Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting further detailed exercise protocols and to fostering improved posttransplantation health and survival, helping to ensure that physical activity becomes a safe routine medical treatment plan of patient management.

Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

Focal C4d staining in peritubular capillaries and kidney graft survival: results of a retrospective study.

A diffuse positivity (>or=50%) of C4d in kidney graft peritubular capillaries (PTC) significantly correlates with the presence of acute or chronic antibody-mediated rejection. In contrast, significance of a "focal" deposit (10%-50%) is not yet completely defined. The purpose of this study was to assess the impact of focal positive C4d staining on graft survival. We retrospectively reviewed 63 renal biopsies in 54 kidney transplant recipients. They were performed between January 2005 and December 2008 because of graft impairement, namely, a significant increase in serum creatinine and/or urinary protein. C4d positivity was assessed by immunohistochemistry on paraffin-embedded sections, in combination with conventional histopathologic evaluation. Biopsies were classified as negative (<10%) versus with focal (10%-50%) or diffuse deposits (>50%). Cumulative survival was calculated by the Kaplan-Meier method, and Cox regression analysis was used for the multivariate analysis. Focal C4d staining in PTC significantly correlated with worse graft survival (P = .006), similarly to diffuse C4d staining. On multivariate analysis, focal C4d staining prognostically correlated with graft survival, but not recipient or donor age, prior transplantation, number of HLA mismatches or the presence of tubulitis in the sample. Focal C4d staining was associated with worse graft survival.

Bimodal distribution of major cardiovascular events in kidney allograft recipients.

Cardiovascular disease (CVD) is the major cause of death after renal transplantation. We have retrospectively analyzed the incidence and the time of appearance of CVD among 870 consecutive cadaveric kidney transplant recipients, including 143 patients (16.5%) who experienced a fatal or nonfatal event after transplantation. Seventy-four recipients (54%) showed a fatal CVD. Studying the various manifestations, we observed a higher frequency of cardiac events (59% of ischemic heart disease), with 15% cerebrovascular disease and 22% peripheral vascular or aortic disease. In our group, CVDs were distributed in a bimodal manner, with a higher incidence in the first posttransplantation year and a late cluster of CVD at 8 years posttransplantation. The risk of death (hazard function) for CVD increased dramatically during the 8th year after transplantation. This trend of CVD after kidney transplantation may be explained by inadequate evaluation and management of CVD risk factors during waiting list time and, after transplantation, by the cumulative effects of traditional and nontraditional risk factors.

Specific alloantigen self-control by regulatory T cells in organ transplantation: a review.

Multidrug immunosuppressive protocols have increased short-term patient and graft survival rates from 50% to 90% in the past two decades. Unfortunately, chronic graft rejection still remains the main cause of long-term failure and patients must undergo lifelong immunosuppression. The severe side effects such as life-threatening infections, secondary malignancies, and cardiovascular dysfunction all together include roughly 50% of deaths among kidney transplant patients with functioning grafts. Therefore, it should be of crucial importance to reduce immunosuppression and seek induction of specific tolerance to donor alloantigens. Several investigations have suggested that the acquisition of tolerance to self and/or foreign antigens is dependent on the number and function of naturally occurring and acquired regulatory T cells, which can control all aggressive T cells. The regulatory T cells together with their receptors, costimulatory molecules, cytokines, chemokines, and growth factors all contribute to maintain an equilibrium between aggressive and suppressive effector immune responses. As a consequence of increased knowledge, new immunosuppressive approaches based on either alloantigen-specific regulatory T-cell expansion in vivo or in vitro have been proposed to achieve donor-specific transplantation tolerance in kidney allograft recipients. This contribution attempted to summarize knowledge about regulatory T cells and developing methods to induce specific tolerance in kidney transplantation.

Monitoring of cellular immunity by interferon-gamma enzyme-linked immunosorbent spot assay in kidney allograft recipients: preliminary results of a longitudinal study.

Several efforts have been made in past years to identify markers for patients at heightened risk of acute and chronic immune-mediated allograft rejection. The ex vivo monitoring of cellular immunity by the enzyme-linked immunosorbent spot (ELISPOT) assay has recently emerged as a primary tool in predicting short- and long-term outcomes in kidney allograft recipients. Therefore, we started the systematic application of interferon-gamma (IFN-gamma) ELISPOT assay to measure the frequency of producing IFN-gamma in recipient peripheral blood lymphocytes (PBLs) stimulated with donor lymphocytes before and 7, 14, 21, 28, and 60 days after transplantation. Preliminary results in eight kidney transplant patients indicated that the number of HLA mismatches never correlated with the number of IFN-gamma spots. The frequencies of pretransplantation IFN-gamma spots were positively and significantly correlated with the number of posttransplantation IFN-gamma spots. Clinical outcomes were better among recipients with lower frequencies than those with higher frequencies of pre- and/or posttransplantation IFN-gamma spots. The highest pre- and posttransplantation number of IFN-gamma spots was observed in a patient who developed early acute rejection. Significant increases in the number of IFN-gamma spots preceded the onset of acute rejection events and were decreased by supplemental IV steroid administration. Considering the low number of observations, these preliminary results must be considered cautiously; nevertheless, we are encouraged to extend the systematic application of serial IFN-gamma ELISPOT assay measurements in a more consistent cohort of patients.

[Local recurrence of breast cancer]. / Le recidive locali nel carcinoma mammario.

The Authors analyse the prognostic value of the breast cancer local recurrence which not influence survival. For this reason the surgical treatment sometime can be conservative like the first treatment.

[Seminoma and adrenogenital syndrome]. / Seminoma e sindrome surrenogenitale.

The Authors report a case of a 26 year old patient affected by adrenogenital syndrome, likely due to 21 hydroxylase defect, hermaphroditism (46XX genotype and female phenotype) and worked hyperandrogenism; moreover a hidden testis neoplasm (seminoma) was associated.