Background-The Model for End-Stage Liver Disease (MELD) predicts events in cirrhotic subjects undergoing major surgery and may offer similar prognostication in left ventricular assist device candidates with comparable degrees of multisystem dysfunction. Methods and Results-Preoperative MELD scores were calculated for subjects enrolled in the University of Michigan Health System (UMHS) mechanical circulatory support database. Univariate and multiple regression analyses were performed to investigate the ability of patient characteristics, laboratory data (including MELD scores), and hemodynamic measurements to predict total perioperative blood product exposure and operative mortality. The ability of preoperative MELD scores to predict operative mortality was evaluated in subjects enrolled in the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), and results were compared with those from the UMHS cohort. The meanϮSD MELD scores for the UMHS (nϭ211) and INTERMACS (nϭ324) cohorts were 13.7Ϯ6.1 and 15.2Ϯ5.8, respectively, with 29 (14%) and 19 (6%) perioperative deaths. In the UMHS cohort, median total perioperative blood product exposure was 74 units (25th and 75th percentiles, 44 and 120 units). Each 5-unit MELD score increase was associated with 15.1Ϯ3.8 units (␤ϮSE) of total perioperative blood product exposure. Each 10-unit increase in total perioperative blood product exposure increased the odds of operative death (odds ratio, 1.05; 95% confidence interval, 1.01 to 1.10). Odds ratios, measuring the ability of MELD scores to predict perioperative mortality, were 1.5 (95% confidence interval, 1.1 to 2.0) and 1.5 (95% confidence interval, 1.1 to 2.1) per 5 MELD units for the UMHS and INTERMACS cohorts, respectively. When MELD scores were dichotomized as Ն17 and Ͻ17, risk-adjusted Cox proportional-hazard ratios for 6-month mortality were 2.5 (95% confidence interval, 1.2 to 5.3) and 2.5 (95% confidence interval, 1.1 to 5.4) for the UMHS and INTERMACS cohorts, respectively. Conclusion-The MELD score identified left ventricular assist device candidates at high risk for perioperative bleeding and mortality. (Circulation. 2010;121:214-220.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron cell death in the cortex, brainstem, and spinal cord. Extensive efforts have been made to develop trophic factor-based therapies to enhance motor neuron survival; however, achievement of adequate therapeutic delivery to all regions of the corticospinal tract has remained a significant challenge. Here, we show that adeno-associated virus serotype 4 (AAV4)-mediated expression of insulin-like growth factor-1 (IGF-1) or vascular endothelial growth factor (VEGF)-165 in the cellular components of the ventricular system including the ependymal cell layer, choroid plexus [the primary cerebrospinal fluid (CSF)-producing cells of the central nervous system (CNS)] and spinal cord central canal leads to trophic factor delivery throughout the CNS, delayed motor decline and a significant extension of survival in SOD1(G93A) transgenic mice. Interestingly, when IGF-1- and VEGF-165-expressing AAV4 vectors were given in combination, no additional benefit in efficacy was observed suggesting that these trophic factors are acting on similar signaling pathways to modestly slow disease progression. Consistent with these findings, experiments conducted in a recently described in vitro cell culture model of ALS led to a similar result, with both IGF-1 and VEGF-165 providing significant motor neuron protection but in a nonadditive fashion. These findings support the continued investigation of trophic factor-based therapies that target the CNS as a potential treatment of ALS.

Background Mechanical circulatory support (MCS) with temporary, extracorporeal assist devices restores hemodynamics in patients with refractory cardiogenic shock. These devices are frequently used in community hospitals, with subsequent referral to tertiary care centers. We sought to determine the outcomes of such referrals and identify prognostic variables that may influence management decisions. Methods We performed a single-institution retrospective review of 59 consecutive patients transferred on temporary, extracorporeal MCS from 1997 to 2008. Demographics, medical history, laboratory data, and clinical status were obtained, with survival determined from the medical record and the Social Security Death Index. Univariable and multivariable analysis were performed and survival estimates were determined using the Kaplan-Meier method. Results Median age was 49.6 years (range, 14 to 77 years). Forty-five patients (76%) were supported for postcardiotomy failure, and 34 (58%) required biventricular support. Twenty-five (42%) survived to hospital discharge, 11 after cardiac recovery (44%), 9 with long-term implantable MCS devices (39%), and 5 after heart transplantation (22%). Eight patients discharged with implantable MCS devices underwent heart transplantation and 1 remains alive on long-term implantable MCS support. Survival was 42% ± 6% at 1 year and 38% ± 6% at 5 years. Age and renal function were independent predictors of death. Conclusions Nearly half of all patients transferred on temporary extracorporeal MCS survive to discharge. Most of the long-term survivors received a heart transplant. Age and renal function were independent predictors of death, suggesting that survival is maximized by considering eligibility for cardiac transplantation.

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