Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor.

Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care.

Enhancing self-care education amongst medical students: a systematic scoping review.

BACKGROUND: Reports of emotional, existential and moral distress amongst medical students witnessing death and suffering of patients during their clinical postings have raised awareness on the need for better psycho-emotional support during medical school. Furthermore, the stress experienced by medical students stemming from the rigours of their academic curriculum underlines the need for greater awareness on mental health issues and better self-care practices across medical training. With such programmes lacking in most medical schools, we propose a systematic scoping review (SSR) to map and address our research question, "what is known about self-care education interventions amongst medical students?". METHODS: We adopted the Systematic Evidence-Based Approach to guide a systematic scoping review (SSR in SEBA) of relevant articles published between 1st January 2000 and 30th June 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles were independently and concurrently thematically and content analysed, with complementary categories and themes combined using the Jigsaw Approach. The domains created from the Funnelling Process framed the discussion. RESULTS: A total of 6128 abstracts were identified, 429 full-text articles evaluated, and 147 articles included. The 6 domains identified were definition, topics, pedagogy, influences, outcomes and assessment. Most interventions were promising, though peer-led mindfulness-based interventions showed most promise in enhancing engagement, positively impacting personal wellbeing, and improving patient care. Overall, however, self-care education was poorly recognized, adopted and integrated into curricula. CONCLUSION: Greater dedicated time and conducive practice environments within medical school curricula is required to enhance medical student wellbeing. Host organizations must ensure faculty are appropriately selected to instil the importance of self-care, be trained to assess and personalize self-care interventions and provide longitudinal assessment and support. Further study into assessing self-care capabilities is required.

Pathogenesis and therapeutic implications of EBV-associated epithelial cancers.

Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.

Preoperative shock index in major abdominal emergency surgery.

Introduction: Major abdominal emergency surgery (MAES) patients have a high risk of mortality and complications. The time-sensitive nature of MAES necessitates an easily calculable risk-scoring tool. Shock index (SI) is obtained by dividing heart rate (HR) by systolic blood pressure (SBP) and provides insight into a patient's haemodynamic status. We aimed to evaluate SI's usefulness in predicting postoperative mortality, acute kidney injury (AKI), requirements for intensive care unit (ICU) and high-dependency monitoring, and the ICU length of stay (LOS). Method: We retrospectively reviewed 212,089 MAES patients from January 2013 to December 2020. The cohort was propensity matched, and 3960 patients were included. The first HR and SBP recorded in the anaesthesia chart were used to calculate SI. Regression models were used to investigate the association between SI and outcomes. The relationship between SI and survival was explored with Kaplan-Meier curves. Results: There were significant associations between SI and mortality at 1 month (odds ratio [OR] 2.40 [1.67-3.39], P<0.001), 3 months (OR 2.13 [1.56-2.88], P<0.001), and at 2 years (OR 1.77 [1.38-2.25], P<0.001). Multivariate analysis revealed significant relationships between SI and mortality at 1 month (OR 3.51 [1.20-10.3], P=0.021) and at 3 months (OR 3.05 [1.07-8.54], P=0.034). Univariate and multivariate analysis also revealed significant relationships between SI and AKI (P<0.001), postoperative ICU admission (P<0.005) and ICU LOS (P<0.001). SI does not significantly affect 2-year mortality. Conclusion: SI is useful in predicting postopera-tive mortality at 1 month, 3 months, AKI, postoperative ICU admission and ICU LOS.

Epstein-Barr Virus Epithelial Cancers-A Comprehensive Understanding to Drive Novel Therapies.

Epstein-Barr virus (EBV) is a ubiquitous oncovirus associated with specific epithelial and lymphoid cancers. Among the epithelial cancers, nasopharyngeal carcinoma (NPC), lymphoepithelioma-like carcinoma (LELC), and EBV-associated gastric cancers (EBVaGC) are the most common. The role of EBV in the pathogenesis of NPC and in the modulation of its tumour immune microenvironment (TIME) has been increasingly well described. Much less is known about the pathogenesis and tumour-microenvironment interactions in other EBV-associated epithelial cancers. Despite the expression of EBV-related viral oncoproteins and a generally immune-inflamed cancer subtype, EBV-associated epithelial cancers have limited systemic therapeutic options beyond conventional chemotherapy. Immune checkpoint inhibitors are effective only in a minority of these patients and even less efficacious with molecular targeting drugs. Here, we examine the key similarities and differences of NPC, LELC, and EBVaGC and comprehensively describe the clinical, pathological, and molecular characteristics of these cancers. A deeper comparative understanding of these EBV-driven cancers can potentially uncover targets in the tumour, TIME, and stroma, which may guide future drug development and cast light on resistance to immunotherapy.