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Introduction Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact. Data sources A literature review was carried out using Pubmed. Keywords used for search were ‘ATMP’, ‘immune mediated’, ‘autoimmune liver disease’ and ‘immune mediated gastrointestinal conditions’, ‘cell therapy’, ‘MSC’, ‘HSCT’, ‘Regulatory T cells’, ‘GVHD’, ‘Coeliac disease’ ‘IBD’, ‘PSC’, ‘AIH’, ‘PBC’. No new data were generated or analysed in support of this review. Areas of agreement There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to ‘reset’ the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications. Areas of controversy There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data. Growing points MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies. Areas timely for developing research Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further.

Over the last decade, there has been a considerable progress in the development of cell therapy products for the treatment of liver diseases. The quest to generate well-defined homogenous cell populations with defined mechanism(s) of action has enabled the progression from use of autologous bone marrow stem cells comprising of heterogeneous cell populations to allogeneic cell types such as monocyte-derived macrophages, regulatory T cells, mesenchymal stromal cells, macrophages, etc. There is growing evidence regarding the multiple molecular mechanisms pivotal to various therapeutic effects and hence, careful selection of cell therapy product for the desired putative effects is crucial. In this review, we have presented an overview of the cell therapies that have been developed thus far, with preclinical and clinical evidence for their use in liver disease. Limitations associated with these therapies have also been discussed. Despite the advances made, there remain multiple challenges to overcome before cell therapies can be considered as viable treatment options, and these include larger scale clinical trials, scalable production of cells according to good manufacturing practice standards, pathways for delivery of cell therapy within hospital environments, and costs associated with the production.

Alcoholic hepatitis (AH) is the dramatic acute presentation of alcoholic liver disease, with a 15% mortality rate within 28 days in severe cases. Research into AH has been hampered by the lack of effective and reproducible murine models that can be operated under different regulatory frameworks internationally. The liquid Lieber-deCarli (LdC) diet has been used as a means of ad libitum delivery of alcohol but without any additional insult, and is associated with relatively mild liver injury. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) protects against oxidative stress, and mice deficient in this molecule are suggested to be more sensitive to alcohol-induced injury. We have established a novel model of AH in mice and compared the nature of liver injury in C57/BL6 wild-type (WT) versus Nrf2−/− mice. Our data showed that both WT and Nrf2−/− mice demonstrate robust weight loss, and an increase in serum transaminase, steatosis and hepatic inflammation when exposed to diet and ethanol. This is accompanied by an increase in peripheral blood and hepatic myeloid cell populations, fibrogenic response and compensatory hepatocyte regeneration. We also noted characteristic disturbances in hepatic carbohydrate and lipid metabolism. Importantly, use of Nrf2−/− mice did not increase hepatic injury responses in our hands, and female WT mice exhibited a more-reproducible response. Thus, we have demonstrated that this simple murine model of AH can be used to induce an injury that recreates many of the key human features of AH – without the need for challenging surgical procedures to administer ethanol. This will be valuable for understanding of the pathogenesis of AH, for testing new therapeutic treatments or devising metabolic approaches to manage patients whilst in medical care. This article has an associated First Person interview with the joint first authors of the paper., Summary: We describe a simple murine model of alcoholic hepatitis (AH) to induce injury that recreates many of the key features of AH in human, without the need of challenging surgical procedures to administer ethanol. This will be valuable for testing new therapeutic treatments.

Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk.

Jaundice is a clinical sign that reflects accumulation of bilirubin in blood. It can result from increased bilirubin production, inability of the liver to conjugate bilirubin or failure to excrete bilirubin into the biliary tree. Appropriate investigation of jaundice starts with a history of associated symptoms, and risk factors for liver disease. Clinical examination should look for stigmata of chronic liver disease and signs of specific liver diseases. Initial blood tests should assess liver injury and synthetic function. A combination of urinalysis and the pattern of abnormal liver function tests can indicate whether the jaundice is likely to be hepatitic or cholestatic, and guide further investigations. This review will describe bilirubin metabolism, the causes of jaundice, and the appropriate investigation of jaundice.

Nonalcoholic fatty liver disease (NAFLD) has an estimated prevalence of 25% in the general population, and cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is predicted to become the leading cause of liver transplantation, yet there is a lack of effective licensed treatments for these conditions. There is a close relationship between insulin resistance (IR) and NAFLD, with prevalence of NAFLD being 5-fold higher in patients with diabetes compared to those without. IR is implicated both in pathogenesis of NAFLD and in disease progression from steatosis to NASH. Thus, modulation of IR represents a potential strategy for NAFLD treatment. This review highlights key proposed mechanisms linking IR and NAFLD, such as changes in rates of adipose tissue lipolysis and de novo lipogenesis, impaired mitochondrial fatty acid β-oxidation (FAO), changes in fat distribution, alterations in the gut microbiome, and alterations in levels of adipokines and cytokines. Furthermore, this review will discuss the main pharmacological strategies used to treat IR in patients with NAFLD and their efficacy based on recently published experimental and clinical data. These include biguanides, glucagon-like peptide 1 receptor (GLP-1) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, sodium glucose cotransporter 2 (SGLT2) inhibitors, and farnesoid X receptor (FXR) agonists, with further novel treatments on the horizon. Ideally, treatment would improve IR, reduce cardiovascular risk, and produce demonstrable improvements in NASH histology-this is likely to be achieved with a combinatorial approach.

In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies.

Background Continuing medical education and objective performance assessment remain the key components of recertification. Objective skills assessment in routine practice remains challenging due to extensive variations in case selection and treatments. This study explores expert opinions regarding objective skills assessment for specialists within the framework of recertification. Methods We used a qualitative, semi-structured interview-based approach to obtain information and suggestions about key issues and recommendations relating to specialists' skills assessment. Twenty-two face-to-face interviews were conducted. Interviews were transcribed and analysed by two reviewers. Results The information from the interviews was categorized under the headings of: (1) the components of specialist-level skills, (2) the methods for assessing specialist skills, (3) the types of tools and procedures used during observational assessment, (4) the unsuccessful specialists, and (5) the selection and training of assessors for specialist assessment. Conclusions Outcome-based assessment of performance followed by observation of practice, were recommended as effective modes of evaluation of performance.

What's known on the subject? and What does the study add? Dedicated training hours for surgeons are falling as the complexity of techniques and patient expectations are increasing. Urologists therefore need to train in more sophisticated and effective ways. This article looks at past and current urological training and suggests emerging and innovative ways to teach the next generation of urologists. Since 2004 the estimated available training time, for all doctors, has dropped from 30, 000 h to ≈ 8, 000h. By decreasing the initial stages of the learning curve, medical simulation has the potential to compensate for the reduced time available to train urologists. The current urological training pathway consists of 2 years of foundation year training, 2 years of core surgical training, followed by 5 years of specialty training. Training time pressures and the expansion of treatment techniques have led to a trend towards increased sub-specialization in urology. To optimize patient care, training programmes must evolve, taking into account several key issues and in accordance with advances in urological care.

Introduction: Anatomy has been considered a core subject within the medical education curriculum. In the current setting of ever-changing diagnostic and treatment modalities, the opinion of both students and trainers is crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice. Methods: Medical students, trainees and specialist trainee doctors and specialists from the London (England) area were surveyed to investigate the how curriculum changes have affected the relevance of anatomical knowledge to clinical practice and to identify recommendations for optimum teaching methods. The survey employed 5-point Likert scales and multiple-choice questions. Where the effect of training level was statistically significant ( p < 0.05), post-hoc analysis was carried out using ManneWhitney U tests. Significance levels were modified according to the Bonferroni method. Results: Two hundred and twenty-eight individuals completed the survey giving a response rateof53%.Medicalstudents,traineesandspecialists allagreed(meanLikertscore4.51,4.79, 4.69 respectively) that knowledge of anatomy is important for medical practice. Most of the trainees (88.4%) and specialists (81.3%) used dissection to learn anatomy, but only 61.4% of medical students used this approach. Dissection was the most commonly recommended approach for learning anatomy across all the groups (41.7%e69.3%). Conclusions: Knowledge of anatomy is perceived to be important for safe clinical practice. Anatomy should be taught with other relevant system or clinical modules. Newer tools for anatomy teaching need further validation before incorporation into the curriculum.

Objectives To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. Materials and methods An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. Results In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement kappa 0.89) and they included: need for a training curriculum (inter-rater agreement kappa 0.85); identification of learning needs (kappa 0.83); development of the curriculum contents (kappa 0.81); an overview of available curricula (kappa 0.79); settings for robotic surgery training ((kappa 0.89); assessment and training of trainers (kappa 0.92); requirements for certification and patient safety (kappa 0.83); and need for a universally standardised curriculum (kappa 0.78). A training curriculum was proposed based on the above discussions. Conclusion This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.

Objective. Postoperative pain is associated with delayed discharged and recovery, reduced patient satisfaction, and increased costs. The aim of this study was to investigate the short-term association between preoperative psychological variables (pain catastrophizing, anxiety, and depression) and postoperative pain in a sample of cardiac surgery patients. Design. This is a prospective epidemiological study. Setting. This study was carried out at two Imperial College Healthcare National Health Service Trust Hospitals (St. Mary's Hospital and Hammersmith Hospital, London, UK). Subjects. Sixty-four cardiac surgery patients completed the “pain catastrophizing scale (PCS),” the “hospital anxiety and depression scale,” and the “verbal rating scale” (VRS) for pain intensity preoperatively and at 48 hours postoperatively. Analgesia consumption was recorded. Data on demographic, operative, and clinical characteristics were obtained from medical records. Outcome Measures. Pain intensity at 48 hours postoperatively. Results. Scores on the anxiety, depression, and PCSs were not significantly different between the pre- and postoperative period. In contrast, patients reported a higher level of pain intensity postoperatively (P

What's known on the subject? and What does the study add? Dedicated training hours for surgeons are falling as the complexity of techniques and patient expectations are increasing. Urologists therefore need to train in more sophisticated and effective ways. This article looks at past and current urological training and suggests emerging and innovative ways to teach the next generation of urologists. Since 2004 the estimated available training time, for all doctors, has dropped from 30, 000 h to ≈ 8, 000h. By decreasing the initial stages of the learning curve, medical simulation has the potential to compensate for the reduced time available to train urologists. The current urological training pathway consists of 2 years of foundation year training, 2 years of core surgical training, followed by 5 years of specialty training. Training time pressures and the expansion of treatment techniques have led to a trend towards increased sub-specialization in urology. To optimize patient care, training programmes must evolve, taking into account several key issues and in accordance with advances in urological care.

Background Postsurgical pain is a major cause of delayed recovery and discharge after surgery. A significant proportion of patients develop chronic postsurgical pain, which affects their quality of life. Cognitive and psychological factors are reported to play a significant role in the severity of reported postsurgical pain. High levels of catastrophizing are associated with a heightened pain experience and appear to contribute to the development of chronic pain. This article describes the concept of pain catastrophizing, its association with postsurgical pain, and its potential role in the management of postsurgical pain and postsurgical quality of life. Methods Data for this review were identified from MEDLINE, EMBASE, and PsycINFO. Reference lists of selected articles were cross-searched for additional literature. Results High catastrophizing levels were found to be associated with increased pain severity, increased incidence of development of chronic pain, and poorer quality of life after surgery. There was no consensus on the relation between catastrophizing and analgesia consumption. Conclusions Identifying and reducing catastrophizing levels can help to optimize pain management in surgical patients.

Interventional radiology is a relatively new speciality and may be referred to as “image-guided surgery without a scalpel.” Training and accreditation bodies regard interventional radiology training as being “different” from general radiology because of the additional need for dexterity and clinical acumen. Due to the multidimensional role of an interventional radiologist, a practitioner in this discipline must have a number of the competencies of anesthetists, surgeons, and radiologists. The attributes required of an interventional radiologist are akin to those required of a surgeon. This paper gives an overview of the skills required to be a competent interventional radiologist along with a succinct introduction to methods of assessment of technical and non-technical skills.