The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid‐1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)‐induced lung injury in mice. For this, adult mice pre‐treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS‐challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre‐treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre‐treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.     

Vestibular Function Measurement Devices

Vestibular function laboratories utilize a multitude of diagnostic instruments to evaluate a dizzy patient. Caloric irrigators, oculomotor stimuli, and rotational chairs produce a stimulus whose accuracy is required for the patient response to be accurate. Careful attention to everything from cleanliness of equipment to threshold adjustments determine on a daily basis if patient data are going to be correct and useful. Instrumentation specifications that change with time such as speed and temperature must periodically be checked using calibrated instruments.     

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     

A Simple Dressing Technique Following Dermofasciectomy and Full Thickness Skin Grafting of the Fingers in the Treatment of Severe Dupuytren’s Contracture

Dupuytren’s disease with severe finger contractures and recurrent contractures following previous surgery often have extensive skin involvement. In these severe cases, excision of the diseased chord along with the involved skin is a good option to reduce the risk of recurrance. The resulting skin defect can be covered with a full thickness skin graft (FTSG) or a cross finger flap. Cross finger flaps have donor finger morbidity and hence a full thickness graft is usually preferred. The FTSG extending to the midlateral margins on both sides of the finger reduces the risk of joint contracture due to graft shrinkage. Once the FTSG is sutured in place, the standard practice is to compress and secure the graft to its recipient bed with a tie-over dressing and this can be time consuming. We present a simple dressing technique to secure the FTSG without the need for a tie-over dressing.