Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles.

BACKGROUND: Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. METHODS: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. RESULTS: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10-6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. CONCLUSIONS: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.

Regional survey of foundation trainee doctors' views on a career in gastroenterology: implications for diversity and inclusion.

Objective: We aimed to establish the perception of foundation doctors (FDs) towards gastroenterology, focusing on identifying determinants which make the career desirable or undesirable between genders, and to recognise factors to increase diversity in recruitment. Method: An electronic survey was circulated to Northwest of England FDs, categorical variables and data were analysed using χ2 test including comparisons by gender and exposure to gastroenterology either as an undergraduate or FD. Results: 133 responses were received (males 55.6%, 37 foundation year 1 (FY1) doctors, 85 FY2 doctors and 11 FY3 doctors). Four (3.0%) FDs were considering a career in gastroenterology. Gastroenterology was perceived positively by 72 (54.1%) of FDs. Significant differences were found between genders in the importance of the following factors influencing specialty selection; patient-centred care (female 52.5% vs male 25.7%, p=0.01), good mentorship (female 67.8% vs male 45.9, p=0.012), income (female 33.9% vs male 59.5%, p=0.003) and length of training (female 27.1% vs male 52.7%, p=0.003). The male predominant existing workforce (female 27.1% vs male 6.8%, p=0.001), and requirement to be a medical registrar (female 74.6% vs male 56.8%, p=0.033) were negatively perceived aspects of gastroenterology among female FDs. Most FDs (female 80.5%, male 70.7%) indicated increased acceptability of less than full time training and greater flexibility may attract more females to gastroenterology. Conclusion: Increased flexibility in training and greater postfoundation exposure and mentorship may improve diversity within the specialty. The role of general medicine poses significant concern for FDs and may need further evaluation.

Value of Drains in Soft-Tissue Tumour Surgery: A Specialist Regional Centre Experience.

Background The mainstay of therapy in most soft-tissue tumours (STTs) is excision. However, this often results in blood/extracellular fluid collection within large dead spaces necessitating the use of surgical drains. Whether meticulous attention to haemostasis, careful closure of dead space, and use of compression bandage obviates the need for drains was investigated. This study aimed to compare postoperative outcomes in patients undergoing surgery for STTs with and without the use of drains. Methodology A retrospective analysis of patients undergoing STT surgery over five years was undertaken using a regional STT specialist service database. Patients were stratified into the following two groups: compression bandage alone (CB) versus compression bandage with drain (CBD). The chi-square test was used to examine associations with infection, seroma, and haematoma, while the unpaired t-test was used for associations with hospital stay and time to wound healing. The unpaired t-test with Bonferroni correction was used to account for tumour dimensions across both groups. Results A total of 81 CB and 25 CBD patients were included. The mean hospital stay was significantly lower in CB compared to CBD (4.9 days, SD = 8.574 vs. 9.8 days, SD = 7.647, p = 0.0125). None of the other variables was significantly different between the two groups, including infection (21.3% vs. 24.0%, p = 0.7804), seroma (25.0% vs. 36.0%, p = 0.2865), haematoma (0.026% vs. 2.0%, p = 0.2325), and time to wound healing (55.8 days, SD = 63.59 vs. 42.3 days, SD = 58.88, p = 0.3648). Conclusions Our findings suggest that the use of drains in patients undergoing STT tumour surgery lengthens hospital stay without reducing the incidence of postoperative complications/time to wound healing. A larger, prospective trial is needed.