Optimal reaction coordinate as a biomarker for the dynamics of recovery from kidney transplant.

The evolution of disease or the progress of recovery of a patient is a complex process, which depends on many factors. A quantitative description of this process in real-time by a single, clinically measurable parameter (biomarker) would be helpful for early, informed and targeted treatment. Organ transplantation is an eminent case in which the evolution of the post-operative clinical condition is highly dependent on the individual case. The quality of management and monitoring of patients after kidney transplant often determines the long-term outcome of the graft. Using NMR spectra of blood samples, taken at different time points from just before to a week after surgery, we have shown that a biomarker can be found that quantitatively monitors the evolution of a clinical condition. We demonstrate that this is possible if the dynamics of the process is considered explicitly: the biomarker is defined and determined as an optimal reaction coordinate that provides a quantitatively accurate description of the stochastic recovery dynamics. The method, originally developed for the analysis of protein folding dynamics, is rigorous, robust and general, i.e., it can be applied in principle to analyze any type of biological dynamics. Such predictive biomarkers will promote improvement of long-term graft survival after renal transplantation, and have potentially unlimited applications as diagnostic tools.

Outcomes after major hepatectomy in elderly patients.

BACKGROUND: We aimed to study the early and longterm outcomes of patients 70 years and older undergoing major liver resections, and compare the results with patients below the age of 70 years. STUDY DESIGN: All patients undergoing major liver resection (defined as three segments or more) from January 1993 to June 2004 were included. Patients were studied in two groups: 70 years of age and older (group E, elderly) and less than 70 years old (group Y, young). Early outcomes and longterm survival were analyzed. RESULTS: A total of 517 patients underwent major liver resection: group E, n=127; group Y, n=390 patients. There was no difference in operative mortality (group E, 7.9%; group Y, 5.4%; p=0.32) or postoperative morbidity (p=0.22) between the groups. Overall and disease-free survivals were not notably different for all patients (59% versus 57%, p=0.89; 60% versus 55%, p=0.28, respectively) or for a subgroup of patients with colorectal liver metastases (61% versus 55%, p=0.76; 60% versus 47%, p=0.07) in groups E versus Y, respectively. In multivariable analysis, American Society of Anesthesiologists grade 3 (p=0.024, hazard ratio [HR]=1.59, versus grade 1, 95% CI=1.06 to 2.39) and intraoperative transfusion>3 U (p<0.0005, HR=2.56, 95% CI=1.84 to 3.56) were predictors for overall survival. More than three tumors (p=0.025, HR=1.41, 95% CI=1.04 to 1.90) and redo resection (p=0.001, HR=2.80, 95% CI=1.51 to 5.19) were predictors of disease-free survival. CONCLUSIONS: Major liver resections can be safely performed in patients 70 years of age or older, with early results and survival similar to those in the younger than 70 age group. American Society of Anesthesiologists grade 3 and intraoperative transfusions>3 U were predictors for overall survival, and more than three tumors and redo resection were predictors for disease-free survival.