Bmc Med
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Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil. ⋯ There was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers.
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The combination of oncolytic viruses (OVs) with immune checkpoint blockades is a research hotspot and has shown good efficacy. Here, we present the first attempt to combine oncolytic herpes simplex virus 2 (OH2) with an anti-SIRPα antibody as an antitumour treatment. Our results provide unique insight into the combination of innate immunity with OV. ⋯ Our data support the feasibility of oncolytic virus therapy in combination with anti-SIRPα antibodies and suggest a new strategy for oncolytic virus therapy.
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Though the association between air pollution and incident type 2 diabetes (T2D) has been well documented, evidence on the association with development of subsequent diabetes complications and post-diabetes mortality is scarce. We investigate whether air pollution is associated with different progressions and outcomes of T2D. ⋯ This study indicates that ambient air pollution exposure may contribute to increased risk of incidence and progressions of T2D, but to diverse extents for different progressions.
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Pragmatic trials aim to generate evidence to directly inform patient, caregiver and health-system manager policies and decisions. Heterogeneity in patient characteristics contributes to heterogeneity in their response to the intervention. However, there are many other sources of heterogeneity in outcomes. Based on the expertise and judgements of the authors, we identify different sources of clinical and methodological heterogeneity, which translate into heterogeneity in patient responses-some we consider as desirable and some as undesirable. For each of them, we discuss and, using real-world trial examples, illustrate how heterogeneity should be managed over the whole course of the trial. ⋯ Heterogeneity in centres and patients should be welcomed rather than limited. Interventions can be flexible or tailored and control interventions are expected to reflect usual care, avoiding use of a placebo. Co-interventions should be allowed; adherence should not be enforced. All these elements introduce heterogeneity in interventions (experimental or control), which has to be welcomed because it mimics reality. Outcomes should be objective and possibly routinely collected; standardised assessment, blinding and adjudication should be avoided as much as possible because this is not how assessment would be done outside a trial setting. The statistical analysis strategy must be guided by the objective to inform decision-making, thus favouring the intention-to-treat principle. Pragmatic trials should consider including process analyses to inform an understanding of the trial results. Needed data to conduct these analyses should be collected unobtrusively. Finally, ethical principles must be respected, even though this may seem to conflict with goals of pragmatism; consent procedures could be incorporated in the flow of care.
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The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. ⋯ Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.