Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease:a multicenter international study

Background and aims Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aim to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPTIC-IBD. Methods We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, classifications of colonic lesions, utilizing still images and videos. We invited gastroenterologists from Canada, Italy, and the UK, with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions following training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. Results One hundred seventeen participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (p 0.002) following training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between pre- and post-course (

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Stereotactic Injection of DTI-015 into Recurrent Malignant Gliomas: Phase I/II Trial

DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the intratumoral treatment of gliomas. The ethanol solvent vehicle facilitates a rapid and thorough saturation of the tumor with the dissolved anticancer agent BCNU. We conducted a phase I/II dose escalation study of DTI-015 in 40 heavily pretreated patients with inoperable recurrent malignant glioma. The study goals were to establish a maximally tolerated dose (MTD) for DTI-015 and assess its safety and activity. Patients received stereotactic intratumoral injection of DTI-015 under magnetic resonance imaging guidance. Dose escalation was performed in two phases. First, DTI-015 volume was escalated at a set BCNU concentration of 12.5 mg/ml; second, BCNU mg dose was escalated by increasing BCNU concentration to 30, 45, 60, and 75 mg/ml. A MTD of 5 ml and 240 mg was established. Twenty-five of 28 DTI-015 treatments (89%) using ≤MTD were administered safely without producing high-grade drug-related adverse events. Median survival for GBM patients administered DTI-015 at ≤MTD was 55 weeks. Magnetic resonance imaging demonstrated stable disease in 72% of evaluable patients with a median of 10.5 weeks. The results suggest that DTI-015 administered at ≤MTD is well tolerated and active in patients with inoperable recurrent GBM

Small molecule oral targeted therapies in ulcerative colitis.

The incidence and prevalence of ulcerative colitis are increasing globally. Although the exact cause and pathogenesis of this disease is unclear, research has led to a better understanding of the condition and to identification of new targets for therapy, which in turn has encouraged the development of new therapies. As well as biologic therapies, which have changed the way inflammatory bowel disease is managed, small molecules have been developed for the treatment of ulcerative colitis. These small molecule treatments are orally administered and are likely to bring a substantial shift in the way this chronic disease is treated. Oral therapies offer many advantages over infusion therapies, such as ease of use, increased acceptability by patients, and reduction of cost. This Review focuses not only on oral therapies that have been approved for use in ulcerative colitis, but also on those that are in development, providing a comprehensive overview for clinicians of available oral therapies and drugs that are likely to become available. We have also reviewed drugs that have shown promise in preclinical studies and could be effective future therapies

Clinical outcomes, predictors of prognosis and health economics consequences in IBD patients after discontinuation of the first biological therapy.

Background In real-world clinical practice, biologics in inflammatory bowel diseases (IBD) may be discontinued for a variety of reasons, including discontinuation initiated by gastroenterologists. The aims of the study are to report outcomes after discontinuation and predictors of prognosis after a minimum follow-up of 24 months; outcomes of gastroenterologist-initiated discontinuation with resulting direct cost implications on the health system were also studied. Methods IBD patients who discontinued their first-use biologics between January 2013 and December 2016 were identified at our tertiary centre. Reasons for discontinuation and pre-defined adverse outcomes (AO) were recorded. Data were analysed using univariable and multivariable logistic regressions within a machine learning technique to predict AO. Gastroenterologist-initiated discontinuations were analysed separately, and Kaplan-Meier survival analysis performed; direct costs of AO due to discontinuation were assessed. Results A total of 147 patients discontinued biologics (M = 74; median age 39 years; Crohn's Disease = 110) with median follow-up of 40 months (range 24-60 months). In the total cohort, there were fewer AO among gastroenterologist-initiated discontinuations compared with patient-initiated; 54% (of the total group) had AO within 6 months. Among 59 gastroenterologist-initiated discontinuations, 23 (40%) had IBD-related AO within 6 months and 53 (90%) patients had AO by end of follow-up. Some 44 (75%) patients needed to restart biologics during follow-up, and direct costs due to AO and restart of biologics were high. Conclusions The proportion of patients who have AO following discontinuation of biologics is high; clinicians need to carefully consider predictors of poor prognosis and high relapse rates when discussing discontinuation. The direct costs of managing AO probably offset theoretical economic gains, especially in the era where cost of biologics is reducing. Biologics should probably be continued without interruptions in most patients who have achieved remission for the duration these remain effective and safe

Raman spectroscopy accurately differentiates mucosal healing from non-healing and biochemical changes following biological therapy in inflammatory bowel disease.

BACKGROUND Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH. METHODS Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification. RESULTS A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively. CONCLUSION We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD

Fecal Calprotectin Thresholds to Predict Endoscopic Remission Using Advanced Optical Enhancement Techniques and Histological Remission in IBD Patients.

BACKGROUND Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn's disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques. PATIENTS AND METHODS In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients. Receiver operating characteristic curves were created to evaluate the optimum cut-off of FC to predict ER evaluated by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified PICaSSO (Paddington International Virtual Chromoendoscopy Score) for UC patients and Simple Endoscopic Score (SES-CD) in CD patients; and HR was scored by the Robarts Histology Index (RHI) and Nancy Index for UC and modified Riley for CD. RESULTS In UC patients, the best thresholds of FC to identify ER calculated with MES, UCEIS, and modified PICaSSO were 112, 148, and 161 mcg/g with accuracy of 86.9% 86.8%, and 81.6%, respectively. The best value of FC to predict HR was 112 mcg/g and 172 mcg/g with accuracy of 84.2% and 81.6% for RHI and Nancy Index, respectively.In CD patients, the best cut-off of FC to predict ER was 96 mcg/g with accuracy of 82.9%. The HR was best predicted by an FC value of 225 mcg/g with accuracy of 75.6%. CONCLUSIONS The FC value threshold between 112 and 172 mcg/g could identify ER and HR in UC patients, whereas a value under 225 mcg/g should be considered for CD patients