Impact of Rabbit Antithymocyte Globulin Dose on Long-term Outcomes in Heart Transplant Patients.

BACKGROUND: Optimal dosing strategies have not been established for rabbit antithymocyte globulin (rATG) after heart transplantation, and there is currently wide variability in rATG regimens with respect to both dose and duration. METHODS: In a retrospective, single-center analysis, 523 patients undergoing heart transplantation during 1996 to 2009 were stratified by cumulative rATG dose: less than 4.5 mg/kg (group A), 4.5 to 7.5 mg/kg (group B) or greater than 7.5 mg/kg (group C). RESULTS: Survival at 1 year after transplantation was 80% in group A, 90% in group B, and 88% in group C (P = 0.062). Incidence of acute rejection per 1000 patient-years was significantly higher in group A (hazards ratio [HR], 54.8; 95% confidence interval [95% CI], 33.9-83.8) compared to groups B (19.6; 95% CI, 11.4-31.4) and C (23.6; 95% CI, 17.5-31.3). Incidence of severe infection 10 years after transplantation was higher in group C (45%) than groups A (37%) or B (23%) (P < 0.001); cytomegalovirus infection rates were 35%, 20% and 23%, respectively (P = 0.009). Multivariable Cox regression showed an HR of 0.51 (95% CI, 0.25-1.02) for acute rejection with group B versus group A, and 0.54 (95% CI, 0.33-0.88; P = 0.013) for severe infection. The rate of malignancy per 1000 patient-years was higher in groups B (13.85) and C (14.95) than group A (7.83). CONCLUSIONS: These retrospective data suggest that a cumulative rATG dose of 4.5 to 7.5 mg/kg may offer a better risk-benefit ratio than lower or higher doses, with acceptable rates of infection and posttransplant malignancy. Prospective trials are needed.

Predictive value of neuromarkers supported by a set of clinical criteria in patients with mild traumatic brain injury: S100B protein and neuron-specific enolase on trial: clinical article.

OBJECT: The role of the neuromarkers S100B protein and neuron-specific enolase (NSE) in minor head injury is well established. Moreover, there are sensitive decision rules available in the literature to identify clinically important brain lesions. However, it is not clear if using the biomarkers has an influence on the predictability of the decision rule. The purpose of this study was to determine if a set of preclinical and clinical parameters combined with 2 neuromarker levels could serve as reliable guidance for accurate diagnosis. METHODS: Prospective evaluation of a cohort of head trauma patients with Glasgow Coma Scale scores of 13-15 was performed at an academic, Level I trauma center. Blood samples and cranial CT studies were obtained for all patients within 3 hours after injury. The hypothesis of the study was whether the combination of an increase of S100B and NSE levels in serum and other defined risk factors are associated with a pathological finding on CT. A forward stepwise logistic regression model was used. RESULTS: The study included 107 head trauma patients with a mean age of 59 ± 23 years. Twenty-five patients (23.4%) had traumatic lesions on CT. Eight patients underwent craniotomy. The analysis provided a model with good overall accuracy for discriminating cases with clinically important brain injury, including the 6 variables of S100B, NSE, nausea, amnesia, vomiting, and loss of consciousness. The area under the curve (AUC) was 0.88 (0.83-0.93). The receiver operating characteristic curve plots detecting clinically important brain injury for the single variables of S100B and NSE showed an AUC of 0.63 and 0.64, respectively. Conclusions The integration of the neuromarker panel as part of a diagnostic rule including the high-risk factors of nausea, vomiting, amnesia, and loss of consciousness is safe and reliable in determining a diagnosis, pending the availability of more brain-specific neuromarkers. CLINICAL TRIAL REGISTRATION NO.: NCT00622778 (ClinicalTrials.gov).