Prehabilitation for the Frailty Syndrome: Improving Outcomes for Our Most Vulnerable Patients.

Anesthetists are increasingly faced with the challenge of delivering perioperative care to frail older people. Patients with frailty undergoing surgical intervention are at a significantly increased risk of perioperative complications, mortality, and longer length of stay. Moreover, frailty is often associated with multimorbidity and a range of geriatric syndromes including functional dependency, cognitive impairment, and malnutrition which further increases risk and complexity of care. There is a growing body of evidence that prehabilitation-intervention delivered during the preoperative period to improve overall health and function-can improve postoperative outcomes for patients undergoing surgery. However, whether this vulnerable population stand to benefit from prehabilitation is less clear. We review the evidence for prehabilitation for patients with frailty including whether the risks associated with and outcomes from surgery can be modified through comprehensive geriatric assessment.

The Prognostic Performance of Frailty for Delirium and Functional Decline in Vascular Surgery Patients.

BACKGROUND: Frailty in older vascular surgery patients is associated with increased mortality, hospital stay, and morbidity. The association of frailty with hospital-acquired geriatric syndromes such as delirium and functional decline has not been well studied. OBJECTIVES: To investigate the association between frailty and hospital-acquired geriatric syndromes in older hospitalized vascular surgery patients, and to evaluate the prognostic performance of the frailty index (FI) and the Clinical Frailty Scale (CFS) for delirium and functional decline. DESIGN: Prospective cohort study. SETTING: Acute care academic hospital. PARTICIPANTS: Patients aged 65 years or more admitted to a tertiary vascular surgery unit (N=150). MEASUREMENTS: Frailty was assessed using the FI and CFS. The adjusted association of frailty status with delirium and functional decline was assessed using logistic regression analysis. The prognostic performance of FI and CFS was determined by assessing C-statistic and positive and negative predictive values (PPV and NPV). RESULTS: Of 150 participants, FI identified 34 (23%) and CFS identified 45 (30%) as frail. Frailty was an independent predictor of delirium (FI adjusted odds ratio, odds ratio (OR) = 5.66, 95% confidence interval (CI) = 1.53-21.03; CFS adjusted OR = 4.07, 95% CI = 1.14-14.50), but not functional decline. FI and CFS showed acceptable prognostic performance for delirium (C-statistic 0.74), but not functional decline (C-statistic 0.63-0.64). For both outcomes, the FI and CFS had high NPV (86-96%), and low PPV (22-29%). CONCLUSION: Frail older vascular surgery patients are more likely to develop hospital-acquired geriatric syndromes. The FI and CFS have acceptable prognostic performance for predicting delirium but not all individuals who are identified as frail develop delirium. Ongoing research is needed to identify interventions that improve outcomes in patients who screen positive for frailty.

Impact of tumor cell VEGF expression on the in vivo efficacy of vandetanib (ZACTIMA; ZD6474).

UNLABELLED: VEGF is the key player in tumor angiogenesis. In the current study, the impact of VEGF expression on the response of tumors to the VEGFR2 associated tyrosine kinase inhibitor vandetanib was evaluated. MATERIALS AND METHODS: Human colon carcinoma (HT29) and murine squamous carcinoma (SCCVII) clonal cell lines expressing varying levels of VEGF were established and their response to vandetanib was assessed in tissue culture and as solid tumors. RESULTS: Vandetanib treatment had no effect on tumor cell clonogenic cell survival in vitro but doses >or=10 nM significantly reduced endothelial cell migration. In vivo, tumors derived from cell clones expressing high levels of VEGF displayed significantly enhanced angiogenesis and more aggressive growth. An intradermal angiogenesis assay was used to demonstrate that a 4-day treatment with vandetanib (50 mg/kg/day) was able to significantly inhibit blood vessel growth induced by both parental and high VEGF-expressing tumor cell clones. In the HT29 tumor model, treatment response to vandetanib (50 mg/kg/day, Monday-Friday for 2 weeks) was greatest in xenografts derived from the highest VEGF-expressing cell clones. A similar trend was noted in the SCCVII tumor model. The present findings indicate that vandetanib therapy effectively counteracted the aggressive feature of tumor growth resulting from VEGF over-expressing tumor cells and suggest that such tumors may be particularly well suited for anti-VEGF interventions.

Impact of VEGF expression on the physiological characteristics of clonal cell lines.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis and growth in most solid neoplasia. MATERIALS AND METHODS: Clonal tumor cell lines expressing varying levels of this pro-angiogenic factor were created via recombinant adeno-associated virus infection of a human (HT29) and rodent (SCCVII) tumor model. RESULTS: The alteration in VEGF expression levels did not significantly impact the in vitro growth rate of the clonal cell lines or the expression levels of other known pro-angiogenic factors. However, the tumors that arose from these clonal cell lines did display significant physiological differences. Upregulation of VEGF expression increased the in vivo growth rate and the intratumoral vessel density of the resulting tumors and decreased the extent of tumor necrosis. CONCLUSION: Since the tumor vascular network can impact the efficacy of anti-cancer therapies, these results suggest that VEGF expression may be important to consider in the treatment of cancer.