Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications after radical cystectomy.

OBJECTIVE: To investigate whether poor preoperative cardiopulmonary reserve and comorbid state dictate high-risk status and can predict complications in patients undergoing radical cystectomy (RC). PATIENTS AND METHODS: In all, 105 consecutive patients with transitional cell carcinoma (TCC; stage T1-T3) undergoing robot-assisted (38 patients) or open (67) RC in a single UK centre underwent preoperative cardiopulmonary exercise testing (CPET). Prospective primary outcome variables were all-cause complications and postoperative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all-cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman's rank correlation and group comparison, the Mann-Whitney U-test and Fisher's exact test. Any relationships were confirmed using the Mantel-Haenszel common odds ratio estimate, Kaplan-Meier analysis and the chi-squared test. RESULTS: The anaerobic threshold (AT) was negatively (r = -206, P = 0.035), and the ventilatory equivalent for carbon dioxide (VE/VCO2) positively (r = 0.324, P = 0.001) correlated with complications and LOS. Logistic regression analysis identified low AT (<11 mL/kg/min), high VE/VC02 (≥33) and hypertension as significant factors, such that, in their presence patients were 5.55-times more likely to have complications at 90 days postoperatively [P = 0.001, 95% confidence interval (CI) 2.2-13.9]. ROC analysis showed a high significance (area under the curve 0.78, 95% CI 0.69-0.87; P < 0.001). In addition, based on CPET criteria >50% of patients presenting for RC had significant heart failure, whereas preoperatively only very few (2%) had this diagnosis. Analysis using the Mann-Whitney test showed that a VE/VCO2 ≥33 was the most significant determinant of LOS (P = 0.004). Kaplan-Meier analysis showed that patients in this group had an additional median LOS of 4 days (P = 0.008). Finally, patients with an American Society of Anesthesiologists grade of 3 (ASA 3) and those on long-term ß-blocker therapy were found to be at particular risk of myocardial infarction (MI) and death after RC with odds ratios of 4.0 (95% CI 1.05-15.2; P = 0.042) and 6.3 (95% CI 1.60-24.8; P = 0.008). CONCLUSION: Patients with poor cardiopulmonary reserve and hypertension are at higher risk of postoperative complications and have increased LOS after RC. Heart failure is known to be a significant determinant of perioperative death and is significantly under diagnosed in this patient group.

Characterising recovery from renal transplantation and live-related donation using cardiopulmonary exercise testing.

BACKGROUND: An association between end-stage renal failure and exercise intolerance exists. Whether live kidney donation impacts on exercise tolerance is unknown. Here recovery post renal transplant and donation using cardiopulmonary exercise testing is investigated. METHODS: Renal donors (n = 28) and recipients (n = 24) undertook a cardiopulmonary exercise test, Duke activity score index and patient reported health score questionnaires pre-operatively and in the 7th and 14th week post-operatively. Anaerobic threshold, peak oxygen uptake and ventilatory equivalents were measured in relation to activity and reported health scores. Haemoglobin and renal function was recorded. RESULTS: Recipients showed impaired cardiopulmonary function compared to donors with lower anaerobic threshold (10.5 vs. 14.4 ml/kg/min) and peak oxygen uptake (18.5 vs 23.0 ml/kg/min). Post-operatively the anaerobic threshold of recipients improved and normalised by the 14th week, whereas that in donors fell by ∼20% by the 7th (mean 11.4 ml/kg/min), recovering by the 14th (mean 15.6 ml/kg/min). Reported health but not activity scores showed similar changes. CONCLUSIONS: Recovery following renal transplantation and donation differ. Transplantation improves renal function resulting in an increase in anaerobic threshold and peak oxygen uptake which essentially normalise by the 14th week post-operatively. Donors suffer a 20% reduction in cardiopulmonary reserve post-operatively, which recovers by the 14th week, suggesting no associated chronic exercise intolerance.IMPLICATIONS FOR REHABILITATIONCardiopulmonary exercise testing is a real-time predictor of functional capacity and thus is used as a pre-operative tool to measure physiological fitness and predict outcomes.Renal failure is associated with exercise intolerance and transplantation is transformational in terms of quality of life, longevity and healthcare cost.Live - related renal donation is increasingly available but whether donation itself carries a long-term health burden has not been previously well established.This study suggests that renal donation is not associated with long-term cardiopulmonary compromise and patients who donate their kidneys recover their previous fitness within 14 weeks.

A bioluminescent microbial biosensor for in vitro pretreatment assessment of cytarabine efficacy in leukemia.

BACKGROUND: The nucleoside analog cytarabine (Ara-C [cytosine arabinoside]) is the key agent for treating acute myeloid leukemia (AML); however, up to 30% of patients fail to respond to treatment. Screening of patient blood samples to determine drug response before commencement of treatment is needed. This project aimed to construct and evaluate a self-bioluminescent reporter strain of Escherichia coli for use as an Ara-C biosensor and to design an in vitro assay to predict Ara-C response in clinical samples. METHODS: We used transposition mutagenesis to create a cytidine deaminase (cdd)-deficient mutant of E. coli MG1655 that responded to Ara-C. The strain was transformed with the luxCDABE operon and used as a whole-cell biosensor for development an 8-h assay to determine Ara-C uptake and phosphorylation by leukemic cells. RESULTS: Intracellular concentrations of 0.025 µmol/L phosphorylated Ara-C were detected by significantly increased light output (P < 0.05) from the bacterial biosensor. Results using AML cell lines with known response to Ara-C showed close correlation between the 8-h assay and a 3-day cytotoxicity test for Ara-C cell killing. In retrospective tests with 24 clinical samples of bone marrow or peripheral blood, the biosensor-based assay predicted leukemic cell response to Ara-C within 8 h. CONCLUSIONS: The biosensor-based assay may offer a predictor for evaluating the sensitivity of leukemic cells to Ara-C before patients undergo chemotherapy and allow customized treatment of drug-sensitive patients with reduced Ara-C dose levels. The 8-h assay monitors intracellular Ara-CTP (cytosine arabinoside triphosphate) levels and, if fully validated, may be suitable for use in clinical settings.