Postgraduate medical journal
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Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, the emergence of ICI-associated myocarditis (ICI-MC) presents a severe and potentially fatal complication with poorly understood pathophysiological mechanisms. This study aimed to identify crucial immune-related genes in ICI-MC and uncover potential therapeutic targets using bioinformatics. ⋯ KG7, GZMH, and KLRB1 were identified as pivotal immune-related genes in ICI-MC. Biological enrichments included pathways involved in cell lysis, the CD8+ T-cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory responses. The ceRNA network illuminated the role of critical molecules and underscored the importance of avoiding drugs such as acetohydroxamic acid in ICI treatment. Key message What is already known on this topic Myocarditis is recognized as a serious ICI-associated toxicity, seemingly infrequent yet often fulminant and lethal. The underlying mechanisms of ICI-associated myocarditis remain not fully understood. Although the significance of T cells and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is evident, the inciting antigens, the reasons for their recognition, and the mechanisms causing cardiac cell injury are not well characterized. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems. What this study adds Our study further validates the significance of T cells and CTLA-4 in ICI-associated myocarditis. More importantly, we identified three genes-NKG7, GZMH, and KLRB1-essential for the development of ICI-MC and proposed ceRNA networks involving these three key genes. How this study might affect research, practice or policy The newly discovered key genes and their intricate molecular interactions offer a comprehensive perspective on the mechanisms underlying ICI-MC. Furthermore, our findings advise caution regarding the use of drugs like acetohydroxamic acid during ICI treatment. As our understanding of these regulatory networks deepens, our study provides valuable insights that could inform future therapeutic strategies for ICI-MC.
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Chronic constipation is a prevalent clinical condition. Its etiology and pathogenesis have not yet been fully understood. ⋯ In this review, we summarize the current research insights into the intricate relationships between chronic constipation and the gut microbiota and briefly discuss several different approaches for treating chronic constipation. The findings from this review may advance our understanding of the pathological mechanisms underlying chronic constipation and, ultimately, translate them into improvements in patient care.
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To describe critical tasks and errors associated with intercostal chest drain insertion, in order to develop enhanced procedural guidelines for task performance and training. ⋯ Tasks and sub-tasks associated with intercostal chest drain insertion was described and evaluated for criticality. The most critical task was the correct identification of a safe insertion point. Applications include development of procedural guidelines with tasks vulnerable to error highlighted and training interventions that promotes safe task performance.
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Several studies demonstrated potential associations between the telomere length (TL) in leukocytes and psoriasis or psoriatic arthritis (PsA). This study aimed to investigate whether there was the causal genetic relationship between TL and psoriatic diseases bidirectionally. ⋯ This MR study revealed an association between genetic indicators of shortened TL and risk of overall psoriasis and PV, and genetic predisposition to PsA was associated with longer TL. Key message What is already known on this topic? Telomere length (TL) is acknowledged to reflect an individual's biological age but is also associated with dysregulated immune function and immunosenescence. The impact of aging on psoriasis is controversial. Existing evidence suggests that aging may influence pathological changes and clinical course but whether aging is an independent risk factor remains unclear. What this study adds? The current study found an association between genetic indicators of shortened TL and the risk of overall psoriasis and psoriasis vulgaris (PV). There was a bidirectional link between genetically indicated overall psoriasis and shortened TL. A possible positive genetic association between PsA and TL was also found. How this study might affect research, practice, or policy? Our study may provide evidence for TL as new diagnostic and therapeutic strategies in clinical practices for psoriasis. Greater efforts to psoriasis management may substantially reduce the aging attributable to TL shortening. Future large-scale GWAS and experimental studies are warranted to examine the mechanistic basis for links between TL and psoriasis to improve understanding and illuminate possible therapeutic targets for psoriatic disease.