Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Gastric Cancer and Paraneoplastic Pemphigus

Paraneoplastic pemphigus is a relatively rare but significant acquired autoimmune mucocutaneous disorder that is characterised by diffuse erythema, painful blistering and sores of the skin and mucus membranes. The underlying pathogenesis is believed to be triggered by altered immune system in response to underlying neoplasm. The manifestations can predate, occur at the same time or after the diagnosis of cancer. Associations with gastric cancer have only been reported twice. A 78-year-old lady presented with a month’s history of extensive skin lesions that started off as bullous lesions and biopsy revealed bullous pemphigus. Endoscopy for anemia revealed gastric cancer. This case reinforced the need to consider underlying malignancy in elderly patient with new onset dermatological presentation.     

Bidirectional relationships between future time perspective and alcohol use: an exploratory study in a clinical setting

Abstract

Gaining a better grasp on factors related to changes in alcohol use is of particular interest for clinicians. Past research has highlighted a negative link between future time perspective (i.e. a disposition guiding how individuals consider and act regarding their future) and alcohol misuse. However, much remains at stake in the understanding of this association. The objective of this research was to explore bidirectional relationships between future time perspective and severity of alcohol-related problems, in a clinical setting. The sample includes 79 patients followed up in an outpatient alcohol treatment centre. Two measurement times were planned: at entry into care and 6 months later. Multiple linear regression analyses were carried out, controlling for sociodemographic variables. We found that baseline future time perspective predicted level of alcohol-related problems after 6 months in treatment, even when effects of baseline alcohol-related problems and sociodemographic variables were controlled. This study shows that the way patients see and position themselves regarding their future can affect level of alcohol-related problems. It may be useful for clinicians to identify patients with low future time perspective to offer tailored interventions and consider this dimension as a resource for change.     

Maîtrise des risques liés à la production des fluides de dialyse dans une unité de télédialyse

Objective

The “Centre Hospitalier Francois Dunan” is located on an isolated island and ensures patients care in hemodialysis thanks to telemedicine support. Many research studies have demonstrated the importance of hemodialysis fluids composition to reduce morbidity in patients on chronic hemodialysis. The aim of this study was to identify the risks inherent in the production of dialysis fluids in a particular context, in order to set up an improvement action plan to improve risk control on the production of dialysis fluids.

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.Subject terms: Immunotherapy, Melanoma