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  1. Kotlarz D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, et al.
    Nat Genet, 2018 Mar;50(3):344-348.
    PMID: 29483653 DOI: 10.1038/s41588-018-0063-6
    Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis1,2. Following its discovery 3 , enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties4,5, pro- and anti-inflammatory effects 6 , or pro- and anti-fibrinogenic characteristics 7 . Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1-LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications*
  2. Hilmi I, Sunderesvaran K, Ananda V, Sarji SA, Arumugam K, Goh KL
    J Clin Endocrinol Metab, 2013 Jun;98(6):2415-21.
    PMID: 23553858 DOI: 10.1210/jc.2013-1147
    INTRODUCTION: Osteoporosis and osteopenia are well-recognized complications of inflammatory bowel disease. Previous studies have suggested that vitamin D deficiency is an important risk factor for the development of osteoporosis. We hypothesized that low vitamin D levels is the main reason for reduced bone mineral density in patients with inflammatory bowel disease. We aimed to study its potential role in Malaysia, which is a tropical country with 3 large ethnic groups. We also sought to examine the relationship between fracture risk and bone mineral density in this group.
    METHODOLOGY: Relevant history as well as 25-hydroxycholecalciferol (vitamin D) levels and bone mineral density were obtained. Normal, inadequate, and low vitamin D levels were defined as 61-160 nmol/L (24-64 ng/mL), 30-60 nmol/L (12-24 ng/mL), and less than 30 nmol/L (<12 ng/mL), respectively.
    RESULTS: Seventy-two patients were recruited. The prevalence of osteopenia and osteoporosis, respectively, were 58% and 17% in the spine and 51% and 14% in the hip. Mean vitamin D level in the group was low at 45.12 ± 17.4 nmol/L (18.05 ± 6.96 ng/mL), but there was no significant association between bone mineral density and vitamin D level. Twelve patients (16.7%) had a fragility fracture after the diagnosis of inflammatory bowel disease. The cumulative fracture incidence was 10% at 5 years and 35% at 10 years. There was a statistically significant association between osteoporosis of hip and a history of fracture (odds ratio 5.889; 95% confidence interval 1.41-24.53, P = .009).
    CONCLUSION: Osteoporosis is prevalent among Malaysian patients with inflammatory bowel disease and is associated with a 6-fold increased risk of fractures. Most inflammatory bowel disease patients had inadequate or low vitamin D levels, but there was no association between vitamin D levels and BMD.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications*
  3. Poh KS, Qureshi S, Hong YK, Moreno T, Stocchi L, Hull T, et al.
    Dis Colon Rectum, 2020 05;63(5):639-645.
    PMID: 32032200 DOI: 10.1097/DCR.0000000000001617
    BACKGROUND: Restorative total proctocolectomy with IPAA may not be feasible in some patients because of technical intraoperative limitations.

    OBJECTIVE: This study aimed to assess preoperative predictors for intraoperative IPAA and review management.

    DESIGN: This is a retrospective review.

    SETTING: This study was conducted at Cleveland Clinic between January 2010 and May 2018.

    PATIENTS: Patients ≥18 years of age who underwent ileoanal pouch surgery were included. Patients with successful pouch creation as planned were grouped as "successful IPAA creation." Operative reports of patients who underwent alternative procedures were reviewed to identify cases when the pouch was preoperatively planned but intraoperatively abandoned (IPAA-abandoned group). Multivariate logistic regression models were developed to determine predictors of intraoperative pouch abandonment. We also reviewed the management of patients in whom the initial pouch creation failed.

    MAIN OUTCOME MEASURES: The primary outcomes measured were preoperative predictors for intraoperative ileoanal pouch abandonment.

    RESULTS: A total of 1438 patients were offered an ileoanal pouch; 21 (1.5%) experienced pouch abandonment due to inadequate reach (n = 17) and other technical reasons (n = 4). These patients underwent alternative procedures such as end or loop ileostomy with/without proctectomy. Multivariate logistic regression analysis indicated male sex (OR, 6.021; 95% CI, 1.540-23.534), BMI (OR, 1.217; 95% CI, 1.114-1.329), and a 2-stage procedure (OR, 14.510; 95% CI, 4.123-51.064) as independent factors associated with intraoperative abandonment of pouch creation. Alternative procedures were total proctocolectomy with end ileostomy (n = 14) and total abdominal colectomy with end ileostomy without proctectomy (n = 7). Ultimately, pouch creation was achieved in 6 of 21 patients after a median interval of 8.8 (range, 4.1-34.8) months. All patients had intentional weight loss before a reattempt and total abdominal colectomy with end ileostomy without proctectomy as their initial procedure.

    LIMITATIONS: This study was limited by its retrospective nature.

    CONCLUSIONS: Ileoanal pouch abandonment is rare and can be mitigated by initial total abdominal colectomy and weight loss. Male, obese patients are at a higher risk of failure. Intraoperative assessment of ileoanal pouch feasibility should occur before rectal dissection. See Video Abstract at http://links.lww.com/DCR/B156. PREDICCIÓN MULTIVARIANTE DEL ABANDONO INTRAOPERATORIO DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL: La proctocolectomía total restaurativa con anastomosis de bolsa ileoanal puede no ser posible en algunos pacientes debido a limitaciones técnicas intraoperatorias.Evaluar los predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal y revisar el manejo.Revisión retrospectiva.Cleveland Clinic entre Enero de 2010 y mayo de 2018.Pacientes > 18 años que se sometieron a cirugía de bolsa ileoanal. Los pacientes con una creación exitosa de la bolsa según lo planeado se agruparon como "creación exitosa de anastomosis de bolsa ileoanal". Se revisaron los informes operativos de los pacientes que se sometieron a procedimientos alternativos para identificar los casos en que la bolsa se planificó preoperatoriamente pero se abandonó intraoperatoriamente (grupo de "anastomosis anal de bolsa ileoanal abandonada"). Se desarrollaron modelos de regresión logística multivariante para determinar los predictores del abandono intraoperatorio de la bolsa. También revisamos el manejo de pacientes que fallaron en la creación inicial de la bolsa.Predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal.A un total de 1438 pacientes se les ofreció una bolsa ileoanal; 21 (1.5%) experimentaron abandono de la bolsa debido a un alcance inadecuado (n = 17) y otras razones técnicas (n = 4). Estos pacientes se sometieron a procedimientos alternativos como ileostomía final o de asa con / sin proctectomía. El análisis de regresión logística multivariante indicó género masculino (OR, 6.021; IC 95%, 1.540-23.534), índice de masa corporal (OR, 1.217; IC 95%, 1.114-1.329) y procedimiento en 2 etapas (OR, 14.510; IC 95%, 4.123-51.064) como factores independientes asociados con el abandono intraoperatorio de la creación de la bolsa. Los procedimientos alternativos fueron la proctocolectomía total con ileostomía final (n = 14) y la colectomía abdominal total con ileostomía final sin proctectomía (n = 7). Finalmente, la creación de la bolsa se logró en 6/21 pacientes después de un intervalo medio de 8.8 (rango, 4.1-34.8) meses. Todos los pacientes tuvieron pérdida de peso intencional antes de la reintenta y colectomía abdominal total con ileostomía final sin proctectomía como procedimiento inicial.Naturaleza retrospectiva.El abandono de la bolsa ileoanal es raro y puede mitigarse mediante la colectomía abdominal total inicial y la pérdida de peso. Los pacientes masculinos y obesos tienen un mayor riesgo de fracaso. La evaluación intraoperatoria de la viabilidad de la bolsa ileoanal debe ocurrir antes de la disección rectal. Consulte Video Resumen en http://links.lww.com/DCR/B156. (Traducción-Dr. Yesenia Rojas-Kahlil).

    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  4. Gothai S, Muniandy K, Gnanaraj C, Ibrahim IAA, Shahzad N, Al-Ghamdi SS, et al.
    Biomed Pharmacother, 2018 Nov;107:1514-1522.
    PMID: 30257369 DOI: 10.1016/j.biopha.2018.08.112
    Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  5. Al-Jashamy K, Murad A, Zeehaida M, Rohaini M, Hasnan J
    Asian Pac J Cancer Prev, 2010;11(6):1765-8.
    PMID: 21338230
    Colorectal cancer (CRC) is the second most common cause of cancer mortality among men and women worldwide; the risk of its occurrence has been shown to be increased by chronic bacterial infections. A case control study was therefore carried out at Hospital Universiti Sains Malaysia (HUSM) to determine the incidence of colorectal cancer associated with S. bovis infection. A total of 166 stool specimens were collected from diseased patients and healthy individuals and S. bovis isolates were identified. Suspected colon tumor and cancer cases were diagnosed and confirmed. It was found that overall prevalence of S. bovis was 41 (24.7%) out of 166 cases studied. Some 41(48.6%) of these S. bovis isolates was found in patients with colonic polyps, adenocarcinomas, inflammatory bowel disease (IBD) and chronic gastrointestinal tract (GIT). It was also found that colorectal cancer incidence was 24.7%, adenocarinomas accounting for 51% with the highest incidence in the sigmoid part of the colon. Among the IBD and chronic GIT cases, ulcerative colitis featured in the majority of cases (41.4%). In conclusion, there is a high incidence of colorectal cancer associated with S. bovis.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications*
  6. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):30-36.
    PMID: 29024102 DOI: 10.1111/jgh.14018
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  7. 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.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  8. 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.

    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  9. 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.

    Matched MeSH terms: Inflammatory Bowel Diseases/complications
  10. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
    PMID: 29023903 DOI: 10.1111/jgh.14019
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
    Matched MeSH terms: Inflammatory Bowel Diseases/complications
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