Non-thyroidal illness syndrome in chronic diseases: role of irisin as modulator of antioxidants.

OBJECTIVE: Non-thyroidal-illness syndrome (NTIS) refers to condition found in chronic diseases that is an adaptive mechanism. However, oxidative stress is related to NTIS in a vicious circle, due to deiodinases alteration and negative effects of low T3 on antioxidant levels or activity. Muscle is one of the main targets of thyroid hormones and it can secrete a myokine named irisin, which is able to induce the browning of white adipose tissue, energy expenditure and protect against insulin resistance. Inconclusive data have been reported about irisin role in chronic diseases. Moreover, no correlation with antioxidants has been investigated. Therefore, we performed a case-control study with the primary endpoint to evaluate irisin levels in two models of NTIS, such as chronic heart failure (CHF) and chronic kidney disease (CKD) during haemodialytic treatment. The secondary endpoint was the correlation with total antioxidant capacity (TAC) to establish a possible role of irisin in the modulation of antioxidant systems. PATIENTS AND METHODS: Three groups of subjects were enrolled. Group A included CHF patients (n=18; aged 70.22 ± 2.78 ys; BMI ± 27.75 ± 1.28 kg/m2); Group B included CKD patients (n=29; aged 67.03 ± 2.64; BMI 24.53 ± 1.01); finally, 11 normal subjects (Group C) have been enrolled as controls. Irisin has been evaluated by ELISA method and Total Antioxidant Capacity (TAC) by spectrophotometric method. RESULTS: Irisin was significantly higher in Group B vs. A and C groups (Mean ± SEM: 20.18 ± 0.61 ng/ml vs. 2.77 ± 0.77 and 13.06 ± 0.56, respectively; p<0.05); a significant correlation between irisin and TAC was observed in group B. CONCLUSIONS: These preliminary data suggest a possible role of irisin in the modulation of antioxidants in two chronic syndromes with low T3 (i.e., CHF and CKD) with differential pattern in these two models studied. Further insights are needed to confirm this pilot study, which could be the basis for a longitudinal investigation, to assess a prognostic role of irisin with possible therapeutic implications.

The legislation on living organ donation in Western Europe: legal and ethical analysis and impact on clinical practice.

In Europe there are various directives on living organ donation (LOD) that are applied differently in member countries. The objectives of this study were as follows: (1) to identify the most relevant normative differences among the countries of Western Europe, and (2) to evaluate the evolution of LOD data in these countries. We performed comparative analysis of national legislations to identify the most significant common and different regulatory elements that were evaluated subsequently from an ethical-legal point of view. For data analysis on LOD, we used the EULOD database of donations in Europe. Relevant legislative differences emerged among European countries. Through legal and ethical analysis, it has possible to delineate two legal guidelines: on the one hand, based primarily on informed consent applying the principle of individual autonomy, and on the other hand, informed consent associated with legal and medical criteria. From 1992 to 2009, countries with standards based primarily on individual informed consent showed an increase in LOD from 5.5% to 25.3%, which was greater than those in countries that had additional legal requirements, namely, from 1.6% to 16.0.%. The distinct transpositions of the European Directives among singles countries related to LOD are based essentially only on the request for informed consent or for additional medical and legal requirements. The former practices which increases LOD, can facilitate "organ tourism."

Ethical evaluation of risks related to living donor transplantation programs.

The shortage of available cadaveric organs for transplantation and the growing demand has incresed live donation. To increase the number of transplantations from living donors, programs have been implemented to coordinate donations in direct or indirect form (cross-over, paired, and domino chain). Living donors with complex medical conditions are accepted by several transplantation programs. In this way, the number of transplants from living has exceeded that from cadaver donors in several European countries. No mortality has been reported in the case of lung, pancreas, or intestinal Living donations, but the perioperative complications range from 15% to 30% for pancreas and lung donors. In living kidney donors, the perioperative mortality is 3 per 10,000. Their frequency of end-stage renal disease does not exceed the United States rate for the general population. However, long-term follow-up studies of living donors for kidney transplantations have several limitations. The frequency of complications in live donor liver transplantation is 40%, of these, 48% are possibly life-threatening according to the Clavien classification. Residual disability, liver failure, or death has occurred in 1% of cases. The changes in live donor acceptance criteria raise ethical issues, in particular, the physician's role in evaluating and accepting the risks taken by the living donor. Some workers argue to set aside medical paternalism on behalf of the principle of donor autonomy. In this way the medical rule "primum non nocere" is overcome. Transplantation centers should reason beyond the shortage of organs and think in terms of the care for both donor and recipient.

Transplantation and mental retardation: what is the meaning of a discrimination?

The issue of transplantation for patients affected by mental retardation (MR) has been and continues to be a matter of discussion. The recent policy of the Veneto region, a highly populated area in northern Italy, indicates that patients with MR are not eligible for any transplant of solid organs, indicating intelligence quotient (IQ) <50 as absolute and IQ <70 as a relative exclusion criteria. In the present study, we review current conceptualizations of MR, along with the current knowledge on transplantation in this population. Finally, we will review the international guidelines on this matter and discuss the social, ethical and political significance of such policy, arguing that it discriminates persons affected by MR.

[Malnutrition in patients on chronic hemodialysis: prevalence, pathogenesis, and treatment]. / La malnutrizione nel paziente in emodialisi cronica: prevalenza, patogenesi, terapia.

Malnutrition is common in patients on hemodialysis and is a strong predicor of morbidity and mortality. Much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in hemodialysis patients as well as in recognizing the link between malnutrition and morbidity and mortality. Nevertheless, there is no consensus concerning its management. Conventional interventions such as nutritional counseling, oral nutritional supplements and intradialytic parenteral nutrition and novel preventive and therapeutic strategies such as appetite stimulants, growth hormone, androgenic anabolic steroids, and antiinflammatory drugs have been tested with contradictory and inconclusive results. Malnutrition still remains an important challenge for the nephrologist in the third millennium.

Gonadal function and immunosuppressive therapy after renal transplantation.

UNLABELLED: End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents. METHODS: Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * CI; n = 29). RESULTS: Testosterone was significantly lower in group II versus group I (3.12 +/- 1.23 versus 4.39 +/- 1.53 ng/mL; P < .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes. CONCLUSION: Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.

[Splenic artery rupture in pancreatic pseudocyst]. / Rottura di arteria splenica in pseudocisti pancreatica.

Hemorrhage is one of the most threatening complication of pancreatic pseudocyst. It results from erosion of adjacent vessels. Splenic, gastroduodenal, pancreaticoduodenal and middle colic vessels are predominantly involved. Hemorrhage may present different feature: intra and/or extraperitoneal collection, gastrointestinal bleeding. The authors report the rupture of splenic artery into pseudocyst, with the formation of pulsating pseudoaneurysm, increasing progressively until the final rupture. For the diagnosis the authors utilized: ultrasounds (US) which showed the cyst but not its nature and content; the CT scan which disclosed haematic contents; finally the US Color Doppler which proved the dynamic feature of hemorrhage. This technique allows to identify the arterious or venous source of bleeding and the possible presence of arteriovenous fistula. Arteriography was not performed due to circumstances, although it would permit bleeding vessel embolization and the control of hemorrhage. This procedure is not ever achievable, and doesn't exclude the possibility of rebleeding. On surgery, since the intraoperative rupture of the pseudoaneurysm occurred with severe hypovolemic shock, only a timely posterior mesogastric mobilization and the medially displacement of spleen-body-tail pancreatic complex, allowed to clamp the mass and the hemostasis. When such lesion are approached, it is mandatory to be prepared to carry on this maneuver: the severity of bleeding cannot allow intracystic ligature of bleeding vessel.

Kaposi's sarcoma in renal-transplant recipients: experience at the Catholic University in Rome, 1988-1996.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) in patients transplanted at the Organ Transplant Center of Catholic University in Rome appears to have increased in recent years. OBJECTIVE: To describe the clinical characteristics of KS in a group of transplant recipients. METHODS: Over 8 years, a total of 302 renal-transplant recipients were followed. When KS was suspected, histology and staging procedures were performed. RESULTS: Ten cases of KS have been diagnosed (8 males, 2 females; age 46.4 +/- 9.4 years); 4 of them were on triple therapy. All the patients were HIV-1 seronegative. The onset of KS occurred 3 months to 4 years after transplantation (21.1 +/- 17.6 months). The disease was limited to the skin in 6 cases and involved internal organs in the remaining 4. Four patients experienced complete remission of the disease following reduction of the immunosuppressive therapy. CONCLUSION: The high incidence of KS in this population (2.98%), as compared to that reported in other transplant patient groups, suggests that, besides viral infection, genetic predisposition may play a pathogenetic role. However, immunosuppression is the leading factor in transplant patients.