Commentary on : Nunes T, Etchevers MJ, Garcia-Sanchez V. Impact of smoking cessation on the clini... more Commentary on : Nunes T, Etchevers MJ, Garcia-Sanchez V. Impact of smoking cessation on the clinical course of Crohn's disease under current therapeutic algorithms: a multicentre prospective study. Am J Gastroenterol 2016;111:411–19[OpenUrl][1][CrossRef][2][PubMed][3]. Smoking is the most well-studied environmental risk factor of inflammatory bowel diseases (IBDs). Ulcerative colitis is less prevalent in smokers and the converse is true for Crohn's disease (CD). Smoking has a detrimental effect on the course of CD including worse disease course, increased need for surgery, more frequent need for maintenance medications and higher need for biological agents.1–3 Smokers were found to have a significantly decreased survival free of stricturing disease or perianal complications, and had a higher rate of thiopurine therapy requirement.4 The benefit of smoking cessation on CD was … [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BGastroenterol%26rft.volume%253D111%26rft.spage%253D411%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fajg.2015.401%26rft_id%253Dinfo%253Apmid%252F26856753%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1038/ajg.2015.401&link_type=DOI [3]: /lookup/external-ref?access_num=26856753&link_type=MED&atom=%2Febmed%2F21%2F4%2F153.atom
Staff Specialist gastroenterologist, Director of Endoscopy and Head of the Inflammatory Bowel Dis... more Staff Specialist gastroenterologist, Director of Endoscopy and Head of the Inflammatory Bowel Disease Service at Concord Hospital, Clinical Professor of Medicine at University of Sydney and UNSW, and founding director of IBD Sydney, Australia. He has an international reputation for the management of inflammatory bowel diseases and for clinical research. Prof Leong has made a substantial contribution to research with over 120 high quality scientific publications. Amongst these are senior authorship of national and international consensus guidelines in both Australia and in Asia. His service includes executive positions in the Research Committee of the Gastroenterological Society of Australia, section editor of the Journal of Gastroenterology and Hepatology, and editorial board of the American Journal of Gastroenterology. He is an executive member of a number of government bodies including the Agency for Clinical Innovation of NSW Health nominated for expertise in IBD and the Cancer C...
Background Treatment persistence (duration of medication use) provides real-world evidence on the... more Background Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from the national population-based registry with no hierarchical prescribing order. We hypothesized immunotherapy co-therapy would increase persistence through decreased immunogenicity. Methods A randomly selected ten percent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005-June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Results 2499 patients were included consisting of 3713 lines of therapy (2864 CD, 849 UC) which equated to 7470 person-years of follow-up. In CD, UST had the highest overall persistence rate (median persistence rate >74.6% whe...
Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn’s disease (CD).... more Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn’s disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31–2.33) per 1000 CD patients. Only 11% (CI: 0.04–0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18–0.41), and 33% (CI: 0.26–0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.
ABSTRACT Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs durin... more ABSTRACT Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD. Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation. Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.
Inflammatory bowel disease (IBD) frequently affects women of childbearing age and can have implic... more Inflammatory bowel disease (IBD) frequently affects women of childbearing age and can have implications in pregnancy. Most women with IBD have comparable fertility with women in the general population. Fertility is reduced in women with active disease or previous ileal-pouch–anal anastomosis (IPAA) surgery and is temporarily reduced in men taking sulfasalazine. Women with IBD have an increased risk of preterm delivery, low birth weight, small-for-gestational-age infants and Cesarean section (CS) delivery, however, no increased risk of congenital abnormalities. These adverse outcomes are particularly prevalent for women with active IBD compared with those with quiescent disease. Conception should occur during disease remission to optimize maternal and fetal outcomes and reduce the risk of disease exacerbations during pregnancy. Pre-conception counseling is therefore pertinent to provide patient education, medication review for risk of teratogenicity and objective disease assessment. ...
IntroductionCrohn’s disease and ulcerative colitis are common chronic idiopathic inflammatory bow... more IntroductionCrohn’s disease and ulcerative colitis are common chronic idiopathic inflammatory bowel diseases (IBD), which cause considerable morbidity. Although the precise mechanisms of disease remain unclear, evidence implicates a strong multidirectional interplay between diet, environmental factors, genetic determinants/immune perturbations and the gut microbiota. IBD can be brought into remission using a number of medications, which act by suppressing the immune response. However, none of the available medications address any of the underlying potential mechanisms. As we understand more about how the microbiota drives inflammation, much interest has focused on identifying microbial signals/triggers in the search for effective therapeutic targets. We describe the establishment of the Australian IBD Microbiota (AIM) Study, Australia’s first longitudinal IBD bioresource, which will identify and correlate longitudinal microbial and metagenomics signals to disease activity as evaluat...
3545 Background: There has been a rapid rise in colorectal cancer (CRC) incidence in recent decad... more 3545 Background: There has been a rapid rise in colorectal cancer (CRC) incidence in recent decades in many Asian countries. Age, gender, smoking, and family history are the significant risk factors of CRC. This study would like to develop an Asia-Pacific Colorectal Screening (APCS) score to identify subjects with high-risk for colorectal advanced neoplasia (AN) in Asia. Methods: A multicentre study was in 11 Asian cities. A total of 7,463 asymptomatic subjects underwent screening colonoscopy. The first 2,000 subjects were used as a derivation cohort. AN was defined as advanced adenoma and CRC. A multiple logistic regression was applied to the derivation cohort identifying significant risk factors for AN; odds ratios of significant risk factors were then utilized to develop APCS score ranging from 0-6, including age (0=40-49, 1=50-59, 2=60+), gender (0=female, 1=male), family history (0=absent, 1=present), smoking (0=no, 1=current or past), and Body Mass Index (BMI) (0= 23kg/m2). Three tiers...
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tra... more Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract with multifactorial etiology. Both dietary factors and the microbe have been found to be associated with the condition. The current study examined the effects of sodium fumarate, a neutralized product of the food additives fumaric acid and monosodium fumarate when in the intestinal environment, on the growth of to determine the effects of these food additives on IBD-associated bacterial species. Through culture methods and quantification, it was found that neutralized fumaric acid, neutralized monosodium fumarate, and sodium fumarate increased the growth of , with the greatest increase in growth at a concentration of 0.4%. Further examination of 50 strains on media with added sodium fumarate showed that greatest growth was also achieved at a concentration of 0.4%. At a concentration of 2% sodium fumarate, all strains examined displayed less growth in comparison with those cultured on ...
Over the years, the scientific community has explored myriads of theories in search of the etiolo... more Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestin...
Commentary on : Nunes T, Etchevers MJ, Garcia-Sanchez V. Impact of smoking cessation on the clini... more Commentary on : Nunes T, Etchevers MJ, Garcia-Sanchez V. Impact of smoking cessation on the clinical course of Crohn's disease under current therapeutic algorithms: a multicentre prospective study. Am J Gastroenterol 2016;111:411–19[OpenUrl][1][CrossRef][2][PubMed][3]. Smoking is the most well-studied environmental risk factor of inflammatory bowel diseases (IBDs). Ulcerative colitis is less prevalent in smokers and the converse is true for Crohn's disease (CD). Smoking has a detrimental effect on the course of CD including worse disease course, increased need for surgery, more frequent need for maintenance medications and higher need for biological agents.1–3 Smokers were found to have a significantly decreased survival free of stricturing disease or perianal complications, and had a higher rate of thiopurine therapy requirement.4 The benefit of smoking cessation on CD was … [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BGastroenterol%26rft.volume%253D111%26rft.spage%253D411%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fajg.2015.401%26rft_id%253Dinfo%253Apmid%252F26856753%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1038/ajg.2015.401&link_type=DOI [3]: /lookup/external-ref?access_num=26856753&link_type=MED&atom=%2Febmed%2F21%2F4%2F153.atom
Staff Specialist gastroenterologist, Director of Endoscopy and Head of the Inflammatory Bowel Dis... more Staff Specialist gastroenterologist, Director of Endoscopy and Head of the Inflammatory Bowel Disease Service at Concord Hospital, Clinical Professor of Medicine at University of Sydney and UNSW, and founding director of IBD Sydney, Australia. He has an international reputation for the management of inflammatory bowel diseases and for clinical research. Prof Leong has made a substantial contribution to research with over 120 high quality scientific publications. Amongst these are senior authorship of national and international consensus guidelines in both Australia and in Asia. His service includes executive positions in the Research Committee of the Gastroenterological Society of Australia, section editor of the Journal of Gastroenterology and Hepatology, and editorial board of the American Journal of Gastroenterology. He is an executive member of a number of government bodies including the Agency for Clinical Innovation of NSW Health nominated for expertise in IBD and the Cancer C...
Background Treatment persistence (duration of medication use) provides real-world evidence on the... more Background Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from the national population-based registry with no hierarchical prescribing order. We hypothesized immunotherapy co-therapy would increase persistence through decreased immunogenicity. Methods A randomly selected ten percent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005-June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Results 2499 patients were included consisting of 3713 lines of therapy (2864 CD, 849 UC) which equated to 7470 person-years of follow-up. In CD, UST had the highest overall persistence rate (median persistence rate >74.6% whe...
Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn’s disease (CD).... more Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn’s disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31–2.33) per 1000 CD patients. Only 11% (CI: 0.04–0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18–0.41), and 33% (CI: 0.26–0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.
ABSTRACT Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs durin... more ABSTRACT Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD. Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation. Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.
Inflammatory bowel disease (IBD) frequently affects women of childbearing age and can have implic... more Inflammatory bowel disease (IBD) frequently affects women of childbearing age and can have implications in pregnancy. Most women with IBD have comparable fertility with women in the general population. Fertility is reduced in women with active disease or previous ileal-pouch–anal anastomosis (IPAA) surgery and is temporarily reduced in men taking sulfasalazine. Women with IBD have an increased risk of preterm delivery, low birth weight, small-for-gestational-age infants and Cesarean section (CS) delivery, however, no increased risk of congenital abnormalities. These adverse outcomes are particularly prevalent for women with active IBD compared with those with quiescent disease. Conception should occur during disease remission to optimize maternal and fetal outcomes and reduce the risk of disease exacerbations during pregnancy. Pre-conception counseling is therefore pertinent to provide patient education, medication review for risk of teratogenicity and objective disease assessment. ...
IntroductionCrohn’s disease and ulcerative colitis are common chronic idiopathic inflammatory bow... more IntroductionCrohn’s disease and ulcerative colitis are common chronic idiopathic inflammatory bowel diseases (IBD), which cause considerable morbidity. Although the precise mechanisms of disease remain unclear, evidence implicates a strong multidirectional interplay between diet, environmental factors, genetic determinants/immune perturbations and the gut microbiota. IBD can be brought into remission using a number of medications, which act by suppressing the immune response. However, none of the available medications address any of the underlying potential mechanisms. As we understand more about how the microbiota drives inflammation, much interest has focused on identifying microbial signals/triggers in the search for effective therapeutic targets. We describe the establishment of the Australian IBD Microbiota (AIM) Study, Australia’s first longitudinal IBD bioresource, which will identify and correlate longitudinal microbial and metagenomics signals to disease activity as evaluat...
3545 Background: There has been a rapid rise in colorectal cancer (CRC) incidence in recent decad... more 3545 Background: There has been a rapid rise in colorectal cancer (CRC) incidence in recent decades in many Asian countries. Age, gender, smoking, and family history are the significant risk factors of CRC. This study would like to develop an Asia-Pacific Colorectal Screening (APCS) score to identify subjects with high-risk for colorectal advanced neoplasia (AN) in Asia. Methods: A multicentre study was in 11 Asian cities. A total of 7,463 asymptomatic subjects underwent screening colonoscopy. The first 2,000 subjects were used as a derivation cohort. AN was defined as advanced adenoma and CRC. A multiple logistic regression was applied to the derivation cohort identifying significant risk factors for AN; odds ratios of significant risk factors were then utilized to develop APCS score ranging from 0-6, including age (0=40-49, 1=50-59, 2=60+), gender (0=female, 1=male), family history (0=absent, 1=present), smoking (0=no, 1=current or past), and Body Mass Index (BMI) (0= 23kg/m2). Three tiers...
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tra... more Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract with multifactorial etiology. Both dietary factors and the microbe have been found to be associated with the condition. The current study examined the effects of sodium fumarate, a neutralized product of the food additives fumaric acid and monosodium fumarate when in the intestinal environment, on the growth of to determine the effects of these food additives on IBD-associated bacterial species. Through culture methods and quantification, it was found that neutralized fumaric acid, neutralized monosodium fumarate, and sodium fumarate increased the growth of , with the greatest increase in growth at a concentration of 0.4%. Further examination of 50 strains on media with added sodium fumarate showed that greatest growth was also achieved at a concentration of 0.4%. At a concentration of 2% sodium fumarate, all strains examined displayed less growth in comparison with those cultured on ...
Over the years, the scientific community has explored myriads of theories in search of the etiolo... more Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestin...
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