ADALIMUMAB VERSUS INFLIXIMAB IN LUMINAL PEDIATRIC CROHN'S DISEASE: COMPARABLE OUTCOMES IN A PROSPECTIVE MULTICENTER COHORT STUDY.

BACKGROUND: This study compared real-world effectiveness between adalimumab (ADA) and infliximab (IFX) in children with Crohn's disease (CD). METHODS: Children enrolled into the prospective Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN) National Inception Cohort between 2014 and 2020 who commenced ADA or IFX as first anti-tumor necrosis factor (antiTNF) agent for luminal CD were included. Multivariate logistic regression modelled the propensity of commencing ADA; propensity score matching was used to match IFX-treated children to ADA-treated children. The primary outcome at one year was steroid-free clinical remission (SFCR). Secondary outcomes at one year were I) combined SFCR and c-reactive protein (CRP) remission; II) treatment intensification; and III) antiTNF durability. Odds ratios (aOR) and hazard ratio (aHR) adjusted for concomitant immunomodulator use with 95% confidence interval (CI) are reported. RESULTS: In the propensity score matched cohort of 147 ADA-treated and 147 IFX-treated children, 92 (63%) ADA- and 87 (59%) IFX-treated children achieved SFCR at one year (aOR: 1.4, 95% CI 0.9-2.4); 75 of 140 (54%) ADA- and 85 of 144 (59%) IFX-treated children achieved combined SFCR and CRP remission (aOR: 1.0, 95% CI 0.6-1.6). ADA-treated children less frequently underwent treatment intensification (21 [14%]) compared to IFX-treated children (69 [47%]) (P<0.0001). Discontinuation of antiTNF occurred in 18 (12%) ADA-treated and 15 (10%) IFX-treated children (aHR: 1.2, 95% CI 0.6-2.2). CONCLUSION: Children with Crohn's disease achieved favourable outcomes at one year with either ADA or IFX as first antiTNF agents. Those receiving IFX did not have significantly superior outcomes compared to clinically similar children receiving ADA.

Transition Readiness in Youth with Inflammatory Bowel Disease.

OBJECTIVES: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care. STUDY DESIGN: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19 years old prospectively recruited from 8 Canadian IBD centers using the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. Secondary aims included (1) screening for depression and anxiety using the 8-item Personal Health Questionnaire Depression Scale and The Screen for Child Anxiety Related Emotional Disorders questionnaires, respectively; (2) evaluating the association between depression and anxiety with readiness and disease activity; and (3) subjectively evaluating AYA readiness based on physician and parent assessments. RESULTS: In total, 186 participants (139 adolescent, 47 young adult) were enrolled, mean age 17.4 years (SD, 0.87). ON TRAC scores determined that 26.6% of AYAs at pediatric and 40.4% at adult centers reached the threshold of readiness. On multivariable linear regression analysis age was positively (P = .001) and disease remission negatively (P = .03) associated with ON TRAC scores. No statistically significant differences were determined across centers. A significant percentage of AYAs reported moderate-to-severe depression (21.7%) and generalized anxiety (36%); however, neither were significantly associated with ON TRAC scores. Notably, physician and parental assessment of AYA readiness correlated poorly with ON TRAC scores (⍴ = 0.11, ⍴ = 0.24, respectively). CONCLUSIONS: Assessment of transition readiness in AYAs with IBD highlighted that a large proportion do not have adequate knowledge or behavior skills needed for transition to adult care. This study infers that readiness assessment tools are essential during transition to identify deficits in knowledge and behavior skills that could be specifically targeted by the youth, caregivers, and multidisciplinary team.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 1: Live Vaccines.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on live vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Three good practice statements included reviewing a patient's vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient. CONCLUSIONS: Maintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.

Indirect and Out-of-Pocket Disease-associated Costs in Pediatric Inflammatory Bowel Disease: A Cross-sectional Analysis.

OBJECTIVES: Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada. METHODS: In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3-9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression. RESULTS: Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809-$12,676), with $5721 (IQR $1366-$11,545) for Crohn's disease (CD) and $7007 (IQR $2428-$14,057) for ulcerative colitis (UC) ( P = 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC ( P = 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55; P < 0.0001; 95% confidence interval: 1.99-10.40). CONCLUSIONS: Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.

Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.

OBJECTIVE: The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). METHODS: A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. RESULTS: Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. CONCLUSIONS: Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease.

BACKGROUND & AIMS: We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS: We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS: The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS: Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.

Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends. METHODS: MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time. RESULTS: Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades. DISCUSSION: Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.

Discontinuation of Immunosuppressive Medications in Children With Inflammatory Bowel Disease on Combination Therapy.

We determined the frequency and factors associated with the first clinical relapse after immunomodulator (IM) withdrawal in a cohort of children with inflammatory bowel disease on combination therapy. A total of 105 patients (89 with Crohn disease [CD]) in clinical remission were included (91 [86.7%] were on infliximab, 53 [50.5%] with methotrexate, and 52 on azathioprine). The median duration of combination therapy was 2.1 years (interquartile range [IQR] 1.3-2.8). Only 11 (10.5%) patients experienced a clinical relapse over a median duration of follow-up of 12.0 months (IQR 5.0-19.0) after IM discontinuation. The median baseline pediatric CD activity index in those with CD who relapsed after IM discontinuation was 47.5 (IQR: 35.0-55.0) versus those who did not relapse (median 35.0, IQR: 20.0-52.5; P = 0.04). In the patients who did not relapse, the median IFX trough level at IM discontinuation was 6.2 and 3.8 µg/mL in those who relapsed.

Viral and bacterial community responses to stimulated Fe(III)-bioreduction during simulated subsurface bioremediation.

The delivery of fermentable substrate(s) to subsurface environments stimulates Fe(III)-bioreduction and achieves detoxification of organic/inorganic contaminants. Although, much research has been conducted on the microbiology of such engineered systems at lab and field scales, little attention has been given to the phage-host interactions and virus community dynamics in these environments. The objective was to determine the responses of soil bacterial communities and viral assemblages to stimulated anaerobic Fe(III)-bioreduction following electron donor (e.g. acetate) addition. Microbial communities, including viral assemblages, were investigated after 60 days of Fe(III)-bioreduction in laboratory-scale columns continuously fed with acetate-amended artificial groundwater. Viral abundances were greatest in the influent section and decreased along the flow path. Acetate availability was important in influencing bacterial diversity, microbial interactions and viral abundance and community composition. The impact of acetate addition was most evident in the influent section of the columns. The increased relative abundance of Fe(III)-reducing bacteria coincided with an increase in viral abundance in areas of the columns exhibiting the most Fe(III) reduction. The genetic composition of viruses in these column sections also differed from the control column and distal sections of acetate-treated columns suggesting viral communities responded to biostimulated Fe(III)-bioreduction.

Clinical disease activity and endoscopic severity correlate poorly in children newly diagnosed with Crohn's disease.

BACKGROUND AND AIMS: Treatment goals in Crohn's disease (CD) have evolved to target mucosal healing. There is now a drive to determine if noninvasive measures can adequately identify the attainment and persistence of this goal. Currently, data describing the relationship between clinical indices and endoscopic appearance in pediatric CD are sparse. Our aim was to compare endoscopic severity with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) in children with newly diagnosed CD. METHODS: All children aged ≤17 years newly diagnosed with CD enrolled in an inception cohort at sites of the Canadian Children Inflammatory Bowel Disease Network were eligible. Clinical disease activity at presentation was evaluated by the wPCDAI and conventional biochemical parameters. Severity of disease at ileocolonoscopy was assessed by the simple endoscopic score for CD (SES-CD), with segmental subscores noted. We evaluated the association of SES-CD and disease activity markers using the Pearson test of correlation, the Spearman rank coefficient, and linear regression models. RESULTS: Two hundred eighty patients from 11 centers were included in the analysis. The median wPCDAI score was 60 (interquartile range, 40-80; 53% severe). Median SES-CD was 16 (interquartile range 10-22; 51% severe). The wPCDAI correlated weakly with SES-CD (r = .39, P < .001). Examination of the individual components that contribute to the wPCDAI demonstrated weak correlation with the SES-CD for all items apart from stooling (moderate correlation, r = .50, P < .001). Routine blood tests did not correlate well with the SES-CD. In regression models, variation in clinical symptoms accounted for most of the variation in both the wPCDAI and SES-CD, with no additional benefit from routine blood tests. CONCLUSIONS: In children with newly diagnosed CD, wPCDAI correlates poorly with endoscopic disease activity. As treatment paradigms evolve to target mucosal healing, clinical markers should not be used in isolation to determine disease activity.

The Simple Pediatric Activity Ultrasound Score (SPAUSS) for the Accurate Detection of Pediatric Inflammatory Bowel Disease.

OBJECTIVE: The aim of the study was to identify the most significant ultrasound (US) parameters that predict inflammatory activity and develop a simple US activity score. METHODS: Patients were identified through retrospective evaluation of an established database of children with inflammatory bowel disease (IBD). Patients with endoscopy and US within 60 days were included (N = 75). US parameters evaluated included: bowel wall thickness (BWT), mesenteric inflammatory fat, lymphadenopathy, and hyperemia. The weighted kappa statistic was calculated to assess agreement between sonographic and endoscopically identified disease location. Using a proportional odds model and ordinal logistic regression, statistically significant (P < 0.05) parameters were used to generate a score. Variables were weighted to classify individuals into severity classes. Receiver operating characteristic curves were plotted to demonstrate the score's discriminative and predictive capacity. RESULTS: There was substantial agreement between US and endoscopy for all disease locations (weighted kappa = 0.85) and substantial agreement for ileocolonic disease (weighted kappa = 0.96). Two sonographic parameters were identified as contributing significantly to disease activity: BWT and mesenteric inflammatory fat (P < 0.05). A predictive score was developed incorporating BWT, hyperemia and inflammatory fat, and receiver operating characteristic curve curves demonstrated good predictive capacity to distinguish between the absence of disease (normal) and active disease with an area under the curve of 82.1%. CONCLUSIONS: The most important sonographic parameters for predicting disease activity were BWT and mesenteric inflammatory fat. When combined with hyperemia into a simple score, there was accurate detection of inflammatory activity in children with inflammatory bowel disease. This score may facilitate noninvasive, bedside detection of inflammation, and standardize the use of US in children.

Long-term Outcomes of Infliximab Use for Pediatric Crohn Disease: A Canadian Multicenter Clinical Practice Experience.

BACKGROUND: Data on long-term real-world outcomes of infliximab in pediatric Crohn disease are limited. AIM: The aim of the study was to evaluate infliximab optimization and durability in children with Crohn disease. METHODS: We performed a retrospective review of children with Crohn disease who started infliximab from January 2008 to December 2012 in 4 Canadian tertiary care centers. A priori factors associated with optimization and discontinuation from loss of response were evaluated using logistic regression and Cox proportional hazards model, respectively. RESULTS: One hundred eighty children (54.4% boys) started infliximab; all completed induction. Median age at infliximab start was 14.3 years (Q1, Q3: 12.8, 15.9 years) and median time from diagnosis to infliximab start was 1.5 years (Q1, Q3: 0.6, 3.5 years). At last follow-up, 87.1% were maintained on infliximab (median duration follow-up 85.9 weeks [Q1, Q3: 43.8, 138.8 weeks]). Infliximab optimization occurred in 57.3% (dose escalation 15.2%, interval shortening 3.9%, both 38.2%), primarily due to loss of response. Younger age at diagnosis (<10 years old) and nonstricturing, nonpenetrating behavior were associated with optimization (odds ratio 6.5, 95% confidence interval [CI] 2.0-21.1 and odds ratio 2.1, 95% CI 1.0-4.2, respectively). The 1- and 2-year durability of infliximab (percentage in follow-up who were continuing on infliximab) were 95.5% (95% CI 90.4-98.3) and 91.0% (95% CI 82.4-96.3), respectively. Annual discontinuation due to loss of response occurred at 3.2% per year (95% CI 1.1-5.2). CONCLUSIONS: Children with Crohn disease maintain a durable response to infliximab. Optimization occurs frequently and allows for continued use. Younger age at diagnosis and nonstricturing, nonpenetrating behavior are associated with increased need for infliximab optimization.

Corrigendum: Rural and Urban Residence During Early Life Is Associated with a Lower Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study.

This corrects the article DOI: 10.1038/ajg.2017.208.

Rural and Urban Residence During Early Life is Associated with Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study

OBJECTIVES: To determine the association between inflammatory bowel disease (IBD) and rural/urban household at the time of diagnosis, or within the first 5 years (y) of life. METHODS: Population-based cohorts of residents of four Canadian provinces were created using health administrative data. Rural/urban status was derived from postal codes based on population density and distance to metropolitan areas. Validated algorithms identified all incident IBD cases from administrative data (Alberta: 1999-2008, Manitoba and Ontario: 1999-2010, and Nova Scotia: 2000-2008). We determined sex-standardized incidence (per 100,000 patient-years) and incident rate ratios (IRR) using Poisson regression. A birth cohort was created of children in whom full administrative data were available from birth (Alberta 1996-2010, Manitoba 1988-2010, and Ontario 1991-2010). IRR was calculated for residents who lived continuously in rural/urban households during each of the first 5 years of life. RESULTS: There were 6,662 rural residents and 38,905 urban residents with IBD. Incidence of IBD per 100,000 was 33.16 (95% CI 27.24-39.08) in urban residents, and 30.72 (95% CI 23.81-37.64) in rural residents (IRR 0.90, 95% CI 0.81-0.99). The protective association was strongest in children <10 years (IRR 0.58, 95% CI 0.43-0.73) and 10-17.9 years (IRR 0.72, 95% CI 0.64-0.81). In the birth cohort, comprising 331 rural and 2,302 urban residents, rurality in the first 1-5 years of life was associated with lower risk of IBD (IRR 0.75-0.78). CONCLUSIONS: People living in rural households had lower risk of developing IBD. This association is strongest in young children and adolescents, and in children exposed to the rural environment early in life.

The persistence of human DNA in soil following surface decomposition.

Though recent decades have seen a marked increase in research concerning the impact of human decomposition on the grave soil environment, the fate of human DNA in grave soil has been relatively understudied. With the purpose of supplementing the growing body of literature in forensic soil taphonomy, this study assessed the relative persistence of human DNA in soil over the course of decomposition. Endpoint PCR was used to assess the presence or absence of human nuclear and mitochondrial DNA, while qPCR was used to evaluate the quantity of human DNA recovered from the soil beneath four cadavers at the University of Tennessee's Anthropology Research Facility (ARF). Human nuclear DNA from the soil was largely unrecoverable, while human mitochondrial DNA was detectable in the soil throughout all decomposition stages. Mitochondrial DNA copy abundances were not significantly different between decomposition stages and were not significantly correlated to soil edaphic parameters tested. There was, however, a significant positive correlation between mitochondrial DNA copy abundances and the human associated bacteria, Bacteroides, as estimated by 16S rRNA gene abundances. These results show that human mitochondrial DNA can persist in grave soil and be consistently detected throughout decomposition.

Conservative Management of Downhill Esophageal Varices Secondary to Central Line-related Thrombosis After Hematopoietic Stem Cell Transplant.

Occlusive central line-related complications are not infrequent in children undergoing cancer therapy, but are generally not associated with life-threatening complications. Thrombosis of the superior vena cava (SVC) is rarely described in such patients, and downhill esophageal varices have been described in children and adults as a complication of altered SVC blood flow. The management of patients with SVC thrombosis and associated varices is complicated by the need to treat the thrombus weighed against bleeding risk. We present a 14-year-old adolescent with a history of acute leukemia and central line-related complications, including SVC thrombosis with subsequent formation of downhill esophageal varices. Conservative management consisting of anticoagulation alone resulted in resolution of the varices with no bleeding complications.

Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.

BACKGROUND & AIMS: The inflammatory bowel diseases (IBDs) are chronic diseases that often require surgery. However, the risk of requirement of surgery over time has not been well characterized. We performed a systematic review and meta-analysis to establish the cumulative risk of surgery among patients with IBD and evaluated how this risk has changed over time. METHODS: We searched Medline, EMBASE, PubMed, and conference proceedings (2009-2012) on May 8, 2013, for terms related to IBD and intestinal surgery. Two reviewers screened 8338 unique citations to identify 486 for full-text review. The analysis included population-based studies published as articles (n = 26) and abstracts (n = 4) that reported risks of surgery at 1, 5, or 10 years after a diagnosis of Crohn's disease and/or ulcerative colitis. The trend in risk of surgery over time was analyzed by meta-regression using mixed-effect models. RESULTS: Based on all population-based studies, the risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease was 16.3% (95% confidence interval [CI], 11.4%-23.2%), 33.3% (95% CI, 26.3%-42.1%), and 46.6% (95% CI, 37.7%-57.7%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of ulcerative colitis was 4.9% (95% CI, 3.8%-6.3%), 11.6% (95% CI, 9.3%-14.4%), and 15.6% (95% CI, 12.5%-19.6%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease and 1 and 10 years after diagnosis of ulcerative colitis has decreased significantly over the past 6 decades (P < .05). CONCLUSIONS: Based on systematic review and meta-analysis of population-based studies, the risk of intestinal surgery among patients with IBD has decreased over the past 6 decades.

Cumulative incidence of second intestinal resection in Crohn's disease: a systematic review and meta-analysis of population-based studies.

OBJECTIVES: Approximately 50% of Crohn's disease patients undergo an intestinal resection within 10 years of diagnosis. The risk of second surgery in Crohn's disease and the influence of time are not well characterized. We performed a systematic review and meta-analysis to establish the risk of second abdominal surgery in patients with Crohn's disease among patients who had a previous surgery. METHODS: We searched Medline, EMBASE, PubMed (March 2014), and conference proceedings for terms related to Crohn's disease and intestinal surgery. We included population-based articles (n=11) and an abstract (n=1) reporting surgical risk for the overall study period and for 5 and 10 years after the first surgery for Crohn's disease. We stratified studies by year (start year before vs. after 1980) to explore the role of time. RESULTS: For all population-based studies, the overall risk of second surgery was 28.7% (95% confidence interval (CI): 22.6-36.6%). The 5-year risk of second surgery was 24.2% (95% CI: 22.3-26.4%). The 10-year risk of second surgery was 35.0% (95% CI: 31.8-38.6%). A significant difference in the 10-year risk of second surgery was observed over time such that studies conducted after 1980 had a lower risk of second surgery (33.2%; 95% CI: 31.2-35.4%) compared with those that started before 1980 (44.6%; 95% CI: 37.7-52.7%). CONCLUSIONS: Approximately one-quarter of Crohn's disease patients who have a first surgery also have a second, and the majority of these surgeries occur within 5 years of the first surgery. The 10-year risk of second surgery is significantly decreasing over time.

Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study.

AIM: To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation. METHODS: Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI <10, no steroids ≥4 weeks]. RESULTS: Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively). CONCLUSION: The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.