Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC

META-ANALYSIS OF MEDICAL AND NON-MEDICAL TREATMENTS OF THE PRODROMAL PHASE OF PSYCHOTIC ILLNESS IN AT-RISK MENTAL STATES

Introduction: There are now many existing studies which assess the treatments available for ‘at risk mental states’, as patients who are believed to be in the prodromal phase of psychotic illness are referred to. However, concerns regarding side effects of possible treatments remain. We here conduct a meta-analysis of the studies available up to October 2010. The aim of this study is to decide what would be the best treatment for ‘at high risk patients’. Results: All the available studies examining potential treatments during the prodromal phase of psychotic illness were collected. They all showed comparable efficacy, which reached statistical significance, excluding the one study using olanzapine, which in fact ‘tended towards significance’. Discussion: Treatments appear promising but a balance needs to be kept between adverse events and effectiveness of preventing psychosis. Conclusion: It is necessary to search further for treatments in order to identify effective treatments with fewer adverse side effects in this phase of psychotic illness

AN UPDATE ON: META-ANALYSIS OF MEDICAL AND NON-MEDICALTREATMENTS OF THE PRODROMAL PHASE OF PSYCHOTIC ILLNESS IN AT RISK MENTAL STATES

Introduction: There are now many existing studies which assess the treatments available for ‘at risk mental states’, as patients who are believed to be in the prodromal phase of psychotic illness are referred to. However, concerns regarding side effects of possible treatments remain. We here conduct a meta-analysis of the studies available up to July 2016. The aim of this study is to decide what would be the best treatment for ‘at high risk patients’. Results: 18 studies were selected for inclusion; 12 showed significance, 5 did not and one tended towards significance. Both antipsychotic medication and psychological intervention show mixed results with cognitive behavioral therapy and olanzapine/amisulpride coming out on top. Omega 3 poly-unsaturated acid also shows promising and consistent results. Discussion: Treatments appear promising but a balance needs to be kept between adverse events and effectiveness of preventing psychosis. Conclusion: It is necessary to search further for treatments in order to identify effective treatments with fewer adverse sideeffects in this phase of psychotic illness

Lynch syndrome: from detection to treatment

Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations

Molecular beacon-based real-time PCR detection of primary isolates of Salmonella Typhimurium and Salmonella Enteritidis in environmental and clinical samples

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background A fast and simple two-step multiplex real-time PCR assay has been developed to replace the traditional, laborious Salmonella serotyping procedure. Molecular beacons were incorporated into the assay as probes for target DNA. Target sequences were regions of the invA, prot6E and fliC genes specific for Salmonella spp. Salmonella Enteritidis and Salmonella Typhimurium, respectively, the two most clinically relevant serotypes. An internal amplification positive control was included in the experiment to ensure the optimal functioning of the PCR and detect possible PCR inhibition. Three sets of primers were used for the amplification of the target sequences. The results were compared to those of the Kauffmann-White antigenic classification scheme. Results The assay was 100% sensitive and specific, correctly identifying all 44 Salmonella strains, all 21 samples of S. Enteritidis and all 17 samples of S. Typhimurium tested in this work. Therefore, the entire experiment had specificity and sensitivity of 100%. The detection limit was down to 10 copies of DNA target per 25 μl reaction. Conclusion The assay can amplify and analyse a large number of samples in approximately 8 hours, compared to the 4 to 5 days conventional identification takes, and is thus considered a very promising method for detecting the two major serotypes of Salmonella quickly and accurately from clinical and environmental samples.Published versio

DOES EARLY INTERVENTION FOR PSYCHOSIS WORK? An analysis of Outcomes of Early Intervention in Psychosis based on the Critical Period Hypothesis, Measured by Number of Admissions and Bed Days Used over a period of Six Years, the first three in an Early Intervention Service, The second Three in a Community Mental Health Team

Background: Early Intervention in Psychosis (EI) was introduced into the British NHS as a result of the NHS Plan, about eleven years ago. The intention was to provide thebest possible care or patients with a first episode of psychosis.Recently however, long term studies over five years have suggested that early gains may be lost. Methods and Aims: We wished to establish whether our own group of patients who had received Early Intervention continued over six years to have better outcomes than patients treated in Community Mental Health Teams. To do this we analysed statistically the data on the readmissions and bed days used by our patients over the first six years of illness. Results: We found that patients, both in the whole two groups and in different sub-groups appeared to demonstrate a number of advantages,not always statistically significant, in favour of the EI treated team. Discussion: In many cases, the small size of the samples may have impeded us observing statistically significant differences, however, in general, it appeared that there were a number of advantages in favour of the EI treated team. Conclusion: Our study, though small, does appear to support the view that Early Intervention Services do improve outcomes and that some of the improvement may endure after the patient leaves EI services. Much larger studies ae however required

Standard versus simplified radiofrequency ablation protocol for Barrett's esophagus: comparative analysis of the whole treatment pathway.

Background and study aims  The standard radiofrequency ablation (RFA) protocol for Barrett's esophagus (BE) encompasses an intermediary cleaning phase between two ablation sessions. A simplified protocol omitting the cleaning phase is less labor-intensive but equally effective in studies based on single ablation procedures. The aim of this study was to compare efficacy and safety of the standard and simplified RFA protocols for the whole treatment pathway for BE, including both circumferential and focal devices. Patients and methods  We performed a retrospective analysis of prospectively collected data on patients receiving RFA between January 2007 and August 2017 at two institutions. Outcomes assessed were: 1) complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) at 18 months; and 2) rate of esophageal strictures. Results  One hundred forty-five patients were included of whom 73 patients received the standard and 72 patients received the simplified protocol. CR-D was achieved in 94.5 % and 95.8 % of patients receiving the standard and simplified protocol, respectively ( P  = 0.71). CR-IM was achieved in 84.9 % and 77.8 % of patients treated with the standard and simplified protocol, respectively ( P  = 0.27). Strictures were significantly more common among patients who received the simplified protocol (12.5 %) compared to the standard protocol (1.4 %; P  = 0.008). The median number of esophageal dilations was one. Conclusion  The simplified RFA protocol is as effective as the standard protocol in eradicating BE but carries a higher risk of strictures. This needs to be taken into account, particularly in patients with higher pretreatment risk of strictures, such as those with esophageal narrowing from previous endoscopic mucosal resection (EMR)

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC