3 research outputs found
Application of short-term analysis of skin temperature variability in prediction of survival in patients with cirrhosis
BACKGROUND: : Liver cirrhosis is a complex disorder, involving several different organ
systems and physiological network disruption. Various physiological markers have
been developed for survival modelling in patients with cirrhosis. Reduction in heart
rate variability and skin temperature variability have been shown to predict
mortality in cirrhosis, with the potential to aid clinical prognostication. We have
recently reported that short-term skin temperature variability analysis can predict
survival independently of the severity of liver failure in cirrhosis. However, in
previous reports, 24-h skin temperature recordings were used, which are often
not feasible in the context of routine clinical practice. The purpose of this study
was to determine the shortest length of time from 24-h proximal temperature
recordings that can accurately and independently predict 12-month survival postrecording in patients with cirrhosis. METHODS: Forty individuals diagnosed with cirrhosis participated in this study and wireless temperature sensors (iButtons) were used to record patients’ proximal
skin temperature. From 24-h temperature recordings, different length of
recordings (30 min, 1, 2, 3 and 6 h) were extracted sequentially for
temperature variability analysis using the Extended Poincaré plot to quantify
both short-term (SD1) and long-term (SD2) variability. These patients were
then subsequently followed for a period of 12 months, during which data was
gathered concerning any cases of mortality. RESULTS: Cirrhosis was associated with significantly decreased proximal skin
temperature fluctuations among individuals who did not survive, across all
durations of daytime temperature recordings lasting 1 hour or more. Survival
analysis showcased 1-h daytime proximal skin temperature time-series to be
significant predictors of survival in cirrhosis, whereby SD2, was found to be
independent to the Model for End-Stage Liver Disease (MELD) score and thus,
the extent of disease severity. As expected, longer durations of time-series were
also predictors of mortality for the majority of the temperature variability indices. CONCLUSION: Crucially, this study suggests that 1-h proximal skin temperature
recordings are sufficient in length to accurately predict 12-month survival in
patients with cirrhosis, independent from current prognostic indicators used in
the clinic such as MELD
The Oncolytic Adenovirus Delta-24-RGD in Combination With ONC201 Induces a Potent Antitumor Response in Pediatric High-Grade and Diffuse Midline Glioma Models
BACKGROUND: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.
METHODS: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining.
RESULTS: The Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype.
CONCLUSIONS: The Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone
Application of short-term analysis of skin temperature variability in prediction of survival in patients with cirrhosis
10.3389/fnetp.2023.1291491Frontiers in Network Physiology