A scoping review of educational programmes on artificial intelligence (AI) available to medical imaging staff.

INTRODUCTION: Medical imaging is arguably the most technologically advanced field in healthcare, encompassing a range of technologies which continually evolve as computing power and human knowledge expand. Artificial Intelligence (AI) is the next frontier which medical imaging is pioneering. The rapid development and implementation of AI has the potential to revolutionise healthcare, however, to do so, staff must be competent and confident in its application, hence AI readiness is an important precursor to AI adoption. Research to ascertain the best way to deliver this AI-enabled healthcare training is in its infancy. The aim of this scoping review is to compare existing studies which investigate and evaluate the efficacy of AI educational interventions for medical imaging staff. METHODS: Following the creation of a search strategy and keyword searches, screening was conducted to determine study eligibility. This consisted of a title and abstract scan, then subsequently a full-text review. Articles were included if they were empirical studies wherein an educational intervention on AI for medical imaging staff was created, delivered, and evaluated. RESULTS: Of the initial 1309 records returned, n = 5 (∼0.4 %) of studies met the eligibility criteria of the review. The curricula and delivery in each of the five studies shared similar aims and a 'flipped classroom' delivery was the most utilised method. However, the depth of content covered in the curricula of each varied and measured outcomes differed greatly. CONCLUSION: The findings of this review will provide insights into the evaluation of existing AI educational interventions, which will be valuable when planning AI education for healthcare staff. IMPLICATIONS FOR PRACTICE: This review highlights the need for standardised and comprehensive AI training programs for imaging staff.

The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis.

INTRODUCTION: Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis. METHODS: In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32-224), EQ-5D™ and EORTC-QLQ-C30-QL scores. RESULTS: A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P < 0·001), 0·80 (P = 0·003) and 61·0 (P < 0·001) respectively. After a median of 3·7 (range 2·3-5·2) years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time. CONCLUSION: Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.

ANTECEDENTES: La apendicectomía puede reducir las recaídas y la necesidad de medicación en pacientes con colitis ulcerosa (ulcerative colitis, UC), sin embargo, faltan datos a largo plazo obtenidos de forma prospectiva. El objetivo de este estudio fue analizar el efecto de la apendicectomía en pacientes con UC refractarios al tratamiento. MÉTODOS: En esta serie prospectiva de cohortes multicéntrica, a todos los pacientes consecutivos con UC refractaria remitidos para proctocolectomía entre noviembre de 2012 y junio de 2015 se les recomendó en su lugar someterse a una apendicectomía laparoscópica. El criterio de valoración principal fue la respuesta clínica (disminución de ≥ 3 puntos del sistema de puntuación parcial de Mayo que varía de 0 a 9) a los 12 meses y en el seguimiento a largo plazo. Los criterios de valoración secundarios incluyeron la remisión endoscópica (puntuación endoscópica de Mayo ≤ 1), fracaso (colectomía o inicio de medicación experimental) y cambios en el IBDQ (rango 32-224), EQ-5D y EORTC-QLQ-C30-QL. RESULTADOS: En total, 28 pacientes (13 mujeres, mediana de edad 40,5) se sometieron a una apendicectomía. El IBDQ de referencia promedio fue de 127,0; el EQ-5D 0,65 y el EORTC-QLQ-C30-QL 41,1. A los 12 meses, 13 pacientes presentaban una respuesta clínica, cinco estaban en remisión endoscópica y nueve precisaron colectomía (n = 6) o un nuevo tratamiento médico experimental (n = 3). El IBDQ, EQ-5D y EORTC-QLQ-C30-QL mejoraron a 167,1 (P < 0,001); 0,80 (P = 0,003) y 61,0 (P < 0,001) respectivamente. Después de una mediana de 3,7 años (rango 2,3-5,2), otros cuatro pacientes requirieron una colectomía (n = 2) o un nuevo tratamiento médico experimental (n = 2). Trece pacientes presentaron respuesta clínica y siete se encontraban en remisión endoscópica. La mejora del IBDQ, el EQ-5D y el EORTC-QLQ-C30-QL se mantuvo estable a lo largo del tiempo. CONCLUSIÓN: La apendicectomía consiguió una respuesta clínica en casi la mitad de los pacientes con UC refractaria. La apendicectomía electiva debería ser considerada antes que la proctocolectomía en pacientes con UC refractaria al tratamiento.

Appendectomy for Therapy-Refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation: Short-Term Results of the PASSION Study.

BACKGROUND AND AIMS: The objective of this study was to examine the modulating effect of an appendectomy on the disease course of therapy-refractory ulcerative colitis [UC] patients, and to analyse appendiceal pathological characteristics predictive of pathological response. METHODS: Patients with therapy-refractory UC, and referred for proctocolectomy, were invited to undergo laparoscopic appendectomy first. The primary end points were clinical response after 3 and 12 months. Secondary end points were endoscopic remission, failure, and pathologic response. Appendiceal specimens, and pre- and post-operative biopsies were histologically graded according to the validated Geboes score. RESULTS: Thirty patients [53% male] with a median age of 40 (interquartile range [IQR], 33-47) underwent appendectomy, with a median preoperative total Mayo score of 9 [IQR, 8-11]. After 12 months, 9 patients [30%] had lasting clinical response, of whom 5 [17%] were in endoscopic remission. Pathological evaluation was possible in 28 patients. After a median of 13.0 weeks [range 7-51], pathological response was seen in 13 patients [46%], with a median decrease of 2 points [range 1-3]. Appendiceal inflammation was highly predictive of pathological response when compared with no inflammation or extensive ulcerations [85% vs 20%, p = 0.001]. CONCLUSIONS: Appendectomy was effective in one-third of therapy-refractory UC patients, with a substantial proportion of patients demonstrating complete endoscopic remission after 1 year. Pathological response was seen in almost 50% of patients and was related to active inflammation in the appendix, limited disease, and shorter disease duration. These early results suggest that there is a UC patient group that may benefit from appendectomy.

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study.

BACKGROUND: Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohn's disease. AIM: To evaluate ustekinumab trough concentrations and clinical response with exclusive subcutaneous ustekinumab induction. METHODS: Patients with Crohn's disease who initiated treatment with subcutaneous ustekinumab at a single academic centre were included in this pilot study. A dosage of 360 mg ustekinumab was given subcutaneously in divided doses; 180 mg at Week 0, 90 mg at Week 1 and 90 mg at Week 2, with corresponding ustekinumab trough concentrations assessed to Week 8. The primary outcome measures were trough serum ustekinumab levels and clinical remission at Week 8. Secondary outcome measures were trough serum ustekinumab levels at Week 1 & 2 and changes in C-reactive protein, albumin and faecal calprotectin at Week 8. RESULTS: Nineteen patients were included. Median Week 8 ustekinumab trough concentrations were 6.1 µg/mL (Inter-quartile range 4-9.8 µg/mL). There was a significant improvement in Harvey Bradshaw index from Week 0 (median HBI 5; interquartile range 2-8) to Week 8 (median HBI 1; interquartile range 0-3) (P = 0.002). C-reactive protein levels did not change significantly but faecal calprotectin improved significantly; median faecal calprotectin at Week 0 was 533 µg/g; at Week 8, it was 278 µg/g (P = 0.038). CONCLUSIONS: Ustekinumab trough concentrations are comparable whether ustekinumab induction treatment was administered subcutaneously or intravenously. A significant improvement in symptoms and faecal calprotectin was noted. These results support the use of subcutaneous induction as an alternative if there are barriers to intravenous induction.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Increased non-melanoma skin cancer risk in young patients with inflammatory bowel disease on immunomodulatory therapy: a retrospective single-centre cohort study.

BACKGROUND: Recent studies report an increased risk of non-melanoma skin cancer (NMSC) in immunosuppressed patients with inflammatory bowel disease (IBD). Concurrently, paediatric IBD incidence is rising, with more patients now exposed to immunomodulators from a younger age. OBJECTIVES: To investigate NMSC incidence and to examine the risk associated with immunomodulators in the development of NMSC in patients with IBD. METHODS: This was a retrospective single-centre cohort study. Patients with IBD attending a tertiary adult hospital from 1994 to 2013 were included. Skin cancer incidence was compared with population data from the National Cancer Registry of Ireland (NCRI) to calculate standardized incidence ratio (SIR). Logistic regression was utilized for risk factor analysis. RESULTS: Two thousand and fifty-three patients with IBD were studied. The SIR for NMSC in patients with IBD taking immunomodulators overall was 1.8 (95% CI: 1.0-2.7) with age-specific rates significantly elevated across certain age categories. Exposure to thiopurines (OR: 5.26, 95% CI: 2.15-12.93, P < 0.001) and in particular thiopurines and/or tumour necrosis factor alpha (TNF-α) inhibitors (OR: 6.45, 95% CI: 2.69-15.95, P < 0.001) was significantly associated with NMSC. The majority (82%) of those exposed to a TNF-α inhibitor also had thiopurine exposure. CONCLUSIONS: Compliance with skin cancer preventative measures should be highlighted to all patients with IBD. There should be a low threshold for dermatology referral for immunosuppressed patients, particularly those with a history of exposure to dual immunomodulators from a young age.

Approach to the Synthesis of the C1-C11 and C14-C18 portion of Leucascandrolide A.

An asymmetric synthesis of the C1 to C11 and C14 to C18 fragments of the macrocyclic portion of the antibiotic Leucascandrolide A was achieved in 21 total steps from an achiral dienoate. The key 4-hydroxy-2,5-pyran portion of the natural product was established by oxy-Michael cyclization of a 5,7,9,11-tetraol intermediate, which in turn was established by an iterative asymmetric-hydration of dienoates. Alternative strategies for establishing the polyol stereochemistry were explored.

A randomized controlled trial of an internet-delivered treatment: Its potential as a low-intensity community intervention for adults with symptoms of depression.

BACKGROUND: Internet-delivered treatments for depression have proved successful, with supported programs offering the potential for improved adherence and outcomes. Internet interventions are particularly interesting in the context of increasing access to interventions, and delivering interventions population-wide. METHODS: The study was a randomized controlled trial of an 7-module internet-delivered cognitive behavioral therapy (iCBT) program for adults with depressive symptoms (n = 96) compared to a waiting-list control group (n = 92). Participants received weekly support from a trained supporter. The primary outcome was depressive symptoms as measured by the Beck Depression Inventory (BDI-II). The program was made available nationwide from an established and recognized charity for depression. RESULTS: For the treatment group, post-treatment effect sizes reported were large for the primary outcome measure (d = 0.91). The between-group effects were moderate to large and statistically significant for the primary outcomes (d = 0.50) favoring the treatment group. Gains were maintained at 6-month follow-up. CONCLUSION: The study has demonstrated the efficacy of the internet-delivered Space from Depression treatment. Participants demonstrated reliable and statistically significant changes in symptoms from pre-to post-intervention. The study supports a model for delivering online depression interventions population-wide using trained supporters. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN03704676. http://dx.doi.org/10.1186/ISRCTN03704676.

Subclassification of small bowel Crohn's disease using magnetic resonance enterography: a review using evidence-based medicine methodology.

Magnetic resonance enterography (MRE) has a growing role in imaging small bowel Crohn's disease (SBCD), both in diagnosis and assessment of treatment response. Certain SBCD phenotypes respond well to biologic therapy and others require surgery; MRE has an expanding role in triaging these patients. In this review, we evaluate the MRE signs that subclassify SBCD using evidence-based medicine (EBM) methodology and provide a structured approach to MRE interpretation.

Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer: Diagnostic and therapeutic potential.

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC.

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers.

OBJECTIVES: The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS: Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.

BACKGROUND: Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs. METHODS: Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA. RESULTS: TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs. CONCLUSION: Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC.