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Organ transplantation is a life-saving procedure for many patients. However, every year a large number of patients die on the waiting lists due to the shortage of available organs. Thus the organ scarcity problem has been the starting point for reflecting on the effectiveness of the current transplantation system based on willingness to donate and altruism. The analysis of the evolution of the Italian transplantation discipline gives the opportunity to focus on the reform perspectives of the organ procurement system aimed at changing the consent mechanism and the prohibition of organ commercialization. In the recent years, the debate on the scarcity problem has shift from those traditional perspectives to a new one that includes heterogeneous ways to reduce the shortage of organs such as the use of marginal donors, the crossover technique and the reciprocity principle for organ allocation., BioLaw Journal - Rivista di BioDiritto, N. 4 (2021)

Renal transplantation (RTx) is at the moment the best therapy for end stage renal disease. In recent years, the increase of the global knowledge about immunology and RTx complications allowed a significant increase in the duration of RTx and in patients’ survival. RTx ultrasound gives to transplant clinicians the possibility of carrying out a structural monitoring of the graft from the beginning throughout the duration of the RTx. Then, ultrasound is a first-level method that all clinicians should be able to perform and interpret. In this paper we will present some basic concepts about the ultrasound image of the “healthy” transplanted kidney, relating them to the main pathological pictures that may occur during a clinical-ultrasound monitoring of the RTx. Finally, some concepts regarding the use and usefulness of ultrasound with contrast media (CEUS) in the evaluation and the follow-up of RTx will be discussed.

Introduction. Over the past two decades, our thinking has changed from considering rejection as primarily a T-cell mediated process to the realization that insufficient control of the humoral arm of a recipient’s immune system is the factor primarily responsible for the allograft dysfunction and loss. Acute Antibody Mediated Rejection (ABMR) in kidney transplantation is a severe complication that frequently occurs after transplantation and is due either to pre-transplant Donor Specific Antibodies (DSAs) or to de novo DSAs. New techniques to detect DSAs in the recipient serum and advances in the assessment of graft pathology have allowed us to recognize this entity in recent years. Methods. The treatment of ABMR is a multistep process consisting in the desensitization of the patients with preformed antibodies to prevent acute ABMR: in case of acute ABMR, the antibodies are removed from the serum and anti-B cells immunosuppressants are used. Results and Discussion. Along with our knowledge on acute ABMR, a distinct entity has been recognized: the chronic AMBR. Chronic ABMR is a frequent cause of late graft dysfunction and is characterized by a typical histopathologic feature. The treatment is often difficult and new drugs are now tested to control the disease.

The incidence of acute rejection of the kidney allograft in the world has been around 15% during the period between 2001 and 2003. It is clinically defined as an elevation in the level of serum creatinine by more than 0.3 mg/dL and is diagnosed by kidney biopsy. On pathologic examination, the interstitium of the allograft is diffusely edematous and infiltrated by CD4 and CD8 lymphocytes. Tubulitis occurs when the lymphocytes and monocytes extend into the walls and lumina of the tubules. Presence of leukocytes determines infection or antibody-mediated rejection. Typically C4d staining is negative. Other causes of acute allograft dysfunction included prerenal factors, interstitial nephritis, infection, acute tubular necrosis, toxicity by drugs, and obstruction in the urinary tract. The primary diagnostic assessments include history, especially adherence to immunosuppressive therapy, physical examination, blood and urine laboratory tests, measurement of the serum levels of the drugs, and ultrasonography. Diagnosis of acute cellular rejection depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte, and proteomic study. Treatment of acute cellular rejection in kidney transplant recipients include pulse steroid for the first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 are used as the second line of treatment if graft function is deteriorating. Changing the protocol from cyclosporine to tacrolimus or adding mycophenolate mofetil or sirolimus might be effective. Prognosis depends on number of rejection episodes, the use of potent drugs, time of rejection from transplantation, and response to treatment.

Immunosuppressive therapy in renal transplantation Immunosuppressive therapy in renal transplantation can be distinguished in induction therapy and maintenance therapy. Induction therapy is an intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, the induction immunosuppressive strategies used at kidney transplant centers fall into one of these two categories. One strategy relies upon high doses of conventional immunosuppressive agents, while the other utilizes antibodies directed against T-cell antigens in combination with lower doses of conventional agents. Maintenance immunosuppressive therapy is administered to almost all kidney transplant recipients to help prevent acute rejection and loss of the renal allograft. Although an adequate level of immunosuppression is required to dampen the immune response to the allograft, the level of chronic immunosuppression is decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy; these risks directly correlate with the degree of overall immunosuppression. The optimal maintenance immunosuppressive therapy in kidney transplantation is not established. The major immunosuppressive agents that are available in various combination regimens are glucocorticoids (primarily oral prednisone), azathioprine, mycophenolate mofetil (MMF), enteric-coated mycophenolate sodium (EC-MPS), cyclosporine (in non-modified or modified [microemulsion] form), Tacrolimus, everolimus, rapamycin (sirolimus), and Belatacept.

Kidney transplantation is the optimal treatment for selected patients with end-stage kidney failure. However, the demand for kidney transplantation exceeds the supply of organs available. At the beginning of the twenty-first century, in an attempt to increase the pool of deceased donor organs and reduce organ discard rates, kidney transplant programs have been developed using Expanded Criteria Donor kidneys, for Single or Dual Kidney Transplantation, and kidneys from Donation after Circulatory Death. Moreover, for appropriately selected candidates, are now offered organs from donors with increased but “acceptable” risk profile for the transmission of infectious and neoplastic diseases. Based on this reality, to date, the assessment of eligibility for a deceased donor to kidney transplantation is complex and requires a multidisciplinary approach through each step of the donation process. In this review, we outline the various modalities of kidney transplantation from a deceased donor. We also report the eligibility criteria based on the donor profile for diseases transmissible to the recipient, and the scores based on donor characteristics and histology criteria from kidney biopsies that are currently used to refine the quality of organs used for transplantation.

Novel strategy in living donor kidney transplantation to outcome biological barriersLiving donor kidney transplantation (LKD) is considered the best type of transplant for end-stage renal disease p...

Kidney transplant is the replacement treatment of choice in ADPKD patients with end-stage renal failure. However, the possible coexistence of potential risk factors for serious complications requires careful clinical evaluation and particular preparation of the ADPKD patient who is a candidate for transplantation. This article will take into consideration the main problems an ADPKD patient may present, their possible treatment, and the need for other routine evaluations (clinical, laboratory and instrumental) to exclude the presence of relative or absolute contraindications in kidney transplant candidates.

Galectin-3 is a 32- to 35-kDa member of the galectin family of b-galactoside-binding lectins, which is characterized by a carbohydrate recognition domain. Through its carbohydrate-binding function, it regulates cell growth, differentiation, and inflammation. It also plays a complex, context-dependent role in the kidneys. During the development, it promotes nephrogenesis and is strongly expressed in the ureteric bud and its derivatives. An increase in the concentration of galectin-3 has been reported to be associated with fibrosis of the kidneys. Elevated levels of plasma galectin-3 are also associated with increased risks of rapid renal function decline, incident chronic kidney disease, and progressive renal impairment, and also with cardiovascular endpoints, infection, and all-cause mortality in patients with renal function impairment. This review discusses a general survey on galectin-3 expressions in nephrogenesis, kidney injury in animal models, clinical renal diseases, and renal transplantation and the potential role of galectin-3 for treatment in kidney disease. (Cardionephrology)

Bariatric surgery represents the elective treatment of severe obesity (BMI≥40Kg/m2) since it results in better control of cardiovascular risk factors and comorbidities typically associated with obesity, like diabetes, hypertension and dyslipidemia. Obesity is a recognized independent risk factor for chronic kidney disease and for progression of renal insufficiency. Pathomechanisms are still incompletely known. Obesity is associated with hyper-filtration, microalbuminuria and proteinuria all of which favor renal disease and its progression. This narrative review reports on the available evidence linking bariatric surgery and renal function since this surgery may affect proteinuria, hyper-filtration and glomerular filtration rate. Although available data are limited in particular in cases with more advanced stages of renal failure, bariatric surgery associates with improved filtration and lower proteinuria in patients with mild to moderate renal insufficiency. In patients with more advanced stages of renal failure, surgery should be considered if obesity represents a relative contraindication to transplantation. Surgery seems to improve graft survival. Further, nephrologists should be informed on the metabolic and nutritional changes associated with bariatric surgery, which could be responsible for untoward effects requiring early identification and treatment. Bariatric surgery could be a valid therapeutic option in renal patients to improve the negative clinical outcomes of obese subjects.

Introduction: Renal transplantation is the best treatment for most patients with chronic renal failure at an advanced stage. In recent years, in response to the reduced availability of organs, the eligibility criteria for donation have been expanted and living donor transplantation was implemented, too. Transplant system complexity and problems occurring after transplantation require a greater expertise in clinical care. The analysis of transplant patient's experience is important for the identification of patient's needs and for the prevention of complications. Materials and methods: Research studies last 15 years through databases Pubmed and CINAHL. Search through institutional websites is useful for statistical data and legal references. Results: 17 items have been selected on the quality of life and transplant patient's experience. A critical analysis of the content has been made through a division into five thematic areas: organ donation, legal nursing skills, psycho-social and relational components, clinical care components, outcome data. Conclusions: The pathway to an optimal health state after the transplant is long and sometimes hampered by complications such as rejection, infections, cancers and disorders of the psychic sphere. The problems that occur gradually over time are the reconstruction of the image of the self and of the identity, the concerns about the origins of the kidney, the management of complications, the adherence to therapy and the relationship with the family and any living donor. For a proper long-term plan a stronger nursing role in decision-making together with a well organized outpatient follow-up service is of great importance, supported by a multidisciplinary team for specific complications (adherence to the requirements: diet, therapy, hygiene).

The process of expansion and rooting of Mafia associations beyond their traditional areas represents a crucial issue for the scientific literature on organized crime. In this regard, Federico Varese’s book, Mafias on the move. How Organized Crime Conquers New Territories, provides a crucial insight which allows to address the question how Mafia associations manage to transplant in new places. Based on a comparative analysis, the author addresses his attention to several case studies, which show examples of successful (or not) infiltration of organized crime groups into new territories and societies. Among the various variables taken into consideration, the main factor determining Mafia transplantation consists in organized crime’s ability to provide protection to several legal (as well as illegal) players operating within a context of unregulated markets.

Tooth transplantation or intentional replantation could be considered as a viable therapeutic options for rehabilitating posteriorior area of young patients with a seriously damaged or lost permanent molar. If its conservative restoration would result complex and with an unfavorable long-term prognosis, due to patients young age implant or prosthetic solutions would require different remakings over lifetime, in addition to long time necessary for the final prothesis delivery. The autotransplantation technique allows us to replace immediately the compromised or lost molar with an undamaged tooth and to preserve the benefits derived from the conservation of the periodontal ligament vitality. In intentional tooth replantation molars with an unsuccessfull endodontic treatment can be saved with a complete functional restitutio ad integrum. For this study we selected 10 patients who presented seriously compromised molars and at the same time partially or completly impacted wisdom tooth. In a single operatory session compromised teeth have been extracted and immediately replaced with the homolateral or controlateral impacted wisdom tooth removed with an atraumatic technique. All the transplanted elements have been stabilized with an extra-coronal splint for 4 weeks and afterwards devitalized immediately before the splint removal. For the teeth treated with intentional replantation together with the atraumatic extraction an apicoectomy and a subsequent retrofilling of all the roots was performed. Replanted teeth have seldom required a post operative splint, because of the general substantial primary stability obtained. The transplanted or replanted teeth have been monitored for one year after the treatment from both a periodontal and an endodontic point of view. All the dental elements 12 months after the procedure didn’t show any alteration of the periodontal reference parameters. No periapical lesion appeared in the same time, while the pre-existing ones resulted healed. All the teeth are functionally active with normal occlusal contacts. Intentional replantation and tooth transplantation procedures proved to be effective alternatives to traditional implant and prosthetic procedures.

Biological drugs represent one of the most important therapeutic novelties of the last twenty years in many areas including Nephrology. Their use was initially limited to the transplantation field, but now it is extended to the treatment of many glomerular diseases. The selectivity of these drugs should ensure a decrease in the side effects associated with conventional immunosuppressive therapy and an improvement in patient compliance. These aspects, together with the identification of previously unknown pathogenic mechanisms of many glomerular nephropathies, resulted in an increased use of biologic drugs even in kidney diseases. Rituximab was introduced in the mid '90s and it was the pioneering drug among biologic agents in Nephrology. Since then, clinincians have become more and more interested in this class of drugs, and the potential of these agents is on the rise. Currently unresolved issues include both safety and cost/benefit ratio of their long-term use. Undoubtedly, it is the most significant progress that has been made from a therapeutic point of view in recent years.

s / Digestive and Liver Disease 46 (2014) e71–e84 e73 QUANTIFICATION OF TACROLIMUS IN PBMCS SAMPLES IN PEDIATRIC LIVER TRANSPLANT PATIENTS AND CORRELATION WITH TACROLIMUS WHOLE BLOOD CONCENTRATION Michele Pinon1,∗, Pier Luigi Calvo1, Antonio D’Avolio2, Debora Pensi2, Andrea Brunati3, Roberto Canaparo4, Amedeo De Nicolo2, Giulia Carbonaro3, Alessia Cerrina3, Giovanni Di Perri2, Renato Romagnoli3, Cristiana Barbera1, Mauro Salizzoni3 1 Department of Pediatric Gastroenterology and Hepatology, Regina Margherita Children’s Hospital, Azienda Ospedaliera Citta della Salute e della Scienza, University of Turin, Turin, Italy 2 Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy 3 Liver Transplantation Center, Azienda Ospedaliera Citta della Salute e della Scienza, University of Turin, Turin, Italy 4 Department of Drug Science and Technology, University of Turin, Turin, Italy Objective: Therapeutic drug monitoring (TDM) of tacrolimus in whole blood is essential to optimize clinical outcomes and reduce toxicity. However, the relationship between blood concentrations and therapeutic efficacy is unclear, probably because it does not reflect tacrolimus concentration at the active site. In this preliminary study, our aims were to validate a newmethod for tacrolimus quantification into the target cells (peripheral blood mononuclear cells, PBMCs), in a cohort of 24 pediatric liver recipients after a median follow-up of 5.23 years. Moreover, we analyzed the influence of ABCB1 (3435C>T and 1199A>G), CYP3A*3 and CYP3A4*22 polymorphisms on the intralymphocyte distribution of tacrolimus. Methods: PBMCs were collected using CPT tubes; cells count and the mean cellular volume were evaluated with a coulter counter. Tacrolimus concentration was quantified, after cell lyses, using ultra performance liquid chromatographywith tandemmass inpositive ionmode, coupledwith thenewautomatedon-line solid phase extraction technology. Results: A median value of 49.5ng/mL (range 14.4–358.9) of tacrolimus PBMCs concentration was found, corresponding to a 12.7-fold wider range than the whole blood levels simultaneously analyzed. Although a significant correlation with mean tacrolimus blood levels could be observed, tacrolimus intracellular accumulation tended to be higher in ABCB1 G/A, although not statistically significantly, and in CYP3A5*3/*3 recipients. Conclusions:Although tacrolimus PBMCs concentration cannot be considered as a routine test yet, this method could bemore predictive of efficacy and toxicity of immunosuppressive therapy than whole blood levels. Further studies are required to evaluate the relationship with clinical outcomes. http://dx.doi.org/10.1016/j.dld.2014.07.025 LIVING DONOR LIVER TRANSPLANT (LDLT): THE PATIENT PERSPECTIVE Andrea Pietrobattista1,∗, Manila Candusso1, Maria Sole Basso1, Chiara Grimaldi2, Fabrizio Di Francesco2, Lidia Monti3, Jean De Ville De Goyet2, Giuliano Torre1 1 USC Epatogastroenterologia e Nutrizione, Ospedale Pediatrico Bambino Gesu, Roma, Italy 2 USC Chirurgia epato-biliare, Ospedale Pediatrico Bambino Gesu, Roma, Italy 3 USC Radiologia, Ospedale Pediatrico Bambino Gesu, Roma, Italy Objective: To evaluate the outcome of living liver donor transplantation in children. Methods: Retrospective analysis. Results: We performed 23 LDLTs out of 105 transplants in the past 5 years inRome, and thenumberhas been increasing; themain indication is cirrhosis in biliary atresia (20 cases, 87%) but it has been performed also in metabolic diseases such as primary oxalosis, MSUD and propionic academia. No recipient died, themean age at transplantwas 29.3months (SD 28.6, r. 6–132), themeanweight 13kg (SD6.7, r. 5.5–30.3), after amean144daywaiting list time (SD 250, r. 0–1040); the mean PELD score was 20 (SD 12, r. 0–38). The mean ischemic time was 244min in LDLT vs 517.3min in cadaveric transplants. The mother was the donor in 13 children, in one a relative; no death. Surgical complications occurred in 8 children (34.7%), 2 out of these in one baby; the rate is similar in cadaveric recipients (33.7%), Rejectionwasdiagnosed in47.8%of cases, biliary stenosis in 2 cases, resolved by percutaneous biliary drainage (1) and by surgery (1); one child reported portal thrombosis, treated by Meso-Rex shunt. No living donor reported any complication. Conclusions: LDLT is an important tool in dealing childrenwith end-stage liver disease, mainly if cadaveric donors are lacking; it could be a safe choose even in metabolic disorders, with an heterozygote donor. http://dx.doi.org/10.1016/j.dld.2014.07.026

Negli ultimi anni si assiste a un rinnovato interesse per l'emodialisi domiciliare nel trattamento dell'insufficienza renale cronica, anche grazie alle recenti innovazioni tecnologiche che consentono di effettuare tale trattamento più agevolmente che in passato. Il revival di questa metodica suscita un interessante dibattito nella comunità scientifica e tale dibattito ultimamente, in Italia, ha visto l'espressione di alcune posizioni critiche nella piattaforma NephroMEET. In questo contributo, si sottolineano le principali evidenze cliniche e gli effetti psicologici e sociali di questa metodica, attraverso un approfondimento della letteratura più recente e grazie all'analisi conversazionale di un caso di successo. La prospettiva da cui si parte è quella relativa al concetto di salute, come definito dall'OMS. Si evidenzia come l'emodialisi extracorporea domiciliare presenti importanti vantaggi sia clinici che psicosociali, configurandosi come una valida alternativa dopo il trapianto e la dialisi peritoneale.

Presently pregnancy is no more exceptional in women with metabolic diseases. However, it still poses significant medical problems both before and after childbirth. The challenge is even greater if the mother has undergone organ transplantation, because of her metabolic disease. We report on a case of pregnancy in a patient 29-year-old with methylmalonic acidemia cblA type (OMIM 251100) who received a renal transplantation at the age of 17 for end-stage renal disease (ESRD) caused by her primary disease. During pregnancy neither metabolic crises nor renal function changes were observed in the mother, with the only exception of a mild increase of her systemic blood pressure. To the fetus pregnancy was uneventful and during the first 30 months after birth the baby's neuropsychomotor development was normal and there were no episodes of metabolic derangement. This is evidence that methylmalonicacidemia cblA, even when treated with renal transplantation for inherent ESRD, is no contraindication to pregnancy. It is even possible that a functioning transplanted kidney contributes to improve metabolic parameters.

This study was prospectively aimed at having better information about the natural history of serum cytokines in cirrhotic patients undergoing liver transplant surgery and at assessing their ability to set up an appropriate dynamic relationship between pro-inflammation and anti-inflammation. The levels of six cytokines (TNF-α, IL-1, IL-2, IL-6, IL-8, IL-10) were measured in blood samples collected at different time points before, during and after (48 h) the transplant procedure from the radial artery of 62 consecutive cirrhotic patients who underwent orthotopic liver transplantation. IL-1 always stayed within the normal range; IL-2 showed elevated baseline levels but decreased up to half at the end of the study (p0.0001). IL-6 peaked at the end of surgery and returned to baseline 48 h afterwards. The same happened to IL-8 concentrations. IL-10 levels shown above the normal threshold at baseline, peaked at the end of surgery (p0.0001) and were halved at the end of the study (p0.0001). TNF-α peaked at the end of surgery without, however, being different from baseline levels (p=0.6). The physiologic pattern of cytokine release and their dynamic relationship was found to be preserved with a quick return to a balance between pro-inflammation and anti-inflammation as shown by the IL-6/IL-10 and TNF-α/IL 10 ratios (used to assess the inflammatory balance). A correlation was found between perioperative pro-inflammatory cytokine levels and the severity of the liver disease necessitating OLT. In summary, cirrhotic patients can achieve a balanced inflammatory response to surgery which is considered a primary requirement for uneventful grafts and patients' postoperative recovery.

Background NMR spectroscopy–based metabolomics is a system approach used to investigate the metabolic profile of biological fluids with multivariate data analysis tools. The aim of this study was to examine the kidney graft recovery process noninvasively through the examinations of urine samples using 1 H NMR spectroscopy combined with chemometric tools. Methods Urine samples were treated as the source of metabolites reflecting the pathological and clinical conditions of patients with transplanted kidneys. We observed 15 subjects (9 males and 6 females) during the graft recovery process and initial days thereafter. The patients provided at least 9 samples each, applying advanced statistical methods of analysis: Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis PLS-DA). Results The PCA model (for all subjects exp. var. PC1 13.96% and PC2 9.88%) allowed us to clearly designate 3 stages of recovery: initially the kidney is not working; in the second stage, it regains functions, and the third stage includes follow-up during hospitalization. PCA analysis of a single patient follows graft recovery based on biochemical (metabolites) information, assigning the appropriate recuperation stage. Conclusions NMR spectroscopy together with chemometric analysis allow monitoring of kidney graft recovery to identify patients who are not progressing within the normal range.

Introduction: Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long-term patient survival. Patients and methods: Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low-dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. Results: There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. Conclusion: There was no difference in incidence of bacterial infections and long-term patient survival between the two groups.

Background During the last few decades the mean age of subjects on chronic dialysis (CD) significantly increased. The effects of these changes on mortality rates, causes of death, early and long-term predictors for mortality have not yet been clarified. We analysed this issue through a study performed over a period of 12 years. Methods We studied 8977 patients enrolled on the Lazio Dialysis Registry (Italy) in 1995-2006. We analysed annual mortality rates, causes of death, probability and determinants of the survival. Results The overall mortality rate was 14.6 deaths (95% CI: 14.2-14.9) per 100 person-years on CD, remaining essentially unchanged over the 12-year period, despite a 5-year increase in the median age. A reduction in mortality was found for patients >74 years from 29.8 (95% CI: 24.8-34.9) in 1995 to 22.5 (95% CI: 20.0-25.1) in 2006. No statistically significant differences were found over time in annual mortality rates by cause of death. The probability of survival was 0.86 1 year after starting dialysis and 0.33 after 12 years. We found a higher association between haematocrit levels, serum albumin, self-sufficiency and survival within 1 year of dialysis and between diabetes and survival after 1 year. Conclusions The finding that the mortality rate of CD patients did not change over the last 12 years, despite concomitant and significant ageing of patients, supports the public health policy of providing CD to very old subjects. The identification of the clinical factors that predict survival underlines the role of clinicians in preventing and treating these conditions after the start of CD.

Risk factors associated with cardiovascular diseases reduce the availability of endothelial progenitor cells (EPC) by affecting their mobilization and integration into injured vascular sites. The existence of a bone marrow reservoir of EPC has attracted interest, especially as target for therapeutic intervention in different pathological settings. Among the cardiovascular risk factors, hypertension has been shown to be a strongest predictor of EPC migratory impairment. However, at present, data concerning EPC biology are still limited. In this article we provide an overview of data relevant to their potential clinical implications in cardiovascular disorders. In addition, the recent advances in understanding the role of EPC in the pathophysiology of hypertension are discussed.

New and often aggressive treatment schemes allow the successful healing of many young patients with cancer, but the price the young women have to pay is high: many of them lose ovarian function and fertility. Due to the improved long-term survival of adolescents and young women with malignancies undergoing gonadotoxic chemotherapy, preservation of future fertility has been the focus of recent ubiquitarian interest. A feasible solution is the cryopreservation of ovarian tissue. Ovarian tissue, after thawing, can be used in three different ways: 1. grafted into its normal site (orthotopic); 2. grafted into a site other than its normal position (heterotopic), necessitating recourse to in vitro fertilization (IVF); 3. grown and in vitro matured in order to obtain metaphase II oocytes for an IVF program. It is believed that protein supplementation, in cryopreservation solution, is essential for improving ovarian tissue cryopreservation. The aim of this study was to evaluate the ultrastructural appearance of human ovarian tissue cryopreserved in 1.5 M 1,2 propanediol (PROH), 0.2 M sucrose using different protein sources: fetal calf serum (FCS), plasmanate or syntetic serum substitute (SSS). Fresh and frozen/thawed ovarian tissues were compared by transmission electron microscope (TEM), to evaluate the appearance of stromal and follicle cells as affected by different protein sources. Our data indicate that FCS is a better protein support for ovarian tissue cryopreservation when compared to SSS or Plasmanate. In addition the follicles are more resistant to the cryopreservation with respect to stroma.

Introduction We aimed to analyze the influence of intraoperative blood transfusion on postoperative complications and survival and to identify the preoperative variables associated with greater intraoperative bleeding. Materials and Methods Thirty-one elective liver transplantations (OLT) without blood transfusion performed between 1986 and 2002 (group 1) were compared with 62 patients (group 2) who underwent elective OLT with intraoperative transfusion after matching for gender, disease severity, and chronology. Results The hemoglobin and hematocrit values were significantly greater in group 1 compared to group 2. No significant differences were reported for the other parameters. In particular, the type of surgical technique had no influence on the blood requirement. As expected the nontransfused patients received less autologous packed red blood cells compared with the transfused patients. No differences were observed in either group for mean CIT, ICU and hospital stay, or acute rejection. A significant difference was observed in the number of postoperative infectious episodes, which was higher in group 2 (28 vs 5, P = .01). Graft and patient survivals at 3 months and 5 years did not differ significantly between groups. Conclusions OLT without blood transfusion may be achieved in the presence of good recipient conditions. Lower preoperative hemoglobin and hematocrit values were associated with greater intraoperative transfusions.

We present a review of the current literature on skin diseases in renal transplant recipients (RTR) and the results of a 5-year follow-up of 285 patients. Many skin diseases are only an aesthetic and functional cause for interest, but HPV infections and skin cancers are significantly more frequent in RTR than in immunocompetent subjects and can affect a patient's prognosis. For this reason, we feel dermatological surveillance of RTR is necessary for early diagnosis and treatment of all high-risk lesions.

Foot revascularization by popliteal-to-distal by-pass is a well documented procedure for limb salvage in diabetic patients. The authors report their experience with a consecutive series of 5 ischemic feet [transcutaneous oxygen (PtO2): 6 +/- 5.6 mmHg] due to extensive tibial artery occlusive disease beginning at the popliteal artery trifurcation. Limb salvage was achieved by popliteal-to-anterior tibial bypass (1 case) and popliteal-to-dorsalis pedis artery by-pass with autogenous inverted saphenous vein. No operative death was observed. At follow-up (range 3-34 months) one patient died at 3 months after surgery because of an intestinal bleeding. All 4 remaining by-passes are well functioning [PtcO2 46 +/- 11.2 mmHg) and all patients have resumed their normal walking distance. This preliminary experience, and a review of the literature, confirm the validity of the popliteal-to-distal by-pass and the need for more aggressive vascular surgical attitude to treat the ischemic diabetic foot.

The authors report a study in which they evaluate the efficacy of some laboratory parameters for monitoring intrasplenic hepatocyte xenotransplantation (mouse to rat) as an alternative to 99Tc-HIDA dynamic scan and histologic exam. Swiss mouse and wistar rat hepatocytes were obtained with collagenase digestion. Wistar male rats were used as recipient and were allocated into three groups: A) omotransplanted rats; B) xenotransplanted rats; C) xenotransplanted and immunosuppressed (Cyclosporin A: 20 mg/kg/daily orally) rats. All rats underwent > 70% hepatectomy. Blood samples were obtained daily from a femoral vein and AST, ALT, ALP, bilirubin, albumin and urea were measured. No statistical differences were observed among groups and the laboratory parameters tested can't be considered a valid technique to xenotransplant rejection monitoring.

In Genoa, 39 patients affected by disseminated neuroblastoma, one to twelve years old, were treated with intensive chemotherapy (Vincristine 4 mg/sqm c.i. over 5 days, Melphalan 140 mg/sqm), total body irradiation (TBI) (3.3 Gy for 3 days), and unpurged autologous bone marrow transplantation (ABMT) since October 1984 until November 1987. Thirty-two patients were in complete response (first group) and 7 had residual disease (second group) after an intensive chemotherapeutic induction regimen. Actuarial overall survival at 38 months is 52% and disease free survival at 30 months is 28% for the first group. Actuarial overall survival at 25 months is instead 14% for the second group related treatment toxicity has not been too high (3 deaths).