Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.

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BackgroundAlternative splicing (AS) is a gene regulatory mechanism that drives protein diversity. Dysregulation of AS is thought to play an essential role in cancer initiation and development. This study aimed to construct a prognostic signature based on AS and explore the role in the tumor immune microenvironment (TIME) in lung adenocarcinoma.MethodsWe analyzed transcriptome profiling and clinical lung adenocarcinoma data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq. Prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analyses, and proportional hazards model. The context of TIME in lung adenocarcinoma was also analyzed. Gene and protein expression data of Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) were obtained from ONCOMINE and Human Protein Atlas. Splicing factor (SF) regulatory networks were visualized.ResultsA total of 19,054 survival-related AS events in lung adenocarcinoma were screened in 1,323 genes. Exon skip (ES) and mutually exclusive exons (ME) exhibited the most and fewest AS events, respectively. Based on AS subtypes, eight AS prognostic signatures were constructed. Patients with high-risk scores were associated with poor overall survival. A nomogram with good validity in prognostic prediction was generated. AUCs of risk scores at 1, 2, and 3 years were 0.775, 0.736, and 0.759, respectively. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. Low-risk patients had a higher StromalScore, ImmuneScore, and ESTIMATEScore. AS-based risk score signature was positively associated with CD8+ T cells. CDKN2A was also found to be a prognostic factor in lung adenocarcinoma. Finally, potential functions of SFs were determined by regulatory networks.ConclusionTaken together, our findings show a clear association between AS and immune cell infiltration events and patient outcome, which could provide a basis for the identification of novel markers and therapeutic targets for lung adenocarcinoma. SF networks provide information of regulatory mechanisms.

An intestinal stoma is a surgically formed exteriorisation of the large or small bowel on to the anterior abdomen wall, to enable faeces to be excreted from the body. Patients living with a stoma may encounter physical, psychological, and social barriers and challenges. Stoma self-management education is essential to improving self-care competence, and patients who perceive the benefits of self-management education show a better adjustment to living with a stoma. This literature review explored the effectiveness of patient education interventions in improving the self-care knowledge and skills of patients living with an ostomy. The findings from the nine studies reviewed showed that self-management education approaches are effective in improving patients' self-care. The application of different approaches to ostomy self-management education, such as a transtheoretical model, chronic care model, telehealth and multimedia-based programmes – helped improve patients' self-care ability. The review also found that patients needed at least 3 months to develop the skills and maintain their ability to self-care. In addition, two education sessions provided to patients in hospital pre-discharge appeared sufficient for improving and maintaining self-care abilities. Where patients received education in hospital post-surgery, 2 or 3 sessions over 7 days were found to be sufficient to provide them with stoma care skills. Education sessions based on the transtheoretical model and chronic care model or telehealth helped maintain and reinforce self-care behaviours following discharge.

An intestinal stoma is a surgically formed exteriorisation of the large or small bowel on to the anterior abdomen wall, to enable faeces to be excreted from the body. Patients living with a stoma may encounter physical, psychological, and social barriers and challenges. Stoma self-management education is essential to improving self-care competence, and patients who perceive the benefits of self-management education show a better adjustment to living with a stoma. This literature review explored the effectiveness of patient education interventions in improving the self-care knowledge and skills of patients living with an ostomy. The findings from the nine studies reviewed showed that self-management education approaches are effective in improving patients’ self-care. The application of different approaches to ostomy self-management education, such as a transtheoretical model, chronic care model, telehealth and multimediabased programmes – helped improve patients’ self-care ability. The review also found that patients needed at least 3 months to develop the skills and maintain their ability to self-care. In addition, two education sessions provided to patients in hospital pre-discharge appeared sufficient for improving and maintaining self-care abilities. Where patients received education in hospital post-surgery, 2 or 3 sessions over 7 days were found to be sufficient to provide them with stoma care skills. Education sessions based on the transtheoretical model and chronic care model or telehealth helped maintain and reinforce self-care behaviours following discharge.