No abstract

SummaryThe aim of this study was to identify potential risk factors linked to neurologic events (NE) occurring after liver transplantation (LT) and use them to construct a model to predict such events. From odds ratios (OR) of risk factors, a scoring system was assessed using multivariate regression analysis. Forty-one of 307 LT patients presented NE (13.3%), with prolonged hospital stay and decreased post-LT survival. On multivariate analysis, factors associated with NE included: severe pre-LT ascites OR 3.9 (1.80-8.41; P = 0.001), delta sodium ≥12 mEq/l OR 3.5 (1.36-8.67; P = 0.01), and post-LT hypomagnesemia OR 2.9 (1.37-5.98; P = 0.005). Points were assigned depending on ORs as follows: ascites 4 points, and hypomagnesemia and delta sodium ≥12 mEq/l, 3 points each (score range = 0-10 points). ROC curve analysis suggested good discriminative power for the model, with a c-statistic of 0.72 (CI 0.62-0.81; P < 0.0001), best performance for a cutoff value >3 points (71% sensitivity, 60% specificity). NE risk increased progressively from 6.4%, to 10.3%, 12.8%, 31.5% and 71.0% as scores rose from 0 to 3, 4, 6-7 and 10 cumulative points, respectively. The score described helps to identify patients potentially at risk for neurologic events, and its prevention would decrease morbidity and mortality after LT.

We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated the effects of LMW HA priming on human-tumor-pulsed monocytes-derived dendritic cells (DC/TL) obtained from healthy donors and patients with CRC. LMW HA treatment resulted in an improved maturation state of DC/TL and an enhanced mixed leucocyte reaction activity in vivo. Importantly, pre-conditioning of DC/TL with LMW HA increased their ability to migrate and reduced their attraction to human tumor derived supernatants. These effects were associated with increased CCR7 expression levels in DC. Indeed, a significant increase in migratory response toward CCL21 was observed in LMW HA primed tumor-pulsed monocyte-derived dendritic cells (DC/TL/LMW HA) when compared to LWM HA untreated cells (DC/TL). Moreover, LMW HA priming modulated other mechanisms implicated in DC migration toward lymph nodes such as the metalloproteinase activity. Furthermore, it also resulted in a significant reduction in DC migratory capacity toward tumor supernatant and IL8 in vitro. Consistently, LMW HA dramatically enhanced in vivo DC recruitment to tumor-regional lymph nodes and reduced DC migration toward tumor tissue. This study shows that LMW HA –a poorly immunogenic molecule- represents a promising candidate to improve human DC maturation protocols in the context of DC-based vaccines development, due to its ability to enhance their immunogenic properties as well as their migratory capacity toward lymph nodes instead of tumors.

Controversy exists whether NE after LT are more frequently observed in children or adults. We aimed to compare the incidence and outcomes for NE after LT in pediatric and adult recipients. A single-center cohort study, including all LT between 2001 and 2013, was performed. Definition of NE included impaired consciousness, delirium, seizures, focal neurologic deficit, visual impairment, or slurred speech. A cohort of 443 consecutive LT recipients was included: 307 adults and 136 children. Cumulative incidence of NE was similar between adults 15% (n = 41) and children 16% (n = 20; P = .73) with a complete neurological recovery in 62% and 95% of the patients, respectively (P < .0001). Adults with NE had significantly lower survival (70% vs 76%; P = .015) with a HR of 2.36; this was similarly observed in children (45% vs 66%; HR 2.05, CI 0.66; 6.34). Independent risk factors for NE in adults were pre-LT ascites, delta sodium, and post-LT hypomagnesemia, whereas in children pre-LT encephalopathy ≥II and serum albumin were associated with NE. Although a similar incidence of NE after LT was observed, children were more likely to achieve neurological recovery. Risk factors for the development of NE are difficult to assess in both populations.