Objective: To develop a customized short LOS (gery, using local data and a computational feature selection algorithm. Design: Utilization of a machine learning algorithm in a prospectively collected STS database consi...Objective: To develop a customized short LOS (gery, using local data and a computational feature selection algorithm. Design: Utilization of a machine learning algorithm in a prospectively collected STS database consisting of patients who received cardiac surgery between January 2002 and June 2011. Setting: Urban tertiary-care center. Participants: Geriatric patients aged 70 years or older at the time of cardiac surgery. Interventions: None. Measurements and Main Results: Predefined morbidity and mortality events were collected from the STS database. 23 clinically relevant predictors were investigated for short LOS prediction with a genetic algorithm (GenAlg) in 1426 patients. Due to the absence of an STS model for their particular surgery type, STS risk scores were unavailable for 771 patients. STS prediction achieved an AUC of 0.629 while the GenAlg achieved AUCs of 0.573 (in those with STS scores) and 0.691 (in those without STS scores). Among the patients with STS scores, the GenAlg features significantly associated with shorter LOS were absence of congestive heart failure (CHF) (OR = 0.59, p = 0.04), aortic valve procedure (OR = 1.54, p = 0.04), and shorter cross clamp time (OR = 0.99, p = 0.004). In those without STS prediction, short LOS was significantly correlated with younger age (OR = 0.93, p 0.001), absence of CHF (OR = 0.53, p = 0.007), no preoperative use of beta blockers (OR = 0.66, p = 0.03), and shorter cross clamp time (OR = 0.99, p 0.001). Conclusion: While the GenAlg-based models did not outperform STS prediction for patients with STS risk scores, our local-data-driven approach reliably predicted short LOS for cardiac surgery types that do not allow STS risk calculation. We advocate that each institution with sufficient observational data should build their own cardiac surgery risk models.展开更多
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early dia...Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles （NP）-embedded silica nanoshuttles （MGNSs） with nanopores on their surface. Fluorescently labeled Doxombicin （DOX）, a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P（NIPAM-co- MAA） to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in： （a） a glass capillary tube to simulate their delivery via blood vessels; and （b） porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier {BBB）. The viscoelastic properties of hydrogels were examined by atomic force microscopy （AFM）. Cellular uptake of DOX- loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells （iPSCs） as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells＇ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics＇ payloads and precisely guided transport in specified tissues and organs （for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain） for highly efficient personalized medicine applications.展开更多
文摘Objective: To develop a customized short LOS (gery, using local data and a computational feature selection algorithm. Design: Utilization of a machine learning algorithm in a prospectively collected STS database consisting of patients who received cardiac surgery between January 2002 and June 2011. Setting: Urban tertiary-care center. Participants: Geriatric patients aged 70 years or older at the time of cardiac surgery. Interventions: None. Measurements and Main Results: Predefined morbidity and mortality events were collected from the STS database. 23 clinically relevant predictors were investigated for short LOS prediction with a genetic algorithm (GenAlg) in 1426 patients. Due to the absence of an STS model for their particular surgery type, STS risk scores were unavailable for 771 patients. STS prediction achieved an AUC of 0.629 while the GenAlg achieved AUCs of 0.573 (in those with STS scores) and 0.691 (in those without STS scores). Among the patients with STS scores, the GenAlg features significantly associated with shorter LOS were absence of congestive heart failure (CHF) (OR = 0.59, p = 0.04), aortic valve procedure (OR = 1.54, p = 0.04), and shorter cross clamp time (OR = 0.99, p = 0.004). In those without STS prediction, short LOS was significantly correlated with younger age (OR = 0.93, p 0.001), absence of CHF (OR = 0.53, p = 0.007), no preoperative use of beta blockers (OR = 0.66, p = 0.03), and shorter cross clamp time (OR = 0.99, p 0.001). Conclusion: While the GenAlg-based models did not outperform STS prediction for patients with STS risk scores, our local-data-driven approach reliably predicted short LOS for cardiac surgery types that do not allow STS risk calculation. We advocate that each institution with sufficient observational data should build their own cardiac surgery risk models.
基金supported in part by the National Institute on Aging of National Institutes of Health(Grant AG028709)the FUMEC and AMC for funds to support the 2016 summer research yield at the University of California in San Diego
文摘Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles （NP）-embedded silica nanoshuttles （MGNSs） with nanopores on their surface. Fluorescently labeled Doxombicin （DOX）, a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P（NIPAM-co- MAA） to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in： （a） a glass capillary tube to simulate their delivery via blood vessels; and （b） porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier {BBB）. The viscoelastic properties of hydrogels were examined by atomic force microscopy （AFM）. Cellular uptake of DOX- loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells （iPSCs） as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells＇ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics＇ payloads and precisely guided transport in specified tissues and organs （for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain） for highly efficient personalized medicine applications.
