Is socioeconomic deprivation associated with worse quality of life, anxiety and depression in liver transplant recipients? A cross-sectional study in a national transplantation programme.

OBJECTIVE: To identify whether socioeconomic deprivation is associated with worse health-related quality of life (HR-QoL), anxiety and depression following liver transplantation. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Liver transplant recipients within a national transplantation programme. METHODS: Participants completed the condition-specific 'Short Form of Liver Disease Quality of Life' Questionnaire, the Generalised Anxiety Disorder-7 (GAD-7) Questionnaire and the Patient Health Questionnaire-9 (PHQ-9). The aggregate HR-QoL Score (range 0-100) was derived, and multivariable linear regression was performed based on sociodemographic and clinical variables to estimate its independent association with Scottish Index of Multiple Deprivation (SIMD) quintiles. The GAD-7 Questionnaire and PHQ-9 were used to screen respondents for anxiety and depression, and multivariable logistic regression was performed to estimate their independent association with SIMD quintiles. RESULTS: Some 331 patients completed the questionnaires. Quintiles were equally distributed in the cohort, with no significant differences observed in underlying patient characteristics. Following multivariable adjustment, greater socioeconomic deprivation was associated with lower post-transplantation HR-QoL scores, with a difference of 9.7 points (95% CI: 4.6 to 14.9, p<0.001) between the most and least deprived quintiles. Recipients living in areas of least deprivation were less likely to suffer from anxiety (OR 0.05, 95% CI: 0.00 to 0.28, p=0.003) or depression (OR 0.13, 95% CI: 0.02 to 0.56, p=0.009). CONCLUSION: Despite the highly selected nature of liver transplant recipients, those living in the most deprived areas have a significantly lower HR-QoL and are more likely to suffer from anxiety and depression.

Educational impact and recommendations from implementation of student-led clinical trial recruitment: a mixed-methods study.

Medical students have an essential role in medical research, yet often lack opportunities for involvement within randomised trials. This study aimed to understand the educational impact of clinical trial recruitment for medical students. Tracking wound infection with smartphone technology (TWIST) was a randomised controlled trial that included adult patients undergoing emergency abdominal surgery across two university teaching hospitals. All recruiters underwent prerecruitment training based on 'Generating Student Recruiters for Randomised Trials' principles, and completed prerecruitment and postrecruitment surveys. Respondent agreement with statements were assessed using 5-point Likert scales (from 1 ('strongly disagree') to 5 ('strongly agree')). Quantitative data were analysed using paired t-tests to compare differences pre-involvement and post-involvement. Thematic content analysis was performed on free-text data to generate recommendations for future student research involvement. Of 492 patients recruited to TWIST between 26 July 2016 and 4 March 2020, 86.0% (n=423) were recruited by medical students. Following introduction of student co-investigators (n=31), the overall monthly recruitment rate tripled (4.8-15.7 patients). 96.8% of recruiters (n=30/31) completed both surveys, and all respondents reported significant improvement in clinical and academic competencies. Three higher-level thematic domains emerged from the qualitative analysis: (1) engagement, (2) preparation and (3) ongoing support. Student recruitment in clinical trials is feasible and accelerates recruitment to clinical trials. Students demonstrated novel clinical research competencies and increased their likelihood of future involvement. Adequate training, support and selection of suitable trials are essential for future student involvement in randomised trials.

The First Modified Delphi Consensus-Building Exercise on Surgical Ward Rounds in the United Kingdom National Health Service.

BACKGROUND: The ward round is an integral part of everyday surgical practice. It is a complex clinical activity that requires both sound clinical management and communication skills. This study reports the results of a consensus-building exercise on the common aspects of the general surgical ward rounds. METHODS: The consensus-building committee involving a range of stakeholders from 16 United Kingdom (UK) National Health Service trusts took part in this consensus exercise. The members discussed and suggested a series of statements concerning surgical ward round. An agreement of ≥ 70% among members was regarded as a consensus. RESULTS: Thirty-two members voted on 60 statements. There was a consensus on fifty-nine statements after the first round of voting, and one statement was modified before it reached consensus in the second round. The statements covered nine sections: a preparation phase, team allocation, multidisciplinary approach to the ward round, structure of the round, teaching considerations, confidentiality and privacy, documentation, post-round arrangements, and weekend round. There was a consensus on spending time to prepare for the round, a consultant-led round, involvement of the nursing staff, an MDT round at the beginning and end of the week, a minimum of 5 min allocated to each patient, utilisation of a round checklist, afternoon virtual round, and a clear handover and plan for the weekend. CONCLUSION: The consensus committee achieved agreement on several aspects concerning the surgical ward rounds in the UK NHS. This should help improve the care of surgical patients in the UK.

DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01.

BACKGROUND AND AIMS: Dickkopf-1 (DKK1) is associated with poor prognosis in intrahepatic cholangiocarcinoma (iCCA), but the mechanisms behind this are unclear. Here, we show that DKK1 plays an immune regulatory role in vivo and inhibition reduces tumour growth. METHODS: Various in vivo GEMM mouse models and patient samples were utilized to assess the effects of tumour specific DKK1 overexpression in iCCA. DKK1-driven changes to the tumour immune microenvironment were characterized by immunostaining and gene expression analysis. DKK1 overexpressing and damage-induced models of iCCA were used to demonstrate the therapeutic efficacy of DKK1 inhibition in these contexts using the anti-DKK1 therapeutic, DKN-01. RESULTS: DKK1 overexpression in mouse models of iCCA drives an increase in chemokine and cytokine signalling, the recruitment of regulatory macrophages, and promotes the formation of a tolerogenic niche with higher numbers of regulatory T cells. We show a similar association of DKK1 with FOXP3 and regulatory T cells in patient tissue and gene expression data, demonstrating these effects are relevant to human iCCA. Finally, we demonstrate that inhibition of DKK1 with the monoclonal antibody mDKN-01 is effective at reducing tumour burden in two distinct mouse models of the disease. CONCLUSION: DKK1 promotes tumour immune evasion in iCCA through the recruitment of immune suppressive macrophages. Targeting DKK1 with a neutralizing antibody is effective at reducing tumour growth in vivo. As such, DKK1 targeted and immune modulatory therapies may be an effective strategy in iCCA patients with high DKK1 tumour expression or tolerogenic immune phenotypes.

Systematic review and meta-analysis of survival outcomes in T2a and T2b gallbladder cancers.

BACKGROUND: The 8th edition of AJCC TNM staging of Gallbladder cancer subdivided T2 stage into T2a and T2b based on tumour location. This meta-analysis aimed to investigate the long-term outcomes in T2a and T2b gallbladder cancers. METHODS: Literature search of Medline, Web of science, Embase and Cochrane databases was performed. Study characteristics, survival and recurrence data were extracted for meta-analysis of effect estimates and of individual patient data. RESULTS: Fifteen retrospective studies (2531 patients, T2a = 1332, T2b = 199) were included in the meta-analysis. Overall survival (OS) was significantly worse in patients with T2b compared to T2a tumours (HR 2.18, 95% CI 1.67-2.86, p < 0.0001). Meta-analysis of individual patient data (n = 629) showed similar results (HR 1.92, 95% CI 1.43-2.58, p < 0.00001). Patients with T2b tumours had higher risk of recurrence compared to T2a (OR 3.19, 95% CI 1.40-7.28, p = 0.006) and were more likely to receive adjuvant chemotherapy (OR 1.76, 95% CI 1.12-2.84, p = 0.014). Liver resection improved OS in T2b tumours (HR 2.99, CI 1.73-5.16, p < 0.0001). CONCLUSION: T2b gallbladder tumours have worse overall survival and increase risk of recurrence compared to T2a. Liver resection appears to improve OS in patients with T2b tumours. However, high quality multicenter data is required to confirm these results.

Remote diagnosis of surgical-site infection using a mobile digital intervention: a randomised controlled trial in emergency surgery patients.

Surgical site infections (SSI) cause substantial morbidity and pose a burden to acute healthcare services after surgery. We aimed to investigate whether a smartphone-delivered wound assessment tool can expedite diagnosis and treatment of SSI after emergency abdominal surgery. This single-blinded randomised control trial (NCT02704897) enroled adult emergency abdominal surgery patients in two tertiary care hospitals. Patients were randomised (1:1) to routine postoperative care or additional access to a smartphone-delivered wound assessment tool for 30-days postoperatively. Patient-reported SSI symptoms and wound photographs were requested on postoperative days 3, 7, and 15. The primary outcome was time-to-diagnosis of SSI (Centers for Disease Control definition). 492 patients were randomised (smartphone intervention: 223; routine care: 269). There was no significant difference in the 30-day SSI rate between trial arms: 21 (9.4%) in smartphone vs 20 (7.4%, p = 0.513) in routine care. Among the smartphone group, 32.3% (n = 72) did not utilise the tool. There was no significant difference in time-to-diagnosis of SSI for patients receiving the intervention (-2.5 days, 95% CI: -6.6-1.6, p = 0.225). However, patients in the smartphone group had 3.7-times higher odds of diagnosis within 7 postoperative days (95% CI: 1.02-13.51, p = 0.043). The smartphone group had significantly reduced community care attendance (OR: 0.57, 95% CI: 0.34-0.94, p = 0.030), similar hospital attendance (OR: 0.76, 95% CI: 0.28-1.96, p = 0.577), and significantly better experiences in accessing care (OR: 2.02, 95% CI: 1.17-3.53, p = 0.013). Smartphone-delivered wound follow-up is feasible following emergency abdominal surgery. This can facilitate triage to the appropriate level of assessment required, allowing earlier postoperative diagnosis of SSI.

Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma.

OBJECTIVE: To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC). BACKGROUND: Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT. METHODS: MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival. RESULTS: Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%-79.4%), 48.0% (95% CI 35.0%-60.9%), and 31.6% (95% CI 23.1%-40.7%). These improved to 82.8% (95% CI 73.0%-90.8%), 65.5% (95% CI 48.7%-80.5%), and 65.1% (95% CI 55.1%-74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%-30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%-69.4%) without. CONCLUSIONS: In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.