Mesenchymal Stem Cell-Based Immunomodulation in Allogeneic Heterotopic Heart-Lung Transplantation

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model. The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment. The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D. In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation

Portal Vein Arterialization in a Patient with Acute Liver Failure

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die waiting for a transplant because of donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment (1). Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of the hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy and in toxic-inducedALFmodel(2–4). Furthermore, we have reported a case of PVA performed to rescue a dearterialized liver graft with80%hepatocyte necrosis as a bridge for retransplantation (5). Wepresent here a clinical case of ALF successfully treated with a modified PVA technique. A 25-year-old female was admitted to our hospital for abdominal pain and asthenia. Blood tests revealed severe coagulopathy and hypertransaminasemia (Table 1). Her medical history was unremarkable except for a recent administration of tetracyclines for acne. The viral or autoimmune hepatitis markers were absent. Her liver function deteriorated rapidlyandthe neurological statusworsenedto deepcomarequiring respiratory assistance within 2 days. This dramatic clinical course and the persistent delay of a donor prompted us to attempt, with the informed consent of the family, a PVA procedure by anastomosing the inferior mesenteric artery to the inferior mesenteric vein. At surgery, the liver was macroscopically necrotic and a biopsy showed a severe confluent parenchymal necrosis. In the following days, the neurological conditions improved rapidly as did the hepatic function tests. The coma resolved within 2 days and she was extubated 3 days after arterialization. Ten days later, an angiography demonstrated the shunt patency (Fig. 1 panel A) and only a mild increase in portal pressure(22mmHg).Thepatientliverfunctiontestsprogressivelyimprovedexceptfora marked cholestasis requiring several carbon hemodialysis sessions and a reduced prothrombin activity. A liver biopsy performed 22 days from PVA revealed residual small foci of lobular necrosis and mild inflammation associated, however, with severe cholestasis and collapse of the reticuline fibres. Toavoid long-term complications related to portal hypertension, the arteriovenous shunt was closed with a metal coil during an angiographic procedure (Fig. 1 panel B) leading to a normalization of the portal bloodflow.Thepatientwasdischargedfrom hospital 29 days after PVA and liver tests progressively normalized in the following months. At present, she is in good clinical conditions, back at work and liver tests are normal. Although we cannot rule out the possibility that this patient could have recovered spontaneously, this event is very rare in deeply comatose patients with non-acetaminophen-induced ALF. By bringing the portal vein oxygen saturation up to an arterial blood level, thus likely matching the increased metabolic demand of the regenerating cells, a temporary PVA procedure can represent a new tool in the multidisciplinary approach to ALF. However, clinical trials are needed to validate this positive initial experience before PVA becomes part of clinical practice

Feasibility and effectiveness of a combined individual and psychoeducational group intervention in psychiatric residential facilities: A controlled, non-randomized study

This controlled, non-randomized study explored the feasibility of introducing a Combined Individual and Group Intervention (CIGI) for users with mental disorders in residential facilities, and tested whether users who received the CIGI had better functioning than users who received the Treatment-As-Usual (TAU), at two-year follow up. In the CIGI, a structured cognitivebehavioral approach called VADO (in English, Skills Assessment and Definition of Goals) was used to set specific goals with each user, while Falloon's psychoeducational treatment was applied with the users as a group. Thirty-one professionals attended a training course in CIGI, open to users' voluntary participation, and applied it for two years with all users living in 8 residential facilities of the Mental Health Department of Modena, Italy. In the same department, 5 other residential facilities providing TAU were used as controls. ANOVA for repeated measures showed a significant interaction effect between users' functioning at baseline and follow up assessments, and the intervention. In particular, change in global functioning was higher in the 55 CIGI users than in the 44 TAU users. These results suggest that CIGI can be successfully introduced in residential facilities and may be useful to improve functioning in users with severe mental disorders

Endolymphatic immunotherapy for advanced hepatocellular carcinoma: an update of our experience

Aim: We report an update of our experience on endolymphatic immunotherapy in patients with advanced hepatocellular carcinoma (HCC) not eligible for surgery.Methods: From 2003 to 2009 we enrolled 39 patients with advanced HCC not suitable for surgery. Patients underwent monthly endolymphatic injections of 1.5 × 106-3.0 × 106 IL-2-activated peripheral autologous lymphocytes and 250U of IL-2. Blood biochemistry every 3 months and imaging studies every 6 months were performed. Evaluation of the results was done according to clinical and pathological characters mainly including etiology, Child-Pugh class, size and number of lesions, α-fetoprotein, lymphadenopathy, vascular invasion, Response Evaluation Criteria in Solid Tumours criteria for tumour burden, biochemical parameters and survival rates.Results: Ten patients completed 12 therapy cycles, 6 received 6 infusions, 10 only 3-4 injection and 13 patients received less than 3 injections and where considered not suitable for evaluation. No clinically significant adverse reactions occurred. Imaging studies showed no significant decrease in tumour mass. Survival of treated patients was significantly higher with respect to control group (P < 0.0001). The 1-year survival was 0% in the control group vs. 50% in the treated group. In addition survival of patients who completed 12 therapy cycles appeared higher with respect to patients who underwent less than 6 cycles without reaching statistical significance due to the small number of patients. All patients with 12 completed cycles showed an improvement of 9 parameters or more.Conclusion: Endolymphatic administration of immunotherapy appeared safe, easy to perform and effective in terms of survival. This study should encourage future large scale studies in order to reach a firmer conclusion and define uniform inclusion criteria

Radical surgical treatment of recurrent hepatic hydatidosis

The treatment of relapsing hydatidosis must aim at the reduction of both morbidity and mortality rates and the risk of new recurrences

Portal blood arterialization with an extracorporeal device to treat toxic acute hepatic failure in a swine model

The role of extracoproreal device to treat acute liver failure is reported in this study

Hepatic resection for primary or secondary malignancies with involvement of the inferior vena cava: is this operation safe or hazardous?

This study evaluated surgical techniques and results of patients with tumors who had undergone liver resection with partial resection and reconstruction of the IVC

Portal vein arterialization increases liver regeneration in acute liver failure induced by extended hepatectomy or toxin administration in the rat

none11noneNardo B.; Puviani L.; Montalti R.; Beltempo P.; Bertelli R.; Pacilè V.; Licursi M.; Pertosa A.M.; Pariali M.; Caraceni P.; Cavallari A.Nardo B.; Puviani L.; Montalti R.; Beltempo P.; Bertelli R.; Pacilè V.; Licursi M.; Pertosa A.M.; Pariali M.; Caraceni P.; Cavallari A