Publications by authors named "Ray Boyapati"

21 Publications

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Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

Dig Liver Dis 2021 03 26;53(3):263-270. Epub 2020 Dec 26.

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences "L.Sacco" University of Milan, Italy.

Background: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19.

Objectives: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders.

Methods: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed.

Results: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17).

Conclusion: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
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http://dx.doi.org/10.1016/j.dld.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762705PMC
March 2021

Precision medicine in inflammatory bowel disease: concept, progress and challenges.

F1000Res 2020 28;9. Epub 2020 Jan 28.

Department of Gastroenterology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK.

Crohn's disease and ulcerative colitis are increasingly prevalent, relapsing and remitting inflammatory bowel diseases (IBDs) with variable disease courses and complications. Their aetiology remains unclear but current evidence shows an increasingly complex pathophysiology broadly centring on the genome, exposome, microbiome and immunome. Our increased understanding of disease pathogenesis is providing an ever-expanding arsenal of therapeutic options, but these can be expensive and patients can lose response or never respond to certain therapies. Therefore, there is now a growing need to personalise therapies on the basis of the underlying disease biology and a desire to shift our approach from "reactive" management driven by disease complications to "proactive" care with an aim to prevent disease sequelae. Precision medicine is the tailoring of medical treatment to the individual patient, encompassing a multitude of data-driven (and multi-omic) approaches to foster accurate clinical decision-making. In IBD, precision medicine would have significant benefits, enabling timely therapy that is both effective and appropriate for the individual. In this review, we summarise some of the key areas of progress towards precision medicine, including predicting disease susceptibility and its course, personalising therapies in IBD and monitoring response to therapy. We also highlight some of the challenges to be overcome in order to deliver this approach.
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http://dx.doi.org/10.12688/f1000research.20928.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993839PMC
October 2020

Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews.

Inflamm Bowel Dis 2019 02;25(3):472-478

Robarts Clinical Trials Inc. London, Ontario, Canada.

A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.
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http://dx.doi.org/10.1093/ibd/izy268DOI Listing
February 2019

Patients' perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey.

Scand J Gastroenterol 2018 Dec 18;53(12):1437-1442. Epub 2018 Nov 18.

a Department of Gastroenterology , Royal Bolton Hospital , Bolton , UK.

Introduction: Despite its success, there appears to be practical issues with Faecal Calprotectin (FC) testing in Inflammatory Bowel Diseases (IBD), including sample collection, delivery and processing delays. Patients' perception and barriers to FC testing are yet to be explored in clinical practice.

Method: A prospective patient survey was undertaken at IBD units in UK, Europe and Australia. A 9-point patient-based questionnaire was completed in clinic and included demographics, previous FC testing and FC sample difficulty rating score. Predictors of testing difficulty were derived using multivariable logistic regression analysis.

Results: A total of 585 patients with IBD completed the survey; 306 males with a median age of 43 years (IQR: 31-54). There were 446 patients (76%) who had prior FC testing experience. Of these, 37% (n = 165) rated FC testing difficult; 'sample collection' (n = 106; 67%) being the most common reason reported. Multivariable regression analysis identified age <49 years (odds ratio (OR): 2.5, CI:1.6-4.0), disease duration <35 months (OR 1.4, CI:0.9-2.1) and testing location (UK centre: OR 1.9, CI:1.2-3.1) as predictors of a difficult FC rating score.

Conclusions: A total of 37% of patients find FC testing challenging, in particular those aged <49 years, disease duration <35 months. Further studies understanding and addressing these practical issues may aid higher FC uptake in clinic.
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http://dx.doi.org/10.1080/00365521.2018.1527394DOI Listing
December 2018

Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.

Cochrane Database Syst Rev 2018 May 12;5:CD012540. Epub 2018 May 12.

Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia.

Background: Crohn's disease (CD) is a chronic, relapsing and remitting disease of the gastrointestinal tract that can cause significant morbidity and disability. Current treatment guidelines recommend early intervention with immunosuppressant or biological therapy in high-risk patients with a severe disease phenotype at presentation. The feasibility of therapeutic de-escalation once remission is achieved is a commonly encountered question in clinical practice, driven by patient and clinician concerns regarding safety, adverse events, cost and national regulations. Withdrawal of immunosuppressant and biologic drugs in patients with quiescent CD may limit adverse events and reduce healthcare costs. Alternatively, stopping these drug therapies may result in negative outcomes such as disease relapse, drug desensitization, bowel damage and need for surgery.

Objectives: To assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD.

Search Methods: We searched CENTRAL, MEDLINE, Embase and the Cochrane IBD Group Specialized Register from inception to 19 December 2017. We also searched the reference lists of potentially relevant manuscripts and conference proceedings to identify additional studies.

Selection Criteria: Randomized controlled trials (RCTs) and prospective cohort studies that followed patients for a minimum duration of six months after drug discontinuation were considered for inclusion. The patient population of interest was adults (> 18 years) with CD (as defined by conventional clinical, endoscopic or histologic criteria) who had achieved remission while receiving immunosuppressant or biologic drugs administered alone or in combination. Patients then discontinued the drug regimen following a period of maintenance therapy of at least six months. The comparison was usual care (i.e. continuation of the drug regimen).

Data Collection And Analysis: The primary outcome measure was the proportion of patients who relapsed following discontinuation of immunosuppressant or biologic drugs, administered alone or in combination. Secondary outcomes included: the proportion of patients who responded to the reintroduction of immunosuppressant or biologic drugs, given as monotherapy or combination therapy; the proportion of patients who required surgery following relapse; the proportion of patients who required hospitalization for CD following relapse; the proportion of patients who developed new CD-related complications (e.g. fistula, abscesses, strictures) following relapse; the proportion of patients with elevated biomarkers of inflammation (CRP, fecal calprotectin) in those who stop and those who continue therapy; the proportion of patients with anti-drug antibodies and low serum trough drug levels; time to relapse; and the proportion of patients with adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). Data were analyzed on an intention-to-treat basis where patients with missing outcome data were assumed to have relapsed. The overall quality of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria.

Main Results: A total of six RCTs (326 patients) evaluating therapeutic discontinuation in patients with quiescent CD were eligible for inclusion. In four RCTs azathioprine monotherapy was discontinued, and in two RCTs azathioprine was discontinued from a combination therapy regimen consisting of azathioprine with infliximab. No studies of biologic monotherapy withdrawal were eligible for inclusion. The majority of studies received unclear or low risk of bias ratings, with the exception of three open-label RCTs, which were rated as high risk of bias for blinding. Four RCTs (215 participants) compared discontinuation to continuation of azathioprine monotherapy, while two studies (125 participants) compared discontinuation of azathioprine from a combination regimen to continuation of combination therapy. Continuation of azathioprine monotherapy was shown to be superior to withdrawal for risk of clinical relapse. Thirty-two per cent (36/111) of azathioprine withdrawal participants relapsed compared to 14% (14/104) of participants who continued with azathioprine therapy (RR 0.42, 95% CI 0.24 to 0.72, GRADE low quality evidence). However, it is uncertain if there are any between-group differences in new CD-related complications (RR 0.34, 95% CI 0.06 to 2.08, GRADE low quality evidence), adverse events (RR 0.88, 95% CI 0.67 to 1.17, GRADE low quality evidence), serious adverse events (RR 3.29, 95% CI 0.35 to 30.80, GRADE low quality evidence) or withdrawal due to adverse events (RR 2.59, 95% CI 0.35 to 19.04, GRADE low quality evidence). Common adverse events included infections, mild leukopenia, abdominal symptoms, arthralgias, headache and elevated liver enzymes. No differences between azathioprine withdrawal from combination therapy versus continuation of combination therapy were observed for clinical relapse. Among patients who continued combination therapy with azathioprine and infliximab, 48% (27/56) had a clinical relapse compared to 49% (27/55) of patients discontinued azathioprine but remained on infliximab (RR 1.02, 95% CI 0.68 to 1.52, P = 0.32; GRADE low quality evidence). The effects on adverse events (RR 1.11, 95% CI 0.44 to 2.81, GRADE low quality of evidence) or serious adverse events are uncertain (RR 1.00, 95% CI 0.21 to 4.66; GRADE very low quality of evidence). Common adverse events in the combination therapy studies included infections, liver test elevations, arthralgias and infusion reactions.

Authors' Conclusions: The effects of withdrawal of immunosuppressant therapy in people with quiescent Crohn's disease are uncertain. Low quality evidence suggests that continuing azathioprine monotherapy may be superior to withdrawal for avoiding clinical relapse, while very low quality evidence suggests that there may be no difference in clinical relapse rates between discontinuing azathioprine from a combination therapy regimen, compared to continuing combination therapy. It is unclear whether withdrawal of azathioprine, initially administered alone or in combination, impacts on the development of CD-related complications, adverse events, serious adverse events or withdrawal due to adverse events. Further high-quality research is needed in this area, particularly double-blind RCTs in which biologic therapy or an immunosuppressant other than azathioprine is withdrawn.
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http://dx.doi.org/10.1002/14651858.CD012540.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494506PMC
May 2018

Mitochondrial DNA Is a Pro-Inflammatory Damage-Associated Molecular Pattern Released During Active IBD.

Inflamm Bowel Dis 2018 09;24(10):2113-2122

MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.

Background: Due to common evolutionary origins, mitochondrial DNA (mtDNA) shares many similarities with immunogenic bacterial DNA. MtDNA is recognized as a pro-inflammatory damage-associated molecular pattern (DAMP) with a pathogenic role in several inflammatory diseases. We hypothesised that mtDNA is released during active disease, serving as a key pro-inflammatory factor in inflammatory bowel disease (IBD).

Methods: Between 2014 and 2015, we collected plasma separated within 2 hours of sampling from 97 prospectively recruited IBD patients (67 ulcerative colitis [UC] and 30 Crohn's disease [CD]) and 40 non-IBD controls. We measured circulating mtDNA using quantitative polymerase chain reaction (amplifying mitochondria COXIII/ND2 genes) and also in mouse colitis induced by dextran sulfate-sodium (DSS). We used a mass spectometry approach to detect free plasma mitochondrial formylated peptides. Furthermore, we examined for mitochondrial damage using electron microscopy (EM) and TLR9 expression, the target for mtDNA, in human intestinal IBD mucosa.

Results: Plasma mtDNA levels were increased in UC and CD (both P < 0.0001) compared with non-IBD controls. These levels were significantly correlated to blood (C-reactive protein, albumin, white cell count), clinical and endoscopic markers of severity, and disease activity. In active UC, we identified 5 mitochondrial formylated peptides (the most abundant being fMMYALF with known chemoattractant function) in plasma. We observed mitochondrial damage in inflamed UC mucosa and significantly higher fecal MtDNA levels (vs non-IBD controls [P < 0.0001]), which supports gut mucosal mitochondrial DAMP release as the primary source. In parallel, plasma mtDNA levels increased during induction of acute DSS colitis and were associated with more severe colitis (P < 0.05). In active IBD, TLR9+ lamina propria inflammatory cells were significantly higher in UC and CD compared with controls (P < 0.05).

Conclusions: We present the first evidence to show that mtDNA is released during active IBD. MtDNA is a potential mechanistic biomarker, and our data point to mtDNA-TLR9 as a therapeutic target in IBD. 10.1093/ibd/izy095_videoizy095.video5776747659001.
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http://dx.doi.org/10.1093/ibd/izy095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301773PMC
September 2018

Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases.

F1000Res 2017 20;6:169. Epub 2017 Feb 20.

MRC Centre for Inflammation Research Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.

Mitochondrial DNA (mtDNA) has many similarities with bacterial DNA because of their shared common ancestry. Increasing evidence demonstrates mtDNA to be a potent danger signal that is recognised by the innate immune system and can directly modulate the inflammatory response. In humans, elevated circulating mtDNA is found in conditions with significant tissue injury such as trauma and sepsis and increasingly in chronic organ-specific and systemic illnesses such as steatohepatitis and systemic lupus erythematosus. In this review, we examine our current understanding of mtDNA-mediated inflammation and how the mechanisms regulating mitochondrial homeostasis and mtDNA release represent exciting and previously under-recognised important factors in many human inflammatory diseases, offering many new translational opportunities.
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http://dx.doi.org/10.12688/f1000research.10397.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321122PMC
February 2017

Can Thiopurines Prevent Formation of Antibodies Against Tumor Necrosis Factor Antagonists After Failure of These Therapies?

Clin Gastroenterol Hepatol 2017 01 5;15(1):76-78. Epub 2016 Oct 5.

Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.

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http://dx.doi.org/10.1016/j.cgh.2016.09.152DOI Listing
January 2017

Biomarkers in Search of Precision Medicine in IBD.

Am J Gastroenterol 2016 Dec 27;111(12):1682-1690. Epub 2016 Sep 27.

MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.

The completion of the human genome project in 2003 represented a major scientific landmark, ushering in a new era with hopes and expectations of fresh insights into disease mechanisms and treatments. In inflammatory bowel disease (IBD), many important discoveries soon followed, notably the identification of >200 genetic susceptibility loci and characterization of the gut microbiome. As "big data", driven by advances in technology, becomes increasingly available and affordable, individuals with IBD and clinicians alike yearn for tangible outcomes from the promise of "precision medicine"-precise diagnosis, monitoring, and treatment. Here, we provide a commentary on the prospects and challenges of precision medicine and biomarkers in IBD. We focus on the three key areas where precision IBD will have the most impact: (1) disease susceptibility, activity, and behavior; (2) prediction of drug response and adverse effects; and (3) identification of subphenotypic mechanisms to facilitate drug discovery and selection of new treatments in IBD.
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http://dx.doi.org/10.1038/ajg.2016.441DOI Listing
December 2016

Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases.

Am J Gastroenterol 2016 Dec 6;111(12):1796-1805. Epub 2016 Sep 6.

Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.

Objectives: There is an unmet need for novel blood-based biomarkers that offer timely and accurate diagnostic and prognostic testing in inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic utility of serum calprotectin (SC) in IBD.

Methods: A total of 171 patients (n=96 IBD, n=75 non-IBD) were prospectively recruited. A multi-biomarker model was derived using multivariable logistic regression analysis. Cox proportional hazards model was derived to assess the contribution of each variable to disease outcomes.

Results: SC correlated strongly with current biomarkers, including fecal calprotectin (FC) (n=50, ρ=0.50, P=1.6 × 10). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37 (95% confidence interval (CI): 2.82-34.68), P=4.00 × 10) compared with other markers (C-reactive protein (CRP): OR 8.52 (95% CI: 2.75-28.63), P=2.80 × 10); albumin: OR 6.12 (95% CI: 1.82-22.16), P=0.004). In a subset of 50 patients with paired SC and FC, the area under receiver operating characteristic discriminating IBD from controls was better for FC than for SC (0.99, (95% CI 0.87-1.00) and 0.87 (95% CI:0.78-0.97), respectively; P=0.01). At follow-up (median 342 days; interquartile range: 88-563), SC predicted treatment escalation and/or surgery in IBD (hazard ratio (HR) 2.7, 95% CI: 1.1-4.9), in particular Crohn's disease (CD) (HR 4.2, 95% CI 1.2-15.3). A model incorporating SC and either CRP or albumin has a positive likelihood ratio of 24.14 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of cases (95% CI: 43-79%) and 80% (95% CI: 31-94%) in CD if ≥2 blood marker criteria are met.

Conclusions: A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts.
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http://dx.doi.org/10.1038/ajg.2016.342DOI Listing
December 2016

Suspected acute hemolytic transfusion reaction mediated by anti-Di(a).

Immunohematology 2015 ;31(4):163-5

Austin Pathology, Austin Hospital, Heidelberg, Victoria, Australia.

Anti-Di(a) can mediate hemolytic disease of the fetus and newborn, but it is unclear if it can cause hemolytic transfusion reactions (HTRs). To date, there has only been one report of a possible immediate HTR attributed to anti-Di(a). Our case report details an immediate HTR due to anti-Di(a) in a patient with pre-existing liver failure. This reaction triggered multi-organ failure, and the patient subsequently died. This case also highlights the importance of considering HTRs even when routine antibody screening has been unremarkable, particularly when electronic crossmatch is used, because of the potential for an alloantibody against a low-prevalence antigen.
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August 2016

Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems.

Gastrointest Endosc 2016 Jun 26;83(6):1151-60. Epub 2015 Oct 26.

Department of Gastroenterology and Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia; Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.

Background And Aims: The American College of Gastroenterology recommends early risk stratification in patients presenting with upper GI bleeding (UGIB). The AIMS65 score is a risk stratification score previously validated to predict inpatient mortality. The aim of this study was to validate the AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB and to compare it with established pre- and postendoscopy risk scores.

Methods: ICD-10 (International Classification of Diseases, Tenth Revision) codes identified patients presenting with UGIB requiring endoscopy. All patients were risk stratified by using the AIMS65, Glasgow-Blatchford score (GBS), pre-endoscopy Rockall, and full Rockall scores. The primary outcome was inpatient mortality. Secondary outcomes were a composite endpoint of inpatient mortality, rebleeding, and endoscopic, radiologic, or surgical intervention; blood transfusion requirement; intensive care unit (ICU) admission; rebleeding; and hospital length of stay. The area under the receiver-operating characteristic curve (AUROC) was calculated for each score.

Results: Of the 424 study patients, 18 (4.2%) died and 69 (16%) achieved the composite endpoint. The AIMS65 score was superior to both the GBS (AUROC, 0.80 vs 0.76, P < .027) and the pre-endoscopy Rockall score (0.74, P = .001) and equivalent to the full Rockall score (0.78, P = .18) in predicting inpatient mortality. The AIMS65 score was superior to all other scores in predicting the need for ICU admission and length of hospital stay. AIMS65, GBS, and full Rockall scores were equivalent (AUROCs, 0.63 vs 0.62 vs 0.63, respectively) and superior to pre-endoscopy Rockall (AUROC, 0.55) in predicting the composite endpoint. GBS was superior to all other scores for predicting blood transfusion.

Conclusion: The AIMS65 score is a simple risk stratification score for UGIB with accuracy superior to that of GBS and pre-endoscopy Rockall scores in predicting in-hospital mortality and the need for ICU admission.
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http://dx.doi.org/10.1016/j.gie.2015.10.021DOI Listing
June 2016

Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease.

Gastroenterology 2015 Dec 14;149(7):1716-30. Epub 2015 Sep 14.

Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland.

Little is known about the optimal duration of therapy with an anti-tumor necrosis factor (TNF) agent and/or an immunomodulator for patients with inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (drug cessation or dose reduction) of anti-TNF agents and/or immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de-escalation [drug cessation or dose reduction] of immunomodulator monotherapy, 8 on immunomodulator de-escalation from combination therapy, and 43 on de-escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with Crohn's disease or ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after therapy was stopped). Most studies of patients with Crohn's disease who discontinued an immunomodulator after combination therapy found that rates of relapse did not differ from those of patients who continued taking the drug (55%-60% had disease relapse 24 months after they stopped taking the immunomodulator). The only study in patients with ulcerative colitis supported continued immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost.
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http://dx.doi.org/10.1053/j.gastro.2015.08.055DOI Listing
December 2015

Pathogenesis of Crohn's disease.

F1000Prime Rep 2015 2;7:44. Epub 2015 Apr 2.

Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh Edinburgh, EH16 4TJ UK ; Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital Edinburgh, EH4 2XU UK.

Significant progress in our understanding of Crohn's disease (CD), an archetypal common, complex disease, has now been achieved. Our ability to interrogate the deep complexities of the biological processes involved in maintaining gut mucosal homeostasis is a major over-riding factor underpinning this rapid progress. Key studies now offer many novel and expansive insights into the interacting roles of genetic susceptibility, immune function, and the gut microbiota in CD. Here, we provide overviews of these recent advances and new mechanistic themes, and address the challenges and prospects for translation from concept to clinic.
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http://dx.doi.org/10.12703/P7-44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447044PMC
June 2015

AIMS65: a promising upper gastrointestinal bleeding risk score but further validation required.

World J Gastroenterol 2014 Oct;20(39):14515-6

Ray Boyapati, Avik Majumdar, Marcus Robertson, Department of Gastroenterology and Liver Transplant, Austin Hospital, Heidelberg VIC 3084, Australia.

A novel upper gastrointestinal bleeding risk stratification score (AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivity in calculation. We comment on a recent study that has cast doubt on the applicability of AIMS65 in the peptic ulcer disease population. Although promising, further studies are required to evaluate the validity of AIMS65 in various populations.
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http://dx.doi.org/10.3748/wjg.v20.i39.14515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202383PMC
October 2014

One fifth of hospitalizations for peptic ulcer-related bleeding are potentially preventable.

World J Gastroenterol 2014 Aug;20(30):10504-11

Ray Boyapati, Sim Ye Ong, Bei Ye, Rhys Vaughan, Mayur Garg, Gastroenterology and Liver Transplant Unit, Austin Hospital, Melbourne, Victoria 3128, Australia.

Aim: To calculate the proportion of potentially preventable hospitalizations due to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED).

Methods: Retrospective cohort study using ICD-10 codes to identify all patients with upper gastrointestinal hemorrhage secondary to endoscopically proven PUD, EG or ED during the period from March 2007 to October 2010 in three major metropolitan hospitals in Melbourne, Australia. Patients were divided into "high risk" (those who would benefit from gastroprotection) and "not high risk" groups as defined by established guidelines. Mean Rockall score, transfusion requirement, length of stay, rebleeding rates, need for surgery and in-hospital mortality was compared between "high risk" and "not high risk" groups. Within the "high risk" group, those on gastroprotection and those with no gastroprotection were also compared.

Results: Five hundred and seven patients were included for analysis of which 174 were classified as high risk. Median values of complete Rockall Score (5 vs 4, P = 0.002) and length of stay (5 d vs 4 d, P = 0.04) were higher in the high risk group but in-hospital mortality was lower (0.6% vs 3.9%, P = 0.03). 130 out of the 174 patients in the high risk group were not taking recommended gastroprotective therapy prior to hospitalization. Past history of PUD (OR = 3.7, P = 0.006) and clopidogrel use (OR = 3.2, P = 0.007) significantly predicted prescription of gastroprotective therapy. Using proton pump inhibitor protection rates of 50%-85% from published studies, an estimation of 13% to 22% of the total number of the hospitalizations due to PUD or EG/ED related bleeding may have been preventable.

Conclusion: Up to one fifth of all hospitalizations for bleeding secondary to PUD or EG/ED are potentially preventable.
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http://dx.doi.org/10.3748/wjg.v20.i30.10504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130859PMC
August 2014

Acute liver injury secondary to sertraline.

BMJ Case Rep 2013 Sep 26;2013. Epub 2013 Sep 26.

Department of Gastroenterology and Hepatology, Monash Medical Centre, Monash Health, Melbourne, Australia.

Sertraline is widely prescribed to treat depression and anxiety disorders. However, hepatitis secondary to its use is a rare entity. We report the case of a 26-year-old woman in her 20th week of pregnancy presented with nausea, vomiting, malaise and dark urine. This occurred 6 months after sertraline 50 mg daily was started for the treatment of depression. Three weeks prior to her presentation, the dose of sertraline was increased to 100 mg daily. The patient's liver biochemical profile demonstrated increased transaminases. The biopsy of the liver showed lobular hepatitis, with a mild prominence of eosinophils, suggestive of a drug-induced or toxin-induced aetiology. Extensive biochemical work-up failed to show any other pathology to account for her hepatitis. Liver function tests normalised after cessation of sertraline, indicating a probable association between sertraline use and acute hepatocellular injury in our patient.
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http://dx.doi.org/10.1136/bcr-2013-201022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794285PMC
September 2013

Portal biliary ductopathy caused by cavernous transformation of the portal vein.

BMJ Case Rep 2013 Jan 31;2013. Epub 2013 Jan 31.

Department of Gastroenterology, Southern Health, Clayton, Victoria, Australia.

A 42-year-old woman presented with a 1-week history of epigastric pain and deranged liver function tests (LFTs) on a background of known portal vein thrombosis (PVT) with cavernous transformation. Imaging with ultrasound, CT and MR cholangiopancreatography demonstrated known PVT, with distortion of the common bile duct and a bulky head/proximal body of the pancreas, thought to be due to mass effect from cavernous transformation related to PVT. At endoscopic retrograde cholangiopancreatography, the common hepatic duct was noted to be smaller in diameter, without any filling defects or discrete strictures. Sphincterotomy and balloon trawl was performed, with subsequent improvement of the woman's LFTs and abdominal pain.
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http://dx.doi.org/10.1136/bcr-2012-008339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604330PMC
January 2013

An unusual presentation of herpes simplex virus encephalitis.

Case Rep Med 2012 6;2012:241710. Epub 2012 Sep 6.

Department of Medicine, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia.

We present a case of a 65-year-old man with an acute alteration in mental state that was initially diagnosed as a functional psychiatric condition. After extensive workup, herpes simplex virus type 1 (HSV-1) was detected in the patient's cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and he responded rapidly to treatment with acyclovir. The case illustrates the importance of actively excluding organic causes in such patients, the need to have a low threshold of suspicion for HSV encephalitis, and the central role of CSF PCR testing for the diagnosis of HSV encephalitis, even in the absence of CSF biochemical abnormalities.
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http://dx.doi.org/10.1155/2012/241710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443586PMC
September 2012

Young woman with recurrent vomiting associated with weight loss.

Gut 2013 Apr 21;62(4):592-3, 649. Epub 2012 Jun 21.

Gastroenterology and Liver Transplant Unit, Level 8, Harold Stokes Building, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia.

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http://dx.doi.org/10.1136/gutjnl-2012-302831DOI Listing
April 2013