Displaying publications 1 - 20 of 23 in total

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  1. Lee WS, Ng RT, Chan KW, Lau YL
    World J Gastroenterol, 2016 Dec 28;22(48):10653-10662.
    PMID: 28082818 DOI: 10.3748/wjg.v22.i48.10653
    AIM: Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD.

    METHODS: All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn's disease (CD).

    RESULTS: Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified.

    CONCLUSION: The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

  2. Lee WS, Teo KM, Ng RT, Chong SY, Kee BP, Chua KH
    Gene, 2016 Jul 15;586(1):1-6.
    PMID: 27050310 DOI: 10.1016/j.gene.2016.03.049
    Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder that is classically associated with intractable diarrhea with an onset within the first few months of life. Herein, we investigated and reported novel mutations in two causal genes in 3 Malaysian cases. Genomic DNA was extracted from peripheral blood obtained from patients in two Malaysian Chinese families. The exons of SKIV2L and TTC37 genes were amplified and sequenced by bi-directional sequencing to identify the point mutations within the coding sequence. Three Chinese boys from two families with characteristic features and clinical course were diagnosed with THES. In family-1, two point mutations were identified in the SKIV2L gene (c.1891G>A and c.3187C>T). In family-2, a single-nucleotide duplication (c.3426dupA) was found in the TTC37 gene. These mutations cause the production of abnormal non-functional gene product leading to the clinical manifestations in the patients. We reported three point mutations, which have not been previously described in other patients with THES in SKIV2L and TTC37 genes, including one nonsense, one frameshift, and one missense mutations.
  3. Lee WS, Ong SY, Foo HW, Wong SY, Kong CX, Seah RB, et al.
    World J Gastroenterol, 2017 Nov 21;23(43):7776-7784.
    PMID: 29209118 DOI: 10.3748/wjg.v23.i43.7776
    AIM: To examine the medical status of children with biliary atresia (BA) surviving with native livers.

    METHODS: In this cross-sectional review, data collected included complications of chronic liver disease (CLD) (cholangitis in the preceding 12 mo, portal hypertension, variceal bleeding, fractures, hepatopulmonary syndrome, portopulmonary hypertension) and laboratory indices (white cell and platelet counts, total bilirubin, albumin, international normalized ratio, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase). Ideal medical outcome was defined as absence of clinical evidence of CLD or abnormal laboratory indices.

    RESULTS: Fifty-two children [females = 32, 62%; median age 7.4 years, n = 35 (67%) older than 5 years] with BA (median age at surgery 60 d, range of 30 to 148 d) survived with native liver. Common complications of CLD noted were portal hypertension (40%, n = 21; 2 younger than 5 years), cholangitis (36%) and bleeding varices (25%, n = 13; 1 younger than 5 years). Fifteen (29%) had no clinical complications of CLD and three (6%) had normal laboratory indices. Ideal medical outcome was only seen in 1 patient (2%).

    CONCLUSION: Clinical or laboratory evidence of CLD are present in 98% of children with BA living with native livers after hepatoportoenterostomy. Portal hypertension and variceal bleeding may be seen in children younger than 5 years of age, underscoring the importance of medical surveillance for complications of BA starting at a young age.

  4. Chan KJ, Song ZL, Chew KS, Ng RT, Mohd Taib SH, Lee WS
    J Paediatr Child Health, 2021 Feb;57(2):239-245.
    PMID: 32936506 DOI: 10.1111/jpc.15184
    AIM: We aimed to ascertain the efficacy and feasibility of exclusive enteral nutrition (EEN) as an induction and re-induction therapy in Asian children with Crohn's disease (CD).

    METHODS: All children diagnosed with CD between 1995 and 2019 were reviewed. Response to induction was compared between EEN and standard immunosuppression (IS) using Paediatric Crohn's Disease Activity Index, growth failure, perianal disease and extra-intestinal manifestations. Two study groups were analysed: (i) primary induction and (ii) re-induction for relapses.

    RESULTS: Twenty-nine children (mean age (± standard deviation) at diagnosis 9.4 ± 8.5 years old, ileo-colonic 35%, non-stricturing 79%) were studied. At primary induction (group 1; n = 18), no difference was observed in remission rates (9/13 vs. 5/5; P = 0.278), efficacy for improving growth failure (6/8 vs. 0/1; P > 0.999), perianal disease (4/6 vs. 0/2; P > 0.999) and extra-intestinal manifestations (2/2 vs. 0/0; P > 0.999) with EEN or standard IS. Group 2 (n = 38 relapses), no difference was observed in remission rates (16/19 vs. 15/19, P > 0.999), growth failure (0/7 vs. 4/14; P = 0.328), perianal disease (1/10 vs. 7/7; P > 0.999) and extra-intestinal manifestations (0/0 vs. 1/1; P > 0.999) with EEN or standard IS. Both treatment modalities were equally effective as re-induction in relapses in patients previously treated with EEN (P = 0.191).

    CONCLUSION: As compared to standard IS, EEN was equally effective in primary induction and re-induction for relapse in Asian children with CD and can be repeatedly used for recurrent relapses.

  5. Ng RT, Lee WS, Ang HL, Teo KM, Yik YI, Lai NM
    Cochrane Database Syst Rev, 2016 Jul 05;7:CD010873.
    PMID: 27378432 DOI: 10.1002/14651858.CD010873.pub2
    BACKGROUND: Childhood constipation is a common problem with substantial health, economic and emotional burdens. Existing therapeutic options, mainly pharmacological, are not consistently effective, and some are associated with adverse effects after prolonged use. Transcutaneous electrical stimulation (TES), a non-pharmacological approach, is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall.

    OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.

    SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .

    SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.

    DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.

    MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (

    QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (

    QUALITY OF EVIDENCE: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (

    QUALITY OF EVIDENCE: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (

    QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (

    QUALITY OF EVIDENCE: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (QUALITY OF EVIDENCE for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.

    AUTHORS' CONCLUSIONS: The very low quality evidence gathered in this review does not suggest that TES provides a benefit for children with chronic constipation. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.

  6. Lee WS, Jalaludin MY, Wong SY, Ong SY, Foo HW, Ng RT
    Pediatr Neonatol, 2019 02;60(1):12-18.
    PMID: 29680189 DOI: 10.1016/j.pedneo.2018.03.011
    BACKGROUND: To determine vitamin D status in children with chronic liver disease (CLD) in a tropical country.

    METHODS: Cross-sectional study in Malaysian children with CLD. Factors affecting serum vitamin D level (definition: deficient 

  7. Lee WS, Song ZL, Em JM, Chew KS, Ng RT
    Pediatr Neonatol, 2021 05;62(3):249-257.
    PMID: 33546933 DOI: 10.1016/j.pedneo.2021.01.002
    BACKGROUND: Primary endoscopic prophylaxis in pediatric gastroesophageal varices is not universally practiced. We aimed to determine the role of primary endoscopic prophylaxis in preventing variceal bleeding in gastroesophageal varices in children.

    METHODS: We reviewed all children with gastroesophageal varices seen in our unit from 2000 to 2019. Primary prophylaxis was defined as endoscopic procedure without a preceding spontaneous bleeding and secondary prophylaxis as preceded by spontaneous bleeding. High-risk varices were defined as presence of grade III esophageal varices, cardia gastric varices or cherry red spots on the varices. Outcome measures (spontaneous rebleeding within 3 months after endoscopic procedure, number of additional procedures to eradicate varices, liver transplant [LT], death) were ascertained.

    RESULTS: Sixteen of 62 (26%) patients (median [± S.D.] age at diagnosis = 5.0 ± 4.3 years) with varices had primary prophylaxis, 38 (61%) had secondary prophylaxis while 8 (13%) had no prophylaxis. No difference in the proportion of patients with high-risk varices was observed between primary (88%) and secondary (92%; P = 0.62) prophylaxis. As compared to secondary prophylaxis, children who had primary prophylaxis were significantly less likely to have spontaneous rebleeding (6% vs. 38%; P = 0.022) and needed significantly fewer repeated endoscopic procedures (0.9 ± 1.0 vs. 3.1 ± 2.5; P = 0.021). After 8.9 ± 5.5 years of follow-up, overall survival was 85%; survival with native liver was 73%. No statistical difference was observed in the eventual outcome (alive with native liver) between primary and secondary (71% vs. 78%, P = 0.78).

    CONCLUSION: Children with PHT who had primary prophylaxis had less subsequent spontaneous rebleeding and needed fewer additional endoscopic procedures as compared to secondary prophylaxis but did not have an improved eventual outcome. Screening endoscopy in all children who have signs of PHT and primary prophylaxis in high-risk esophageal varices should be considered before eventual LT.

  8. Lee WS, Azmi N, Ng RT, Ong SY, Ponnampalavanar SS, Mahadeva S, et al.
    Intest Res, 2017 Oct;15(4):524-528.
    PMID: 29142521 DOI: 10.5217/ir.2017.15.4.524
    Anti-tumor necrosis factor (anti-TNF) is highly effective in inflammatory bowel disease (IBD); however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years). All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia). All 3 patients died within 1 year from the onset of the infection(s). We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.
  9. Ng RT, Lee WS, Ang HL, Teo KM, Yik YI, Lai NM
    Cochrane Database Syst Rev, 2016 11 11;11:CD010873.
    PMID: 27841439
    BACKGROUND: Childhood constipation is a common problem with substantial health, economic and emotional burdens. Existing therapeutic options, mainly pharmacological, are not consistently effective, and some are associated with adverse effects after prolonged use. Transcutaneous electrical stimulation (TES), a non-pharmacological approach, is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall.

    OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.

    SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .

    SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.

    DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes. We evaluated the overall quality of the evidence supporting the outcomes assessed in this review using the GRADE criteria.

    MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.We are very uncertain about the effects of TES on bowel movements, colonic transit, soiling symptoms and quality of life due to high risk of bias, indirectness and imprecision. For our outcomes of interest the 95% CI of most analysis results include potential benefit and no effect. There is insufficient evidence to determine the effect of TES on bowel movements and colonic transit. The study reported that 16/21 children in the TES group and 15/21 in the sham group had > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53; very low-quality evidence). Ten out of 14 children in the TES group had improved colonic transit compared to 1/7 in the sham group (RR 5.00, 95% CI 0.79 to 31.63; very low-quality evidence). Mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants; very low-quality evidence). The radiological assessment of colonic transit outcomes means that these results might not translate to important improvement in clinical symptoms or increased bowel movements. There is insufficient evidence to determine the effect of TES on symptoms and quality of life (QoL) outcomes. Nine out of 13 children in the TES group had improved soiling-related symptoms compared to 4/12 sham participants (RR 2.08, 95% CI 0.86 to 5.00; very low-quality evidence). Four out of 8 TES participants reported an improvement in QoL compared to 1/8 sham participants (RR 4.00, 95% CI 0.56 to 28.40; very low-quality evidence). The effects of TES on self-perceived (MD 5.00, 95% CI -1.21 to 11.21; one study, 33 participants; very low-quality evidence) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants; very low-quality evidence) are uncertain. No adverse effects were reported in the included study.

    AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.

  10. Ng RT, Lee WS, Ang HL, Teo KM, Yik YI, Lai NM
    Cochrane Database Syst Rev, 2016 Oct 12;10(10):CD010873.
    PMID: 27732736
    BACKGROUND: Childhood constipation is a common problem with substantial health, economic and emotional burdens. Existing therapeutic options, mainly pharmacological, are not consistently effective, and some are associated with adverse effects after prolonged use. Transcutaneous electrical stimulation (TES), a non-pharmacological approach, is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall.

    OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.

    SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .

    SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.

    DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.

    MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (Quality of evidence: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (Quality of evidence: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (Quality of evidence: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (Quality of evidence for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.

    AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.

  11. Lee WS, Chew KS, Ng RT, Kasmi KE, Sokol RJ
    Hepatol Int, 2020 May;14(3):305-316.
    PMID: 32356227 DOI: 10.1007/s12072-020-10048-8
    Premature infants and children with intestinal failure (IF) or short bowel syndrome are susceptible to intestinal failure-associated liver disease (IFALD, previously referred to as parenteral nutrition-associated liver disease, or PNALD). IFALD in children is characterized by progressive cholestasis and biliary fibrosis, and steatohepatitis in adults, and is seen in individuals dependent upon prolonged administration of PN. Many factors have been proposed as contributing to the pathogenesis of IFALD. In recent years, the focus has been on the potential synergistic roles of the intestinal microbiome, increased intestinal permeability, activation of hepatic innate immune pathways, and the use of intravenous soybean-oil-based intravenous lipid emulsions (SO-ILE). In vitro and in vivo studies have identified stigmasterol, a component of the plant sterols present in SO-ILE, as playing an important role. Although various strategies have been adopted to prevent or reverse IFALD, most suffer from a lack of strong evidence supported by well-designed, prospective clinical trials with clearly defined endpoints. Reduction in the amount of SO-ILEs or replacement with non-SO-ILEs has been shown to reverse IFALD although safety and long-term effectiveness have not been studied. Medical and surgical modalities to increase intestinal adaptation, advance enteral feedings, and prevent central line bloodstream infections are also important preventative strategies. There is a continued need to conduct high-quality, prospective trials with clearly define outcome measures to ascertain the potential benefits of these strategies.
  12. Lee WS, Lum SH, Lim CB, Chong SY, Khoh KM, Ng RT, et al.
    Hepatol Int, 2015 Apr;9(2):292-302.
    PMID: 25788179 DOI: 10.1007/s12072-014-9558-0
    BACKGROUND: Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population.

    METHODS: Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia.

    RESULTS: At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012].

    CONCLUSIONS: Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.
  13. Lee WS, Karthik SV, Ng RT, Ong SY, Ong C, Chiou FK, et al.
    Pediatr Neonatol, 2019 08;60(4):396-404.
    PMID: 31409456 DOI: 10.1016/j.pedneo.2018.09.007
    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.

  14. Lee WS, Tee CW, Koay ZL, Wong TS, Zahraq F, Foo HW, et al.
    World J Gastroenterol, 2018 Mar 07;24(9):1013-1021.
    PMID: 29531465 DOI: 10.3748/wjg.v24.i9.1013
    AIM: To study implications of measuring quality indicators on training and trainees' performance in pediatric colonoscopy in a low-volume training center.

    METHODS: We reviewed retrospectively the performance of pediatric colonoscopies in a training center in Malaysia over 5 years (January 2010-December 2015), benchmarked against five quality indicators: appropriateness of indications, bowel preparations, cecum and ileal examination rates, and complications. The European Society of Gastrointestinal Endoscopy guideline for pediatric endoscopy and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition training guidelines were used as benchmarks.

    RESULTS: Median (± SD) age of 121 children [males = 74 (61.2%)] who had 177 colonoscopies was 7.0 (± 4.6) years. On average, 30 colonoscopies were performed each year (range: 19-58). Except for investigations of abdominal pain (21/177, 17%), indications for colonoscopies were appropriate in the remaining 83%. Bowel preparation was good in 87%. One patient (0.6%) with severe Crohn's disease had bowel perforation. Cecum examination and ileal intubation rate was 95% and 68.1%. Ileal intubation rate was significantly higher in diagnosing or assessing inflammatory bowel disease (IBD) than non-IBD (72.9% vs 50.0% P = 0.016). Performance of four trainees was consistent throughout the study period. Average cecum and ileal examination rate among trainees were 97% and 77%.

    CONCLUSION: Benchmarking against established guidelines helps units with a low-volume of colonoscopies to identify area for further improvement.

  15. Chew KS, Em JM, Koay ZL, Jalaludin MY, Ng RT, Lum LCS, et al.
    Pediatr Neonatol, 2021 01;62(1):49-54.
    PMID: 32891528 DOI: 10.1016/j.pedneo.2020.08.009
    BACKGROUND: Functional gastrointestinal disorders (FGIDs) are common in children. The prevalence of FGIDs varies across the world but is unknown in Malaysia. We aimed to investigate the prevalence of FGIDs in healthy Malaysian infants.

    METHODS: This was a cross-sectional study involving healthy infants younger than 12 months of age who attended a well-baby clinic. A universal sampling method was adopted. Children with congenital disorders potentially affecting gastrointestinal functions, chronic debilitating diseases and hypothyroidism were excluded. Rome IV criteria were used to define FGIDs.

    RESULTS: Of the total 534 infants recruited (54% males), 92% were born at term; 85% had normal birth weight [range 2.5-4.0 kg], and the mean (±S.D.) age at interview was 6.8 (±3.4) months. Thirty-six percent were breastfed, 29% were formula-fed, and 35% had mixed feeding. Prevalence of infant regurgitation and rumination syndrome was 10.5% and 1.7%, respectively. Prevalence of infant colic was 1.9% (3/160) (infant 

  16. Ong F, Seah Lee W, Lin C, Ng RT, Yee Wong S, Lim SL, et al.
    Pediatr Neonatol, 2018 10;59(5):494-500.
    PMID: 29352665 DOI: 10.1016/j.pedneo.2017.12.007
    BACKGROUND: The use of complementary and alternative medicine (CAM) has been associated with adverse effects and self-imposed dietary restrictions. The prevalence of its use in Asian children with inflammatory bowel disease (IBD) is unknown. We aimed to determine the prevalence, types, and factors associated with the use of CAM among children with IBD from Singapore and Malaysia, and to ascertain if dietary restriction was prevalent in patients who used CAM.
    METHODS: A cross-sectional study was conducted in which parents of children with IBD attending two tertiary pediatric IBD referral centres in Singapore and Malaysia were interviewed. Data about demographics, conventional treatment, complementary therapies and dietary patterns were collected in a questionnaire.
    RESULTS: Of 64 children with IBD interviewed, 83% (n = 53) reported the use of CAM (Singapore [90%] vs. Malaysia [76%]; p = 0.152). The median number of CAM agents used was two (range 1-10). The three most common types of CAM used were probiotics (64%), vitamin and mineral supplements (55%), and food-based therapies (36%). Among individual CAM categories, the use of food-based therapies was correlated significantly with nationality (r = 0.497, p 
  17. Simovic I, Hilmi I, Ng RT, Chew KS, Wong SY, Lee WS, et al.
    United European Gastroenterol J, 2024 Feb;12(1):103-121.
    PMID: 37837511 DOI: 10.1002/ueg2.12477
    BACKGROUND: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.

    OBJECTIVES: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.

    METHODS: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model.

    RESULTS: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003).

    CONCLUSIONS: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.

  18. Ng RT, Chew KS, Choong CL, Song ZL, Teh JKL, Koay ZL, et al.
    Hepatol Int, 2022 Dec;16(6):1390-1397.
    PMID: 36131224 DOI: 10.1007/s12072-022-10417-5
    OBJECTIVE: Outcome of pediatric acute liver failure (PALF) in countries with limited availability of LT is not well described. We evaluated the outcome and prognostic indicators of PALF in Malaysia where emergency LT for ALF is limited.

    METHODS: In this retrospective review on children  452 μmol/L and peak GGT 

  19. Muhardi L, Aw MM, Hasosah M, Ng RT, Chong SY, Hegar B, et al.
    Front Pediatr, 2021;9:778747.
    PMID: 35071132 DOI: 10.3389/fped.2021.778747
    Regurgitation, colic, and constipation are frequently reported Functional Gastrointestinal Disorders (FGIDs) in the first few years of life. In 2016, the diagnostic criteria for FGIDs were changed from ROME III to ROME IV. This review assesses the prevalence of the most frequent FGIDs (colic, regurgitation and constipation) among children aged 0-5 years after the introduction of the later criteria. Articles published from January 1, 2016 to May 1, 2021 were retrieved from PubMed and Google Scholar using relevant keywords. A total of 12 articles were further analyzed based on the inclusion and exclusion criteria. This review consists of two studies (17%) from the Middle East, three (25%) from Asia, two (17%) from the USA, three (25%) from Europe, and one (8%) from Africa. Three studies (25%) were based on data obtained from healthcare professionals, while the rest were parent or caregiver reports. About half of the retrieved studies used the ROME IV criteria. Among infants aged 0-6 months, the reported prevalence of colic ranged between 10-15%, whilst that of regurgitation was 33.9%, and constipation was 1.5%. Among infants aged 0-12 months, the reported prevalence of regurgitation and constipation were 3.4-25.9% and 1.3-17.7%, respectively. The reported prevalence of constipation was 1.3-26% among children aged 13-48 months and 13% among children aged 4-18 years. Despite the large variations due to differences in diagnostic criteria, study respondents and age group, the prevalence of infantile colic was higher, while that for infantile regurgitation and constipation were similar using the ROME IV or III criteria.
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