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BACKGROUND: Three-Dimensional (3D) printing technology can be used to manufacture training platforms for surgeons. Kidney transplantation offers a suitable model, since it mostly entails vascular and ureteric anastomoses. METHODS: A new simulation platform for surgical training in kidney transplantation was realized and validated in this study. A combination of different 3-D printing technology was used to reproduce the key anatomy of lower abdomen, of pelvis, and of a kidney graft, including their mechanical properties. RESULTS: Thirty transplantations were performed by two junior trainees with no previous experience in the area. Analysis of the times required to perform the simulated transplantation showed that proficiency was reached after about ten cases, as indicated by a flattening of the respective curves that corresponded to a shortening of about 40% and 47%, respectively, of the total time initially needed to perform the whole simulated transplantation. Although an objective assessment of the technical quality of the anastomoses failed to show a significant improvement throughout the study, a growth in self-confidence with the procedure was reported by both trainees. CONCLUSION: The quality of the presented simulation platform aimed at reproducing in the highest possible way a realistic model of the operative setting and proved effective in providing an integrated training environment where technical skills are enhanced together with a team-training experience. As a result the trainees' self-confidence with the procedure resulted enforced. Three-D--printed models can also offer pre-operative patient-specific training when anatomical variants are anticipated by medical imaging. An analysis of the costs related to the use of this platform is also provided and discussed.
Assuntos
Transplante de Rim , Treinamento por Simulação , Competência Clínica , Simulação por Computador , Humanos , Rim , Modelos Anatômicos , Impressão Tridimensional , Treinamento por Simulação/métodosRESUMO
Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long "no-touch period" and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.
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Oxigenação por Membrana Extracorpórea , Transplante de Rim , Obtenção de Tecidos e Órgãos , Morte Encefálica , Função Retardada do Enxerto , Oxigenação por Membrana Extracorpórea/métodos , Sobrevivência de Enxerto , Humanos , Rim/fisiologia , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.
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Seleção do Doador , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Transplante de Rim/métodos , Rim/anatomia & histologia , Doadores Vivos , Nefrectomia/métodos , Coleta de Tecidos e Órgãos/métodos , Feminino , Sobrevivência de Enxerto , Humanos , Rim/irrigação sanguínea , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.
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Infecções por Citomegalovirus , Citomegalovirus , Transplantados , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transplante de Órgãos/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Idoso , DNA Viral , Células Dendríticas/imunologia , ELISPOT , Testes Imunológicos/métodos , Citocinas/metabolismoRESUMO
BACKGROUND & OBJECTIVES: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. METHODS: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5 ± 11.8 yr) with transplant age 52.3 ± 34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. RESULTS: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment ( P ≤ 0.01) and/or calcineurin-inhibitors (CNI) exposure ( P ≤ 0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. INTERPRETATION & CONCLUSIONS: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment.
Assuntos
Falência Renal Crônica/complicações , Transplante de Rim/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/complicações , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Basiliximab , Daclizumabe , Feminino , Rejeição de Enxerto , Humanos , Imunoglobulina G/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/análogos & derivados , Micoses/induzido quimicamente , Micoses/complicações , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do Tratamento , Viroses/induzido quimicamente , Viroses/complicaçõesRESUMO
Since the identification of the new severe acute respiratory syndrome virus 2 (SARS-CoV-2), a huge effort in terms of diagnostic strategies has been deployed. To date, serological assays represent a valuable tool for the identification of recovered COVID-19 patients and for the monitoring of immune response elicited by vaccination. However, the role of T-cell response should be better clarified and simple and easy to perform assays should be routinely introduced. The main aim of this study was to compare a home-made assay for whole blood stimulation with a standardized ELISpot assay design in our laboratory for the assessment of spike-specific T-cell response in vaccinated subjects. Even if a good correlation between the assays was reported, a higher percentage of responder subjects was reported for immunocompromised subjects with ELISpot assay (56%) than home-made whole blood stimulation assay (33%). Additionally, three commercial assays were compared with our home-made assay, reporting a good agreement in terms of both positive and negative results.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely impacted on public health, mainly on immunosuppressed patients, including solid organ transplant recipients. Vaccination represents a valuable tool for the prevention of severe SARS-CoV-2 infection, and the immunogenicity of mRNA vaccines has been evaluated in transplanted patients. In this study, we investigated the role of a third dose of the BNT162b2 vaccine in a cohort of kidney transplant recipients, analyzing both humoral and cell-mediated responses. We observed an increased immune response after the third dose of the vaccine, especially in terms of Spike-specific T cell response. The level of seroconversion remained lower than 50% even after the administration of the third dose. Mycophenolate treatment, steroid administration and age seemed to be associated with a poor immune response. In our cohort, 11/45 patients experienced a SARS-CoV-2 infection after the third vaccine dose. HLA antibodies appearance was recorded in 7 out 45 (15.5%) patients, but none of the patients developed acute renal rejection. Further studies for the evaluation of long-term immune responses are still ongoing, and the impact of a fourth dose of the vaccine will be evaluated.
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BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
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Cardiomiopatias , Transplante de Coração , Síndrome MELAS , Doenças Musculares , Insuficiência Renal Crônica , Cardiomiopatias/complicações , Cardiomiopatias/genética , Cardiomiopatias/cirurgia , DNA Mitocondrial/genética , Humanos , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Síndrome MELAS/patologia , Mutação , Insuficiência Renal Crônica/complicaçõesAssuntos
Obstrução do Cateter , Cateteres de Demora , Deficiências do Desenvolvimento , Diálise Peritoneal Ambulatorial Contínua/instrumentação , Insuficiência Renal/terapia , Doenças Uterinas/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Doenças Uterinas/diagnóstico por imagem , Doenças Uterinas/cirurgiaRESUMO
BACKGROUND: Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. METHODS: This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from >60-year-old deceased donors. RESULTS: The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (p = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (>80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8-22.8 h; >24 h in 5 cases). The 6-month GFR was 41.2 (34.9-55.7) mL/min. Vascular resistances positively correlated with global histologic score (p = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (p < 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (p < 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (p = 0.009, r = -0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: -0.894, p = 0.005). CONCLUSIONS: MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.
Assuntos
Taxa de Filtração Glomerular , Transplante de Rim , Rim/anatomia & histologia , Perfusão/métodos , Doadores de Tecidos , Idoso , Cadáver , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
Background: Living donor kidney transplantation (LDKT) is the treatment of choice for end stage renal disease. LDKT involves complex psychosocial issues, which remain partially unexplored. Methods: The study involved all potential living donors and recipient pairs consecutively referred for psychosocial evaluation from the nephrologist. Clinical and sociodemographic variables including prior psychiatric history, previous and current use of psychopharmacological therapy, motivation and information about the transplant procedure were collected. Study participants completed the Symptom Checklist-90-R (SCL-90-R) to assess psychopathological distress. Results: Fifty-three donor/recipient pairs underwent psychiatric and psychological evaluation. Seven subjects (13%) in the recipient group and 13 subjects (25%) in the donor group reported a history of psychological distress and/or psychiatric conditions. A psychiatric diagnosis was confirmed in 4 recipients (7.5% of the study sample, including autism spectrum disorder, histrionic personality disorder, and anxiety-depressive disorders) and 5 donors (9%, including narcissistic personality disorder in one case and anxiety-depressive disorders). SCL-90-R GSI mean scores were 0.3 ±0.3 and 0.2 ±0.2 for the recipient and donor groups, respectively. Overall, 8 couples (15%) suspended the living donation pathway before transplantation. Four couples were excluded for a new onset medical condition. The psychological and psychiatric evaluation excluded one candidate. One couple dropped out before completing the scheduled exams. One recipient refused to undergo crossover renal transplantation, while 1 donor candidate withdrew her consent for transplantation at the end of the evaluation process. Conclusions: Limited but significant psychopathological distress in donors and recipients supports the usefulness of psychiatric and psychological competencies within the transplant team.
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Transtorno do Espectro Autista , Falência Renal Crônica , Transplante de Rim , Depressão , Feminino , Humanos , Falência Renal Crônica/cirurgia , Doadores VivosRESUMO
A promising way to increase the number of kidneys for transplantation is to expand the donor pool by including non-heart-beating donors (NHBDs). The centers involved in NHBD transplantation programs have reported a 16-40% increase in kidney transplants. A key issue with NHBD is the significantly higher rate of delayed graft function (DGF) and primary non-function (PNF) compared with that associated with heart-beating donor (HBD) transplants. However, although transplants from NHBD are associated with a greater incidence of early adverse events, long-term graft survival appears to be similar to that observed after transplants from HBDs. In addition, the use of extracorporeal membrane oxygenation and mechanical perfusion, the careful selection of recipients and donors, and an adequate therapeutic strategy may at least partially reduce the risk of PNF and DGF and improve transplant outcome.
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Parada Cardíaca , Transplante de Rim , Coleta de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos/métodos , Morte Encefálica , Função Retardada do Enxerto , Sobrevivência de Enxerto , Humanos , Itália , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Preservação de Órgãos/métodos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Myostatin (Mstn) has been described as a trigger for the progression of atherosclerosis. In this study, we evaluated the role of Mstn in arterial remodeling in patients with end-stage renal disease (ESRD). METHODS: Vascular specimens were collected from 16 ESRD patients (56.4±7.9 years) undergoing renal transplant (recipients) and 15 deceased kidney non-uremic donors (55.4±12.1 years). We studied gene and protein expression of Mstn, ubiquitin ligases, Atrogin-1, and muscle ring finger protein-1 (MuRF-1), inflammatory marker CCL2, cytoskeleton components, and Klotho by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Moreover, we assessed vascular calcification and collagen deposition. Finally, we studied the effects of recombinant Mstn on rat vascular smooth muscle cells (VSMCs, A7r5) and evaluated the effects of uremic serum (US) on primary human VSMCs. RESULTS: Myostatin mRNA was upregulated in the arterial vascular wall of recipients compared with donors (~15- folds, pï¼0.05). This response was accompanied by the upregulation of gene expression of Atrogin-1 and MuRF-1 (ï¼2.5- and ï¼10-fold) and CCL2 (ï¼3-fold). Conversely, we found downregulation of protein expression of Smoothelin, α-smooth muscle actin (α-SMA), vimentin, and Klotho (-85%, -50%, -70%, and -80%, respectively; pï¼0.05) and gene expression of vimentin and Klotho. Exposition of A7r5 to Mstn induced a time-dependent SMAD 2/SMAD 3 phosphorylation and expression of collagen-1 and transforming growth factor ß (TGFß) mRNA, while US induced overexpression of Mstn and Atrogin-1 and downregulation of Smoothelin and Klotho. CONCLUSIONS: Our data suggest that uremia might induce vascular Mstn gene expression together with a complex pathway of molecular and structural changes in the vascular wall. Myostatin, in turn, can translate the metabolic alterations of uremia into profibrotic and stiffness inducing signals.
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Artérias/patologia , Endotélio Vascular/patologia , Falência Renal Crônica/metabolismo , Miostatina/metabolismo , Adolescente , Adulto , Idoso , Animais , Quimiocina CCL2/biossíntese , Colágeno/metabolismo , Citoesqueleto/metabolismo , Feminino , Regulação da Expressão Gênica , Glucuronidase/biossíntese , Humanos , Inflamação , Falência Renal Crônica/fisiopatologia , Transplante de Rim , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Músculo Liso Vascular/metabolismo , Ratos , Proteínas Ligases SKP Culina F-Box/biossíntese , Proteínas com Motivo Tripartido/biossíntese , Ubiquitina-Proteína Ligases/biossíntese , Adulto JovemRESUMO
Donation after circulatory death (DCD) is a valuable option for the procurement of organs for transplantation. In Italy, organ procurement after controlled DCD is legally and ethically conceivable within the current legislative framework. However, although formal impediments do not exist, the health care team is faced with many obstacles that may hinder the implementation of such programs. We report the case of Italy's first controlled DCD, specifically discussing the role of the patient's family in the shared decision-making process. In our case, the death of the patient subsequent to the withdrawal of life-sustaining therapies was consistent with the patient's wishes, showing respect for his dignity and honoring his autonomy, as expressed to his family previously. By making donation possible, the medical team was able to fulfill the family's last request on behalf of the patient. This case should stimulate deliberation regarding the potential to shorten the 20-minute no-touch period currently in place in Italy. Such an action would not have injured this patient and would certainly have increased the quality of the procured organs.
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Morte , Tomada de Decisões , Obtenção de Tecidos e Órgãos , Cuidados Críticos , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
Donation after circulatory death (DCD) is a valuable option for the procurement of functioning organs for transplantation. Clinical results are promising and public acceptance is quite good in most western countries. Yet, although DCD is widespread in Europe, several problems still persist in Italy as well as in some other countries. This paper aims to describe the main clinical, organisational, ethical and legal issues at stake, bearing in mind the particular situation created by Italian legislation. Currently, as regards DCD, Italy is somewhat different from other countries. Therefore, every effort should be made for the safe and effective implementation of DCD programs: uncontrolled DCD programs should be promoted and encouraged, within the framework of shared and authoritative rules. At the same time, we need to tackle the question of controlled DCD, promoting debate among all involved subjects regarding the fundamental issues of end-of-life care within protocols that best integrate the highest standard of care for the dying and the legitimate interests of those awaiting a life-saving organ.
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Doadores de Tecidos/ética , Doadores de Tecidos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Atitude , Morte , Humanos , Itália , Assistência Terminal , Doadores de Tecidos/psicologiaRESUMO
Regulatory T cells (Tregs), defined as CD4+CD25+highFoxP3+CD127- cells, could promote tolerance in renal transplantation (Tx). In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2 years. The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes. There were no significant differences in either circulating or tissue Treg number between the two groups. At 1 month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69-) and for other immunocompetent cells (CD4+ and CD8+ T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss. Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens.
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Ciclosporina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Sirolimo/administração & dosagem , Linfócitos T Reguladores/efeitos dos fármacos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antígenos CD/metabolismo , Basiliximab , Proliferação de Células/efeitos dos fármacos , Ciclosporina/efeitos adversos , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão , Quimioterapia de Indução , Quimioterapia de Manutenção , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Sirolimo/efeitos adversos , Linfócitos T Reguladores/imunologia , Tolerância ao TransplanteRESUMO
Kidney transplantation is the only potentially curative treatment for patient facing end-stage renal disease, and it is now routinely used. Its use is mainly limited by the supply of transplantable donor organs, which far exceeds the demand. Regenerative medicine and tissue engineering offer promising means for overcoming this shortage. In the present study, we developed and validated a protocol for producing acellular rat renal scaffolds. Left kidneys were removed from 26 male Lewis rats (weights: 250-350 g) and decellularized by means of aortic anterograde perfusion with ionic and anionic detergents (Triton X-100 1% and SDS 1%, respectively). 19 scaffolds thus obtained (and contralateral native kidneys as controls) were deeply characterized in order to evaluate the decellularization quality, the preservation of extracellular matrix components and resultant micro-angioarchitecture structure. The other 7 were transplanted into 7 recipient rats that had undergone unilateral nephrectomy. Recipients were sacrificed on post-transplantation day 7 and the scaffolds subjected to histologic studies. The dual-detergent protocol showed, with only 5 h of perfusion per organ, to obtain thoroughly decellularized renal scaffolds consisting almost exclusively of extracellular matrix. Finally the macro- and the microarchitecture of the renal parenchyma were well preserved, and the grafts were implanted with ease. Seven days after transplant, the scaffolds were morphologically intact although all vascular structures were obstructed with thrombi. Production and implantation of acellular rat renal scaffolds is a suitable platform for further studies on regenerative medicine and tissue engineering.
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Matriz Extracelular/química , Matriz Extracelular/transplante , Rim/química , Rim/crescimento & desenvolvimento , Engenharia Tecidual/instrumentação , Alicerces Teciduais , Animais , Sistema Livre de Células , Análise de Falha de Equipamento , Rim/citologia , Masculino , Desenho de Prótese , Ratos , Ratos Endogâmicos LewRESUMO
Background & objectives: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. Methods: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5±11.8 yr) with transplant age 52.3±34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. Results: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment (P≤0.01) and/or calcineurin-inhibitors (CNI) exposure (P≤0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. Interpretation & conclusions: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment.