conclusions PN is a safe and crucial modality of treatment in children with chronic intestinal failure. SBS forms the largest subgroup in our paediatric intestinal failure population. However, patients in this subgroup were also more likely to be weaned off PN. Incidence of CLABSI can be effectively controlled with introduction of TCS. Incidence of IFALD can also be reduced with SMOF and other new lipids.

AIM To describe the etiology and characteristics of early-onset conjugated hyperbilirubinemia (ECHB) presenting within 14 d of life in term neonates. METHODS Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia (CHB) at a tertiary center over a 5-year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin (CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 μmol/L. ECHB is defined as CHB detected within 14 d of life. "Late-onset" CHB (LCHB) is detected at 15-28 d of life and served as the comparison group. RESULTS Total of 117 patients were recruited: 65 had ECHB, 52 had LCHB. Neonates with ECHB were more likely to be clinically unwell (80.0% vs 42.3%, P < 0.001) and associated with non-hepatic causes (73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury (75.0%) and sepsis (17.3%) were the most common causes of ECHB in clinically unwell infants, majority (87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare (5.8%) but associated with high mortality (100%) in our series. In the subgroup of clinically well infants (n = 13) with ECHB, biliary atresia (BA) was the most common diagnosis (61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB. CONCLUSION Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice.

Background: Dengue fever is common in Southeast Asia although liver failure is a rare complication with up to 50% mortality rate reported in children. Objective: To evaluate the characteristics and treatment outcome of dengue fever associated liver failure (DFALF) in a case series of 4 paediatric patients. DFALF was defined as INR>2, regardless of the presence or absence of encephalopathy or INR>1.5 not corrected by Vitamin K in the presence of clinical hepatic encephalopathy, during the course of concurrent dengue infection. Material and methods: Patients with DFALF, admitted to a tertiary paediatric centre in Singapore over a 6 year period (January 2009-December 2015) were identified from the Gastroenterology and Infectious Disease databases. Case records were retrospectively reviewed. Results: Four patients, all boys, age 5 months to 6 years, presented at the acute febrile phase of illness with Dengue Shock Syndrome (severe dengue). Aspartate Transaminase (AST) and Alanine Transaminase (ALT) peaked at day 4-7: median (± 2SD) peak ALT 1871.5 ± 917 u/L, whereas median peak AST 7802.5 ± 5453.8 u/L. Median peak International Normalised Ratio ( INR ), ammonia, lactate were 2.9 ± 1.6, 106 ± 144.6 umol/L, and 7.4 ± 8.4 mmol/L respectively. All patients had hepatomegaly and mild conjugated hyperbilirubinaemia, with median peak total bilirubin 73.5 ± 36.9 umol/L. Two patients received N-Acetylcysteine. One patient received intravenous dexamethasone for dengue associated hemophagocytic lymphohistiocytosis. All recovered fully with supportive treatment based on a well-designed acute liver failure protocol, which comprised of intensive care monitoring, correction of coagulopathy and hypoglycaemia, empirical broad spectrum antibiotic coverage and anti-fungal prophylaxis, gastrointestinal haemorrhage prophylaxis with a histamine-2 receptor antagonist, proton pump inhibitor or sucralfate, and lactulose to reduce hyperammonaemia. Liver function significantly improved (ALT

We herein report the case of a 14-year-old girl with Epstein-Barr virus (EBV) infectious mononucleosis who developed prolonged hepatitis and jaundice. At presentation, she had tender hepatomegaly with a markedly deranged liver function test. Abdominal ultrasonography showed hepatomegaly and a thickened gallbladder wall. During the subsequent 11 weeks, her transaminases showed two further peaks, which corresponded with clinical deterioration. Her highest alanine transaminase level was 1,795 µ/L and total bilirubin level was 154 µmol/L. She recovered fully with conservative management. EBV-related liver involvement is typically mild and self-limiting. We believe that tender hepatomegaly and gallbladder thickening may be important predictors of significant liver involvement. Although multiple transaminase peaks may occur, we do not consider this an indication for antiviral or immunosuppressive therapy. In the absence of strong evidence supporting the use of any specific therapy, we recommend a conservative approach for an immunocompetent patient.

Biliary atresia (BA) has preponderance in Asian populations with Kasai portoenterostomy (KP) regarded as the first-line standard of care. Yet reports from Southeast Asia remain scant. This study reviews the demographics, short- and medium-term outcomes for our cohort, and evaluates prognostic factors for outcome.All patients diagnosed with BA between January 1997 and December 2013 were included. Clinical data were obtained from medical records. Jaundice clearance was defined as total bilirubin20 µmol/L within 6 months after KP. Two-year and 5-year native liver survival (NLS) were determined. Prognostic factors examined included gender, ethnicity, associated anomalies, age at KP, post-KP cholangitis and clearance of jaundice within 6 months.Of 58 patients studied, 31(53.4%) were male. Median age at time of KP was 53 days (range: 28-127). Ethnic distribution showed 32 (55.2%) Chinese, 16 (27.6%) Malays and 10 (17.2%) others. Twenty-one (36.2%) patients achieved jaundice clearance by 6 months. Two-year NLS rate was 36 out of 50 (72%), while 5-year NLS rate was 16 out of 35 (45.7%). Only clearance of jaundice within 6 months had a significant association with NLS (P = 0.006). All other factors showed no significant impact on outcome.Our short- and medium-term outcomes after KP for BA are comparable with those reported by most international centres. However, prognostic factors such as age at KP, cholangitis episodes and associated anomalies did not show significant correlation; only clearance of jaundice within 6 months was significantly predictive of NLS.

Picky eating is a common cause of concern for parents of young children. Paediatricians and family physicians are in a key position to help parents learn ways to feed their children effectively. Despite the high prevalence of picky eating, the growth of the majority of picky eaters does not suffer adversely. In the absence of worrying signs and symptoms, reassurance of the child’s normal growth would help allay parental anxieties. Reinforcement of basic feeding principles and providing healthy dietary advice are important strategies to help parents manage children who are picky eaters.

Recurrent abdominal pain in childhood is common, and continues to be a diagnostic and therapeutic challenge. It is usually attributed to a functional gastrointestinal disorder rather than an organic disease. In most cases, a comprehensive history and physical examination should enable one to make a positive diagnosis of functional disorder. The presence of alarm symptoms and signs, such as weight loss, gastrointestinal bleeding and chronic severe diarrhoea, warrants further investigations and referral to a paediatric gastrointestinal specialist. The mainstay of therapy in functional abdominal pain is education, reassurance and avoidance of triggering factors. While symptom-based pharmacological therapy may be helpful in patients who do not respond to simple management, it is best used on a time-limited basis due to the lack of good evidence of its efficacy. The primary goal of therapy is a return to normal daily activities rather than complete elimination of pain. In recalcitrant cases, psychological interventions such as cognitive behaviour therapy and relaxation training have proven to be efficacious.

AIM: To evaluate the clinicopathological features and treatment outcomes of cap polyposis in the pediatric population. METHODS: All pediatric patients with histologically proven diagnosis of cap polyposis were identified from our endoscopy and histology database over a 12 year period from 2000-2012 at our tertiary pediatric center, KK Women’s and Children’s Hospital in Singapore. The case records of these patients were retrospectively reviewed. The demographics, clinical course, laboratory results, endoscopic and histopathological features, treatments, and outcomes were analyzed. The study protocol was approved by the hospital institutional review board. The histological slides were reviewed by a pediatric histopathologist to confirm the diagnosis of cap polyposis. RESULTS: Eleven patients were diagnosed with cap polyposis. The median patient age was 13 years (range 5-17 years); the sample included 7 males and 4 females. All of the patients presented with bloody stools. Seven patients (63%) had constipation, while 4 patients (36%) had diarrhea. All of the patients underwent colonoscopy and polypectomies (excluding 1 patient who refused polypectomy). The macroscopic findings were of polypoid lesions covered by fibrinopurulent exudates with normal intervening mucosa. The rectum was the most common involvement site (n = 9, 82%), followed by the rectosigmoid colon (n = 3, 18%). Five (45%) patients had fewer than 5 polyps, and 6 patients (65%) had multiple polyps. Histological examination of these polyps showed surface ulcerations with a cap of fibrin inflammatory exudate. Four (80%) patients with fewer than 5 polyps had complete resolution of symptoms following the polypectomy. One patient who did not consent to the polypectomy had resolution of symptoms after being treated with sulphasalazine. All 6 patients with multiple polyps experienced recurrence of bloody stools on follow-up (mean = 28 mo). CONCLUSION: Cap polyposis is a rare and under-recognised cause of rectal bleeding in children. Our study has characterized the disease phenotype and treatment outcomes in a pediatric cohort.

Urinary symptoms are well-described in children with chronic constipation which include enuresis, urgency and recurrent urinary infections. Renal tract obstruction is a rare complication of severe chronic constipation. We describe a case of a 10-year-old boy with a history of long-standing constipation who presented with obstructive uropathy. Treatment strategies involved intensive medical therapy, parental education, behaviour modification strategies and close follow-up in a specialised constipation clinic. The obstruction was reversed and medications were discontinued after six months. Successful management of children with chronic constipation involves a multi-disciplinary approach in a specialised constipation clinic.