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Background Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. Materials and Methods We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. Results CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). Conclusion Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

Alcoholic hepatitis (AH) is an acute-on-chronic inflammatory response affecting the liver. It has been recognized that white blood cells (WBCs) are involved in the pathogenesis and in the prognosis of AH. The aim of study was to use Adacolumn, which can selectively adsorb myeloid linage leucocytes (granulocytes and monocytes/macrophages) from the blood in the column and improve the clinical status of patients.Six patients with a diagnosis of AH were treated with Adacolumn granulocyte-apheresis therapy.patients not responders to corticosteroids therapy with Maddrey Discriminant Function (MDF)32 and MELD score 20-26. The patients underwent five 1-hour sessions for 5 consecutive days with a follow-up at 28 days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. Liver parameters, WBC count, proinflammatory cytokines, coagulation, and predictive scores were valued before and after the cycle of apheresis treatment.After 5 days, the findings showed a significant improvement of WBC count (P .014) and cytokines such as interleukin (IL)-6 (P .019), tumor necrosis factor α (TNFα) (P .02), and IL-8 (P .029). The results probably determined a reduction of aspartate transaminase (AST; P .02) and alanine transaminase (ALT; P .011), although we did not observe a significant improve in bilirubin, prothrombin time (PT), and Maddrey score. The improvement of MELD score, depending on an improvement of international normalized ratio for administration of plasma, was not considered. At day 28 of follow-up, PT, IL-6, TNFα, AST and ALT results significantly improved.The Adacolumn apheresis was safe and was able to determine an improvement of clinical status of patients with reduction of inflammatory markers. More patients are needed to validate these results.

The Alstrom syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alstrom syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease can occur as early as the late teens and is the leading cause of death. More than 900 people with Alstrom syndrome have been reported worldwide. We present a case of a 42-year-old man affected by this syndrome with end-stage renal disease, type 2 diabetes mellitus, and loss of visual function and hearing who received a kidney transplant from a cadaveric donor. Basiliximab and steroid were used as induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as maintenance therapy. No complications were reported during the recovery. In selected patients affected by Alstrom syndrome, renal transplantation can be a successful treatment for chronic kidney disease.

Numerous evidence has been reported to support a safe 1:1 conversion from the twice-daily tacrolimus (Tac-T) to the once-daily tacrolimus regimen (Tac-O), but frequently there is a reduction in drug trough levels, which has been estimated by some authors to be about 20%. The relationship between Tac-O dosage and trough levels after conversion is not clear. The tacrolimus trough levels-to-dose ratio has been applied to better define the wide variability in doses and blood levels of tacrolimus. The aim of this study was to evaluate tacrolimus trough levels, tacrolimus daily dosage, and tacrolimus level-to-dose ratio during 1 year pre-postconversion follow-up in 31 stable kidney transplant patients who had received Tac-T therapy for over 6 months with stable renal function. They were converted to the same dosage of Tac-O. Patients before and after conversion were their own controls. The trough levels of tacrolimus showed a slight albeit significant reduction after conversion, remaining in the therapeutic range. Nineteen percent underwent an adjustment in total daily dosage after conversion versus 39% before conversion with no significant difference. No significant differences were detected in the total daily dose administered either by tacrolimus level-to-dose ratio before or after conversion. Kidney transplant recipients under Tac-O therapy were safely maintained using the same therapeutic monitoring as when receiving Tac-T.

We evaluated the possibility of preventing the evolution of endotoxin-mediated sepsis in severe septic shock using early treatment of critical endotoxemia with polymyxin-B direct hemoperfusion (PMX-DHP). Thirty-eight postsurgical patients who fulfilled at least 2 criteria for systemic inflammatory response syndrome were stratified on the basis of the value of the endotoxin activity assay. Seventeen patients who demonstrated high risk of endotoxin activity (>or=0.6) received standard therapy plus PMX-DHP every 24 hours to lower the endotoxin activity level to less than 0.4, and the remaining 21 patients with endotoxin activity levels less than 0.6 received standard therapy only. Seven patients required 2 courses of PMX-DHP therapy, 8 required 3 courses, and 2 required 4 courses. After treatment, mean arterial pressure increased, from 69.00 mm Hg to 81.35 mm Hg (P < .01); heart rate decreased, from 105.40 bpm to 78.12 bpm (P < .01); white blood cell count decreased, from 20,700 cells/mm(3) to 9740 cells/mm(3) (P < .01); arterial oxygen tension-fraction of inspired oxygen ratio increased, from 273.82 to 305.82 (P < .01); and Sequential Organ Failure Assessment score decreased, from 7 to 4 (P < .01). Length of stay was longer for transplant recipients (16 days) than for other surgical patients (8(1/2) days). All patients survived to 28-day follow-up, and 15 of 16 patients (94%) had survived at 60-day follow-up. Despite the small number of patients included in the study, the encouraging results suggest that PMX-DHP is a useful therapeutic strategy for lowering sepsis-related mortality.

Use of expanded criteria donors (ECD) has increased worldwide in previous years because of the donor scarcity. However, ECD are related to a greater risk of complications and shorter graft longevity. Delayed graft function (DGF) which impacts renal graft survival, represents one of the most common complications posttransplantation. The purpose of this study was to analyse DGF incidence among ECD kidneys and its role on early and intermediate recipient and graft survivals. We prospectively analyzed 46 ECD cases divided as group A (absence of DGF; n = 23) and B (DGF; n = 23). Group B was composed of older donors (P = .033) with longer cold ischemia times (P = .017), and greater incidences of acute rejection episodes (ARE) (P < .0001). Comparing group A with group B, we observed 1-year and 3-year overall recipient survivals to be 95.7% and 95.7% versus 91.3% and 91.3%, respectively (P = not significant). Censored 1-year and 3-year overall graft survivals were 100% and 92.9% versus 85.6% and 79.9%, respectively (P = .026). Analyzing the patients with DGF without (n = 9) versus with concomitant ARE (n = 14), no differences were noted in recipient and graft survivals. The incidence of DGF was strictly related to increased donor age, greater cold ischemia time, and presence of an ARE while DGF did not have a role in recipient survival, it reduced, graft survival. Concomitant ARE was not related to an impaired graft function.

Introduction Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis. Methods A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012. Results The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%). Conclusions Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis.

Introduction Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction. Material and Methods This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications. Results Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A. Conclusions In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results.

Introduction An urgent lung transplantation national program in Italy was developed over the past three years. Indispensable conditions that were included in the program were invasive respiratory support and/or extracorporeal vascular device (DECAP excluded). The aim of this study was to test the effectiveness of the program. Materials and Methods We analyzed urgent lung requests received between 2009 and 2011 taking into account primary pathology, request outcome, average waiting time, and organ origin. Taking as reference the same period of time, we also examined the ordinary waiting list, waiting list mortality, and number of transplantations performed and we have compared them with another three-year period prior to the activation of the program. Results The total number of urgent requests was 43. Primary pathologies with the highest incidence proportion were cystic fibrosis (40%) and idiopathic pulmonary fibrosis (26.6%). A total of 34 requests (79%) were successfully dealt with and 9 of them were suspended because of worsening conditions. The average waiting time was 17.9 days. During the same period of time 340 lung transplantations were performed and there were 499, 524, and 564 wait-listed patients in 2009, 2010, and 2011, respectively. The mortality rate was 21.3%. Over the previous three-year period 295 transplantations were performed and there were 457, 476, and 464 wait-listed patients in 2006, 2007, and 2008, respectively. Also the mortality rate was 25.3%. Discussion Urgent lung transplantations can provide patients in an imminent life-threatening situation with adequate care without affecting the mortality rate of patients on the ordinary waiting list.

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.

Background Recently, the role of antibodies has been documented in the development of acute rejection episodes. Antibody-mediated acute rejection (AMAR) may develop at any time after transplantation, with an incidence of almost 7%. Several therapeutic approaches have been proposed in the past decades. However, no data exist regarding combined plasma treatment (PT) and extracorporeal photopheresis (ECP). The aim of this study was to report an initial single-center experience of combined PT and ECP with high-dose intravenous immunoglobulin (IVIg) for the treatment of AMAR. Methods Three patients were treated with this approach. Results In 2 cases, we observed immediate restoration of graft function, and in 1 case, in which we interrupted the protocol owing to lack of patient consent, the graft was lost. No organ infections were reported during the therapy period. The rationale for use of ECP is related to the presence of mixed antibody and cell-mediated mechanisms in acute rejection episodes. ECP inhibits specific pathogenic T cells. Conclusion Our approach seemed to give good results in terms of graft survival and safety.

Background Use of expanded-criteria donors (ECDs) for kidney transplantation has progressively increased in the past years with the intent to improve the number of available grafts. However, it is still uncertain if ECD kidneys have worse survivals than standard-criteria ones. The aim of this study was to retrospectively analyze a cohort of ECD patients comparing the 2 subgroups of 50–59- and >60-year-old donors in terms of donor, recipient, and transplant features and survival rates. Methods Ninety-one cases were analyzed. The cohort was stratified into 2 subgroups according to donor age: group 1, age 50–59 years (n = 26); and group 2, age ≥60 years (n = 67). Results Group 2 represented older donors and a higher percentage of donors with a previous history of hypertension. In Group 1, preharvest creatinine values showed higher results. No difference was detected regarding patient and graft survivals, with 5-year survival rates of 92.3% versus 86.7%, and 70.8% versus 69.8%, respectively. The best way to select the donors is still under debate. In our experience, a biopsy-driven selection was performed exclusively for group 2 ECDs. Considering the similar survivals obtained, we speculated that an accurate biopsy-based selection of older grafts allows one to avoid “bad” donors from the allocation system, thereby obtaining improved survival results. Conclusions Biopsy-driven pretransplantation selection appears to be the main system to optimize results, to achieve outcomes similar to nonbiopsied younger donors. Routine biopsies also in the younger subgroup of ECD may achieve a further improvement in survival.

Starting from the report on medical errors published in 1999 by the US Institute of Medicine, a number of different approaches to risk management have been developed for maximum risk reduction in health care activities. The health care authorities in many countries have focused attention on patient safety, employing action research programs that are based on quite different principles. Materials and Methods We performed a systematic Medline research of the literature since 1999. The following key words were used, also combining boolean operators and medical subheading terms: “adverse event,” “risk management,” “error,” and “governance.” Studies published in the last 5 years were particularly classified in various groups: risk management in health care systems; safety in specific hospital activities; and health care institutions' official documents. Methods of action researches have been analysed and their characteristics compared. Their suitability for safety development in donation, retrieval, and transplantation processes were discussed in the reality of the Italian transplant network. Discussion Some action researches and studies were dedicated to entire national healthcare systems, whereas others focused on specific risks. Many research programs have undergone critical review in the literature. Retrospective analysis has centered on so-called sentinel events to particularly analyze only a minor portion of the organizational phenomena, which can be the origin of an adverse event, an incident, or an error. Sentinel events give useful information if they are studied in highly engineered and standardized organizations like laboratories or tissue establishments, but they show several limits in the analysis of organ donation, retrieval, and transplantation processes, which are characterized by prevailing human factors, with high intrinsic risk and variability. Thus, they are poorly effective to deliver sure elements to base safety management improvement programs, especially regarding multidisciplinary systems with high complexity. Conclusion In organ transplantation, the possibility to increase safety seems greater using proactive research, mainly centred on organizational processes together with retrospective analyses but not limited to sentinel event reports.

Delayed graft function (DGF) represents one of the most common complications after kidney transplantation. The increased use of expanded criteria donors (ECD) is related to a greater risk for DGF. The objective of our study was to analyze the incidence of DGF among ECD versus standard criteria donors (SCD). Among 121 cases we obtained 2 groups: group A (SCD; n = 75) and group B (ECD; n = 46). Group B was composed of older donors (P.0001), with an increased incidence of diabetes mellitus (DM; P.0001), arterial hypertension (AH; P.0001), cerebrovascular accidents (P = .013), and lower creatinine clearances (CrCl; P = .008). Recipient age was significantly lower among group A (P.0001), with an increased incidence of donor hypotensive episodes (P = .016). The global incidence of DGF was 40 patients (33%), who were mainly in group B (P = .004). Analyzing the entire population, donor ageor= 60 years (P = .005), CrCl40 mL/min (P = .025), donor history of DM (P = .026) and AH (P = .017), and cold ischemia time15 hours (P.0001) were parameters related to increased incidences of DGF. A biopsy score of 3 was not significantly associated with DGF. The results of our study underlined the increased risk for DGF related to the use of ECD. Donor ageor= 60 years and cold ischemia time15 hours showed strong associations with this complication.

Background The Organizzazione Centro-Sud Trapianti (OCST) was set up in 1998 to coordinate the organ procurement and transplantation activity of 9 italian regions (Abruzzo, Basilicata, Calabria, Campania, Lazio, Molise, Sardinia, Sicily, and Umbria), each referring to a local Regional Transplant Center. The aim of the present study was to estimate organ donation and transplantation rates in the OCST from 1999 to March 2004. Materials and Methods A retrospective study of organ donors and transplantation activity in the OCST during the study period was performed, pointing out donor epidemiological data, such as age and sex ratio, causes of death, reasons for discarding, and transplantation rates. Donors reported to the OCST were divided into 6 groups: A (October 1998–December 1999), B (2000), C (2001), D (2002), E (2003), and F (January–March 2004). Results From 1999 to March 2004, 2272 potential donors were reported to the OCST. The nonharvested donors rate increased up to 52% (Group F), which was lower than the previous period (Group E, 64%), but higher than in 1999 (Group A, 43%). The major contributing factor was family opposition, which was 38% in 2002 and 41% in 2003. Conclusions The introduction of the OCST into the field of organ transplantation has yielded an increase in organ donation and transplantation activity within the regions that set it up from 1999–2003. This trend is a consequence of the growth of reported donors from the intensive care unit, which grew 12.7% from 2002 to 2003. From the data analysis of the first months of 2004, we expect confirmation of this trend.

The Italian national transplantation network has set up programs for liver, heart, and lung transplantation in urgent conditions. The aim of this study was to analyze the capability of these programs to meeting needs and their quality. In period between 2008 and 2011, the total number of urgent transplant requests was analyzed by organ, reason, and outcome, namely waiting time, graft origin, and number of transplantations with their one- and three-year graft survivals. There were urgent requests for 312 livers, 268 hearts, and 43 lungs totted among which 72%, 63%, and 79% were met, respectively. Actuarial graft survival rates at one and three years were 62% and 61% for liver and 73.1% and 70.5% for heart transplantations, respectively. The rate of satisfied requests and the graft outcomes showed that the national urgency programs meet the healthcare needs of patients with a short life expectancy, achieving good quality donor-recipient match.

Introduction From 2011 a program was developed for liver transplant recipients with Model for End-Stage Liver Disease (MELD) score ≥30. We examined its effectiveness and impact on the other subjects on the waiting list. Materials and Methods We analyzed requests received between January 2011 and May 2012 for the primary pathology, the outcome, the average waiting time, and the origin of the organ. We examined the ordinary waiting list for mortality rates and numbers of transplantations over this period (group A) versus a comparable preceding period (group B). Results There were 38 requests for 33 patients. Their primary pathologies were cirrhosis associated with viral infection ( n = 15), delayed graft failure (DGF; n = 5), biliary cirrhosis ( n = 4), hepatocellular carcinoma (HCC; n = 3 including 2 with cirrhosis), cryptogenic cirrhosis ( n = 3), postalcoholic cirrhosis ( n = 2), metabolic disease ( n = 2), and iatrogenic disease ( n = 1). Of the requests, 25 were successfully dealt with, whereas 5 requests were temporarily suspended and 2 were permanently suspended because of better or worse patient conditions. There were 6 deceased patients. Transplanted organs came from the inter-regional area in 64% of cases. The average waiting time was 5.9 days. Within group A were a 311 transplantations among 723 waiting list patients on with a 13.7% mortality rate. Within group B were 305 transplantations among 871 wait-listed patients with a 14% mortality rate. Discussion The liver transplantation program for recipients with MELD scores ≥30 allowed recipients in critical condition to receive grafts without altering substantially the opportunities for recipients on the elective waiting list.

Law number 91, dated April 1, 1999, established an organizational model for the activities of donation, retrieval, and transplantation of organs consisting of 4 levels: national, interregional, regional, and local. After 12 years this organizational project, called the "National Transplant Network," has reached an excellent level of effectiveness and efficiency. Since 2001 regional administrative districts have been entrusted increasingly with responsibilities concerning health. In 2008 health federalism was approved and in 2010 the federal health fiscal system entered in force. In a country with a federal organization, where regional districts are completely autonomous, is there a reason to still have a national transplant center and 3 interregional transplantation centers? We have developed a hypothesis on the function of Interregional Transplant Centers (CIR). The risk of federalism is the fragmentation of the National Healthcare System. To adequately meet the needs of citizens, smaller regions should sign agreements with larger regions regarding transplantation programs that require a large pool of donors whereas they could retain management of patients during the presurgery and postsurgery phases. The CIR should be committed to increase organ donation, to establish shared protocols and procedures, to disseminate knowledge, and to ensure equal access to health care. In conclusion, the adoption of health and fiscal federalism provides an opportunity to build healthcare systems to optimize resources. The network model should be kept but it is necessary to overcome localism and create positive federalism.

Introduction In 2005 the Italian National Transplant Centre (CNT) signed a cooperation agreement with the Hellenic Transplant Organization (HTO) fostering the transfer and transplantation of urgent Greek liver patients at Italian transplantation centers. So as to not reduce access to transplantation for Italian patients, the agreement provided compensation for organs allocated to Greek transplant recipients. The aim of this study was to analyze the flow of patients from Greece to Italy and the number of received livers to consider the possibility to extend this kind of agreement to other countries, so that this should not penalize Italian recipients. Materials and Methods The agreement provides the possibility for Greek patients affected by acute disease to be transferred to Italian transplantation centers participating in the agreement. Until 2008 livers transplanted into Greek recipients were returned through a preferential offer of surplus Greek organs, whereas from 2009 an obligation of payback was introduced. Results During the reviewed period requests for transfer, transferred patients, and number of patients who later underwent transplantation in Italy were 56, 26, and 23, respectively. Livers offered by the Greek organization that were accepted, transferred, and transplanted in Italy have been 82, 50, and 44, respectively. Discussion and Conclusions According to our analysis, the cooperation has had as positive impact for both Greece, which has difficulties transplanting urgent recipient because of the low number of donors, and for Italy, which is not penalized by the use of an organ in a Greek recipients, but is also rewarded for helpfulness.

Recurrent hepatitis C virus (HCV) is a major cause of liver transplant loss, hepatic failure, and retransplantation need. Posttransplantation antiviral therapy in patients with evidence of recurrent disease is the mainstay of management. Although HCV is a hepatocellular pathogen, there is increasing evidence that the virus can infect and persist in other cells. In particular, granulocytes and monocytes/macrophages are known to constitute extrahepatic sites for HCV replication and dissemination. The aim of this study was to apply Adacolumn apheresis as a possible therapeutic alternative to conventional drug therapy to manage HCV infections. Seven patients who underwent liver transplantation for HCV-related cirrhosis were eligible for the study. The patients underwent 5 1-hour sessions for 5 consecutive days. The first treatment was performed in the anhepatic phase of liver transplantation with the intent to early reduce infected granulocytes and monocytes/macrophages. The patients were evaluated over the 5 days after inclusion with 3- and 6-months follow-ups. Early apheresis treatments in the anhepatic phase and over the following 4 days after transplantation produced low viral loads in 4 patients, negative viral loads in 2 patients, and increased viremia in 1 patient. At follow-up, the viremia load was stable in 6 patients without increased transaminase levels. At the end of the treatment cycle, almost all immune cells of the 6 patients maintained CD4+/CD8+ T-cell ratios. The optimal timing of treatment initiation is unknown, but early preemptive therapy is recommended to decrease the risk for recurrent infection. Although this study investigated the responses among a small number of patients, it documented that the Adacolumn changed cellular immunity, promoting early virologic responses.

The 21 heart transplantations in Centre-Sud Transplant Organization (OCST) is a stable number despite increasing donations, especially among subjects aged 50 to 60 years. The aim of the present study was to evaluate the possibility to increase the usage of marginal hearts through dipyridamole ecostress. From 2008 to 2010 we analyzed OCST donors at 74 donation sites for echocardiography (31 yes versus 43 no) and heart utilization: (1) principal sites (n13) versus (2) minor sites (n13). Among 2145 signaled donors, there were 900 (42%) effective donors, including 816 (38%) utilized organs from 387 subjects of age50 years; 189, 50 to 60 years and 240,60 years with 217 (90%); 24 (10%), and 3 (1%) utilized hearts respectively to the analyzed sites, the utilized donors with echocardiography were 373: 259 (69.4%) versus 114 (30.5%) from those without such a service. Utilized donors between 50 and 60 years came from principal sites (n = 50), minor sites (n = 7) or those without an echocardiagram (n = 16). Utilized heart donors in each type of site were eight, one, and six, respectively. We believe that it may be possible to increase the total number of heart transplantations using dipyridamole stress-test echocardiography at the sites with major retrieval activity to increase heart transplantation among donors in the age range of 50 to 60 years.

The aim of the study was to evaluate the experience of the Centre-Sud Transplant Organization (OCST) area using cadaveric donor with neoplastic diseases to evaluate the possibility of transmission to recipients. From January 1, 2003, to December 31, 2010, the neoplastic risk has been reported to be 5.4% (377/4654 referred donors). In 2003, the number of donors with a tumor and their mean age were respectively: 60 (10.3%) and 59.6 ± 19.9; 2004: 33 (5.2%) and 61.4 ± 15.9; 2005: 32 (6%) and 62.8 ± 15.5; 2006: 46 (7%) and 60.7 ± 19.1; 2007: 51 (7%) and 58.9 ± 16; in 2008: 58 (7%) and 59.7 ± 19.6; 2009: 47 (7%) and 57 ± 26; 2010: 49 (7%) and 64 ± 16. The organ most affected by tumor has been the central nervous system (18%). The tumor was diagnosed before in 325 (86%) cases, versus during organ retrieval in 48 (12.7%) donor operations but before, which four cases (1%) occured after transplantation. According to the histological types and grades, 28 evaluated donors (8.2%) were suitable for transplantation. The histological types were: thyroid carcinoma (n = 3); prostate carcinoma (n = 8), renal clear cell carcinoma (n = 7), oncocytoma (n = 1), meningiomas (n = 2), dermofibrosarcoma (n = 1); verrucous carcinoma of the vulva (n = 1), colon adenocarcinoma (n = 1), grade II astrocytoma (n = 1), adrenal gland tumor (n = 1), gastric GIST (n = 1), oligodendroglioma (n = 1). Forty-five organs were retrieved (22 livers, 19 kidneys, 3 hearts, and 1 pancreas) and transplanted into 44 recipients with 1 liver-kidney combined transplantation. Four recipients died due to causes not related to the tumor. No donor-transmitted tumor was detected among the recipients. Donation is absolutely not indicated in cases of tumors with high metastatic potential and high grades. Performing an accurate evaluation of the donor, taking into account the histological grade, currently can allow, organ retrieval and transplantation with an acceptable risk.

Background. In kidney transplantations, the identification of early postoperative parameters with high predictive power for the development of late allograft dysfunction has important implications for clinical practice. This study sought to determine these parameters in a single-center cohort. Methods. We studied 82 deceased donor renal transplantation. We assessed the following measures: dialysis-dependent delayed graft function (ddDGF), extended DGF, serum creatinine level at day 7, creatinine reduction ratio at day 7, urine output at day 1 and at day 7 posttransplantation (U07). Results. Only UO7 showed a significant result upon multivariate analysis (P < .0001). It was less influenced by dialysis with respect to measures based upon serum creatinine. By Receiver Operating characteristic (ROC) analysis, it showed an elevated area under the curve (0.811), with a cut-off value of 500 mL/24 h, showing high sensitivity (98.5%). Conclusions. UO7 may be of clinical utility to assess the risk for subsequent renal dysfunction.

Introduction Patients who have undergone kidney transplantation and suffer from hepatitis C (HCV) cannot be treated with standard therapy (pegylated interferon combined with ribavirin) due to the risk of acute rejection. Furthermore, immunosuppressive therapy facilitates the progression of infection and chronic hepatopathies. Monocytes and macrophages are known to produce extrahepatic breeding sites that spread disease. Our aim was to reduce macrophages, granulocytes, monocytes, proinflammatory cells, and viremia levels using an extracorporeal device: Adacolumn Leukocyte Apheresis (Otzuka Electronics, Japan). Methods The Adalcolumn filter is filled with 2-mm cellulose acetate beads immersed in sterile saline solution. These carriers absorb granulocytes and monocytes/macrophanges through their FCR receptors. Six patients affected by viral genotype 1b underwent five 1-hour treatments for 5 consecutive days. Results Viremia was reduced in Patients 1, 2, 4, and 6 in association with decreased pro-inflammatory cytokine levels and a normal CD4/CD8 T-cell ratio, after 3 months. Subjects 1 and 3 showed inverted CD4 + /CD8 + T-cell ratios, which changed at 4-month follow-up in only patient 1. Subject 5 did not show any changes. Conclusions The treatment was safe without hemodynamic or infectious complications, suggesting that this method could be used in a greater number of patients to evaluate amelioration of increased viremia.

The Italian Gate to Europe (IGE) was established in April 2005 to supply a single national coordinating center for the exchange of organs and patients with the rest of Europe. When an organ is offered from Italy, the IGE ascribes it to the first foreign organization that accepts it on a first-come, first-served basis. In the case of offers from abroad, the IGE allocates the organ to one of the three Italian Interregional Centres in rotation. On the basis of international agreements, the IGE also manages the transfer of foreign patients to Italian transplant centers. The first 15 months of activity have been compared with the previous period of the same length. The IGE managed 353 contacts. 53 organs were transplanted in Italy versus 19 in the previous period. Seven foreign patients received liver transplantations in Italy. The increase in imported organs could be a function of IGE creation, since it allowed a reduced response time to offers and guaranteed the participation of all Italian centers in the program of international exchanges with a subsequent increase in the pool of recipients and equitable distribution of transplanted organs. The drop in the number of exported organs was a probable a consequence of increased acceptance criteria of Italian centers. The mentioned international agreements have allowed us to better meet the health care needs of foreign citizens who live in countries with low per-million-population donation rates with no detriment to the probability of Italian citizens being transplanted.

Background The Organizzazione Centro-Sud Trapianti (OCST), which was created in 1998, is organized into eight regional areas, each referring to a local Regional Transplant Coordinating Center. Organs are primarily allocated to meet the demands of transplant centers in each regional area. Urgencies, pediatric grafts, and paybacks are managed by an Interregional Transplant Coordinating Center. The aim of the current work is to report on the impact of introduction of OCST on organ donation and transplant activity over the period from 1999 to 2002. Materials and methods A retrospective analysis of donor and transplant data charts over the period from 1999 to 2002 focused on outcome analysis based on donor epidemiological data, cause of death, reasons for discards and grafts performed at OCST local transplant centers. Results From 1999 to 2002, we observed a remarkable increase in organ donation from 8.8 to 22.5 donors per million people. Donor epidemiology showed an increase in median age and stroke incidence rates and a decrease in trauma cases. The nonharvested donor rate rose steadily over the study period, plateauing at 58%, which was compensated for by a threefold increase in donation. Family oppositions ranged as high as 35.5% on average, despite public efforts to support donation. Transplant activity rose by 76%. Conclusions The institution of OCST and the efforts from central and regional authorities have yielded a significant increase in organ donation and transplant activity rates over the period from 1999 to 2002. Major areas of concern are the high opposition rate and the decreasing quality of harvested grafts. Long-term analysis is underway to assess the impact of OCST on the quality of transplants performed in the catchment area.

Background. Transplantation from living donors, in Italy, is still not accepted, in particular those from unrelated donors. The aim of this paper was to present the experience of one transplant center. Materials and methods. Since 1982, 608 transplants were performed from living donors using cyclosporine as the main component of immunosuppressive therapy. Among those, 402 transplants were from related living donors (338 one haplotype pairs and 25 zero haplotypes pairs) and 206 from unrelated living donors (171 spouses and 35 emotionally related subjects). Results. Graft survival at 1, 5, and 10 years showed no statistically meaningful difference between the two groups. A group of 19 transplants performed in predialytic phase patients was compared with a contemporaneous group of 167 transplants performed in patients who were already receiving dialysis. These two groups did not show any statistically meaningful difference in graft survival at 1, 5, or 10 years. Discussion and conclusions. We think that transplants from living donors, whether related or unrelated, must always be proposed as a therapeutic option for end-stage renal disease patients, since they show an higher graft survival than that from cadaveric donors, independent of the compatibility between donor and recipient and independent of the degree of relationship of the pair. Transplantation from living donors definitely is a complementary, not substitutive, program to that from cadaveric donors, which should always be encouraged with awareness campaigns among the population and targeted programs for healthy personnel.

Validity of living donor kidney transplantation is universally accepted. In contrast, after enthusiastic adoption in the 1990s, living donor liver transplantation has decreased in recent years. The aim of the present study was to evaluate retrospectively the current use of this form of donation in Italy by comparing liver and kidney cadaveric and living donations from 2002 to 2010. The number of liver transplantations from living donors has decreased from 34 in 2002 (3.9% of total) to 13 in 2010 (1.3% of total). In contrast, kidney transplantation from living donors increased from 126 (7.9% of total) to 186 (11% of total). We observed that living donations for kidney transplantation are still underused, especially with unrelated donors. Living donor liver transplantation has decreased in recent years; this procedure should be reserved to centers with particular expertise. It would be appropriate to implement programs to increase the attention of health professionals and the general population and to integrate living donations into programs of deceased organ donation.

Patients with focal segmental glomerulosclerosis (FSGS) develop nephrotic syndrome and terminal renal failure in most cases. FSGS reappears in 15-50% of transplanted kidneys and frequently causes the graft loss. Sera from patients with FSGS of native or transplanted kidneys contain some proteinuric or permeability factors (PF) which can be removed by means of plasma exchange (PE) or protein A Immunoadsorption (IA).We suggest a therapeutic protocol, for patients with biopsy proven FSGS of native or transplanted kidneys, resistant to steroid and immunosuppressive therapy, based on the association of PE or IA to conventional drug therapy. Daily proteinuria, renal function, serum albumin and circulating level of proteinuric factors (permeability test) will be monitored at regular time intervals during the apheresis cycle, which will be intensive at the beginning (8-10 sessions in 4 weeks) and very gradually discontinued. Results. We will consider satisfactory remission the reduction of proteinuria below 1 g/day, improvement of renal function, normalization of serum albumin level (3.5 g/dl). Partial remission will be considered: proteinuria below 3 g/day, stable renal function, serum albumin level between 3 and 3.5 g/dl. Permeability test, if positive at baseline examination, should be negative after apheresis.The primary endpoint of our protocol is: lasting remission (satisfactory or partial) after the apheresis suspension. Secondary endpoints are: maintained remission with continuing apheresis sessions, correlation between permeability activity and disease activity, identification of responders and non responders patients on the basis of positive permeability test.

TRANSPLANTATON has been the choice option to treat successfully an increasing number of acute and chronic human pathologies with declining morbidity and mortality. However, availability of organs from human donors is limited and dramatically inadequate with respect to patient requests. Xenotransplantation from large-sized mammals has thus been reconsidered as a tool to overcome the present unbalance between organ offers and requests. Pigs have been chosen because they can be easily and cheaply bred; they do not raise ethical questions—their use as alimentary resources is generally admitted; and they possess organs largely human compatible for size, anatomical organization, and physiology. Nevertheless, this option is usually compromised by the occurrence of an irreversible hyperacute vascular rejection of the animal transplanted organ as soon as it is perfused with human blood, mediated by natural preformed antibodies and by the activation of the complement cascade. Downregulating the complement system by expressing on the surface of the swine organs one or more species-specific negative modulators of the complement complexes, such as human decay accelerating factor (hDAF), could prevent the rejection of the graft. Our group has obtained a number of transgenic pigs for hDAF using sperm-mediated gene transfer (SMGT), an innovative and highly efficient and reproducible method. In SMGT, spermatozoa are employed as natural vectors of foreign DNA and are bound, captured, and internalized into recipient egg cells to generate a genetically modified progeny. Revealing the expression of the protein on the surface of the organs is an important confirmation for successful transgenesis. The aim of this report is to show, by immunohistochemical detection, the expression of hDAF in transgenic hearts, organs maximally eligible for xenotransplantation.

In Italy, all donation and transplant activities were officially disciplined in 1999 by the law 91 of April 1, 1999. This law enacted a coordinator-based model of transplantation, instituted the National Center for Transplantation (Centro Nazionale Trapianti-CNT), and endorsed the existing interregional transplant agencies (ITA), such as the Nord Italia Transplant program (NITp), the Associazione InterRegionale Trapianti (AIRT), and the Organizzazione Centro-Sud Trapianti (OCST). Within its borders each ITA has adopted its own organizational model; there is no overt centralized control exerted by the CNT according to the law 91/1999. The aim of the current work is to report on the organizational model adopted by OCST, the ITA gathering the Italian regions of Abruzzo, Basilicata, Calabria, Campania, Latium, Molise, Sardinia, Sicily, and Umbria.

(3.9 ng/ml), CLD (6.8 ng/ml), healthy control (6.6 ng/ml), [p = 0.02, 0.001, 0.001]. The Hepcidin/Iron ratio was found to be lowest (3.9%) in ACLF-MOF, compared to ACLF (19%) and CLD (22%) [p < 0.01], Hepcidin/ferritin ratio was similarly lowest in ACLF-MOF (6.1%) than in ACLF (12%) or CLD (51%) [p< 0.01]. Hepcidin/transferrin ratio was again lowest (37%) in ACLF-MOF than ACLF (84%), CLD (90%) [p < 0.01] and the ratio of Hepcidin/ceruloplasmin was 35%, 62% and 93% [