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Liver transplantation corrects the metabolic unbalance in a child with lathosterolosis (OMIM #607330) and favors amelioration of her neurodevelopmental delay.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult’s hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuoventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Donor–recipient match is a matter of debate in liver transplantation. D‐MELD (donor age × recipient biochemical model for end‐stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3‐year patient survival. D‐MELD cutoff predictive of 5‐year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (). Differences among D‐MELD deciles allowed their regrouping into three D‐MELD classes (A < 338, B 338–1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44–2.85) in D‐MELD class C versus B. The OR was 0.40 (95% CI, 0.24–0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11–1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51–0.93), retransplant (OR = 1.82; 95% CI, 1.16–2.87) and low‐volume center (OR = 1.48; 95% CI, 1.11–1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59–2.43) for D‐MELD class C versus class B and 0.42 (95% CI, 0.29–0.60) for D‐MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D‐MELD ≥ 1750). The innovative approach offered by D‐MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Donor–recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338–1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44–2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24–0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11–1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51–0.93), retransplant (OR = 1.82; 95% CI, 1.16–2.87) and low-volume center (OR = 1.48; 95% CI, 1.11–1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59–2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29–0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

The aim of the study was to evaluate safety and efficacy of IP in LT, particularly in marginal grafts. From 2007 to 2008, 75 LT donors were randomized to receive IP (IP+) or not (IP−). Considering the graft quality, we divided the main groups in two subgroups (marg+/marg−). IP was performed by 10-min inflow occlusion (Pringle maneuver utilizing a toruniquet). Donor variables considered were gender, age, AST/ALT, ischemia time and steatosis. Recipient variables were gender, age, indication to LT and MELD/CHILD/UNOS score. AST/ALT levels, INR, bilirubin, lactic acid, bile output on postoperative days 1, 3 and 7 were evaluated. Histological analysis was performed evaluating necrosis/steatosis, hepatocyte swelling, PMN infiltration and councilman bodies. Thirty patients received IP+ liver. No differences were seen between groups considering recipient and donor variables. Liver function and AST/ALT levels showed no significant differences between the main two groups. Marginal IP+ showed lower AST levels on day1 compared with untreated marginal livers (936.35 vs. 1268.23; p = 0.026). IP+ livers showed a significant reduction of moderate-severe hepatocyte swelling (33.3 % vs. 65.9 % ; p = 0.043). IP+ patients had a significant reduction of positive early microbiological investigations (36.7 % vs. 57.1 % ; p = 0.042). In our experience IP was safe also in marginal donors, showing a protective role against IRI.

The aim of the study was to evaluate safety and efficacy of IP in LT, particularly in marginal grafts. From 2007 to 2008, 75 LT donors were randomized to receive IP (IP) or not (IP-). Considering the graft quality, we divided the main groups in two subgroups (margmarg-). IP was performed by 10-min inflow occlusion (Pringle maneuver utilizing a toruniquet). Donor variables considered were gender, age, ASTALT, ischemia time and steatosis. Recipient variables were gender, age, indication to LT and MELDCHILDUNOS score. ASTALT levels, INR, bilirubin, lactic acid, bile output on postoperative days 1, 3 and 7 were evaluated. Histological analysis was performed evaluating necrosissteatosis, hepatocyte swelling, PMN infiltration and councilman bodies. Thirty patients received IP liver. No differences were seen between groups considering recipient and donor variables. Liver function and ASTALT levels showed no significant differences between the main two groups. Marginal IP showed lower AST levels on day1 compared with untreated marginal livers (936.35 vs. 1268.23; p 0.026). IP livers showed a significant reduction of moderate-severe hepatocyte swelling (33.3 vs. 65.9; p 0.043). IP patients had a significant reduction of positive early microbiological investigations (36.7 vs. 57.1; p 0.042). In our experience IP was safe also in marginal donors, showing a protective role against IRI.

Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitroand in vivoafter subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angionesis-related factors VEGF, αVβ3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation.

Background: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. Methods: We analysed data from 34@?664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21@?605 in training dataset) and 12-months (n=18@?852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). Findings: 2540 of 21@?605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. Increased mortality at 3-months post-transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant centre (>=70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. Interpretation: The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centres. Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups.

Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation (LT). Graft and patient survival are adversely affected by recurrent infection of the graft. Recent publications have described an inferior outcome for recently transplanted HCV patients and have highlighted the impact of advancing donor age on severity of recurrent HCV. The donor age at which a measurable impact on graft and patient outcome can be observed has not clearly been defined. In addition, the impact of donor age on graft and patient survival for non-HCV patients needs to be examined.

We discuss the scalar propagator on generic ADSd+1 × S^d'+1 backgrounds. For the conformally flat situations and masses corresponding to Weyl invariant actions the propagator is powerlike in the sum of the chordal distances with respect to AdSd+1 and S^d'+1. In all other cases the propagator depends on both chordal distances separately. We discuss the KK mode summation to construct the propagator in brief. For AdS5 × S⁵ we relate our propagator to the expression in the BMN plane wave limit and find a geometric interpretation of the variables occurring in the known explicit construction on the plane wave.

We construct a set of tachyonic lumps in Vacuum String Field Theory that, in the presence of a background B field, give in the low energy limit exactly the complete sequence of noncommutative GMS solitons.

Background: The role of excessive duodenogastric reflux (DRG) in the genesis of gastric symptoms in patients primarily referred for both gastroesophageal reflux (GER) symptoms and esophagitis is poorly understood. Methods: The study is based on the clinical, endoscopic, histologic, and 24-hour gastric data from the Bilitec optoelectronic device (Prodotec, Florence, Italy, licensed by Synectics Medical, Stockholm, Sweden) from 49 patients having both typical GER symptoms and gastric symptoms suggestive of excessive DGR (ie, epigastric pain, nausea, or bilious vomiting) in the absence of previous esophageal or gastric surgery (group I). Helicobacter pylori organisms were searched for on antral biopsy specimens with use of the Giemsa method. The percentages of total, upright, and supine time during which absorbance exceeded various thresholds through all the working range of the Bilitec device were calculated. Bilitec data from group 1 were compared with those from 16 patients with endoscopic esophagitis and GER symptoms only (group 2) and 25 healthy subjects (group 3). Results: The prevalence of an abnormal Bilitec test result in group 1 increased from 27% (13/49) at the 0.25 absorbance threshold to 36% (18/49) at thresholds ranging from 0.40 to 0.60 and to 41% (20/49) when multiple thresholds ranging from 0.25 to 0.60 were considered. In group 2 one patient had an abnormal Bilitec test result at the 0.25 to 0.30 threshold, whereas the other 15 patients had a normal test result. H pylori antral infection was present in 14 group 1 patients. None of these had an abnormal Bilitec test result, whereas the test was positive in 40% of the H pylori-negative patients without endoscopic gastritis and in 70% of H pylori-negative patients with endoscopic gastritis (P = .001). Conclusions: Twenty-four-hour intragastric bile monitoring provides the clinician with unequivocal evidence of excessive DGR in 41% of patients with an intact stomach having endoscopic esophagitis, GER symptoms, and gastric symptoms suggestive of DGR. The most dependable data are obtained when absorbance thresholds higher than 0.40 are considered. H pylori antral infection and excessive DGR at 24-hour intragastric bile monitoring are mutually exclusive. (Surgery 1999;125:480-6.)

Fifty-nine orthotopic liver transplant (OLT) patients were studied after transplantation to detect Epstein-Barr virus (EBV) primoinfection and reactivation. Nineteen, all children under 10 years, were EBV seronegative. Seroconversion occurred in 12 (63.3%) of the seronegative patients. Most of these patients (10/12) seroconverted 2 or 3 months after transplantation; 11 out of the 12 demonstrated clinical signs at the time of seroconversion. From 9 primoinfected patients tested for EBV excretion, 8 were found to be positive. Serological evidence of reactivation was found in 9 out 40 (22.5%) seropositive patients and EBV was isolated from 5 (56%). Eleven pediatrie OLT patients with primoinfection showed high and persistent titers of anti-EA antibodies (from 1:32 to > 1:256), when tested at least 3 months after serovonversion; however, anti-EBNA antibodies failed to develop in 5 patients and remained persistently low in 4. These patients with high EA and with negative or low EBNA titers constitute an “at risk” group for EBV-related lymphoproliferative syndrome (LpS). At presently, after a period of follow-up ranging from 3 months to 3 years, none of our 12 primoinfected patients have developed any lymphoproliferative evolution. However, in 1, during the acute phase, lymphoblasts and lymphoproliferation were observed in a tonsil biopsy.

Summary: OKT3 is a monoclonal antibody used as T-specific immunosuppressor agent in the treatment of acute rejection of hepato- or renal-transplanted patients. The immunosuppressor effect is related to the elimination and modulation of T-cells after the binding between OKT3 and the specific antigen CD3+. This drug has been used in the treatment of acute rejection. The more frequent side effects is the immunogenic reaction Human Antibody Mouse Antibody (HAMA). The aim of this study is the evaluation of the dose and the administration route of the OKT3. The results of the antibody monitoring in the plasma of the treated patients and the analysis of the clinical data were evaluated to focus a valid therapeutic protocol as well as a more rational time sampling of the circulating drug to achieve a correct monitoring. The results show a gradual increase of the hematic concentration of the drug, positively correlating the clinical data of hepatic biopsy and lymphocytic screening. These results have permitted to modify the therapeutic protocol previously performed. It has been defined the administration route chosing i.v. infusion (5 mg/die/2h), moreover it the therapy has been shortened to 6 days. The HAMA were also evaluated and the analysis of the data showed a negative results, suggesting the possibility of the OKT3 retreatment in the cases of rescue.