Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma

BACKGROUND Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(cHCCCCA)is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis.AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA.METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets.Radiomics features were extracted from portal venous phase computed tomography(CT)images using the least absolute shrinkage and selection operator Cox regression and random forest analysis.A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression.Nomogram performance was assessed in terms of the C-index as well as calibration,decision,and survival curves.RESULTS CT and clinical data of 118 patients were included in the study.The radiomics score,vascular invasion,anatomical resection,total bilirubin level,and satellite lesions were found to be independent predictors of overall survival(OS)and were therefore included in an integrative nomogram.The nomogram was more strongly associated with OS(hazard ratio:8.155,95%confidence interval:4.498-14.785,P<0.001)than a model based on the radiomics score or only clinical factors.The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875,respectively.Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk(6.1 vs 81.6 mo,P<0.001).CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.

Immune checkpoint inhibitor-associated ophthalmic adverse events: current understanding of its mechanisms,diagnosis, and management

Immune checkpoint inhibitors(ICIs) targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment, achieving unprecedented efficacy in numerous malignancies. Despite the excellent therapeutic effects of ICIs, medications, such as pembrolizumab, ipilimumab, nivolumab, atezolizumab, avelumab, and durvalumab, typically cause a broad spectrum of toxicity events termed as immune-related adverse events(ir AEs). Out of all ir AEs, ophthalmic adverse events occur infrequently and are not comprehensively recognized. The current understanding of ophthalmic ir AEs is mainly derived from case reports and case series. In this review, based on relevant articles in the literature and current evidence, we summarize the incidences, manifestations, diagnoses, underlying mechanisms, treatments, and outcomes of ophthalmic ir AEs and discuss possible management strategies. A better understanding of these features is critical for managing patients with ICI-associated ophthalmic adverse events.

Therapeutic targets and interventional strategies in COVID-19:mechanisms and clinical studies

Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the lack of the understanding of the biological regulation mechanisms underlying COVID-19,alternative or novel therapeutic targets for COVID-19 treatment are still urgently required.SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19.Both the virus and host factors are potential targets for antiviral therapy.Hence,in this study,the current therapeutic strategies of COVID-19 have been classified into"target virus"and"target host" categories.Repurposing drugs,emerging approaches,and promising potential targets are the implementations of the above two strategies.First,a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians.Additionally,their unavailability in the fight against COVID-19 was analyzed.Next,a profound analysis of the emerging approaches was conducted,particularly all licensed vaccines and monoclonal antibodies(mAbs)enrolled in clinical trials against primary SARS-CoV-2 and mutant strains.Furthermore,the pros and cons of the present licensed vaccines were compared from different perspectives.Finally,the most promising potential targets were reviewed,and the update of the progress of treatments has been summarized based on these reviews.