RESUMO
INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.
Assuntos
Demência Frontotemporal , Predisposição Genética para Doença , Mutação/genética , Testes Neuropsicológicos/estatística & dados numéricos , Fatores Etários , Idoso , Encéfalo/patologia , Proteína C9orf72/genética , Feminino , Demência Frontotemporal/classificação , Demência Frontotemporal/genética , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Progranulinas/genética , Proteínas tau/genéticaRESUMO
BACKGROUND: The duration of anticytomegalovirus (CMV) prophylaxis after lung transplantation (LT) varies among transplant centers. METHODS: A retrospective review of CMV donor-seropositive/recipient-seronegative (D+/R-) and CMV recipient-seropositive (R+) LT patients between January 2005 and September 2012 was performed. Starting January 2007, valganciclovir prophylaxis was given for at least 12 months (often lifelong) for CMV D+/R- and extended from three to six months for R+ LT patients. Risks of CMV infection and CMV disease, and mortality after LT, were assessed. RESULTS: A total of 88 LT patients were studied, including 32 CMV D+/R-, and 56 R+ patients. During the follow-up period, 11 (12.5%) patients had asymptomatic CMV infection, and nine (10.3%) developed CMV disease. CMV disease (HR, 4.189; 95% CI: 1.672-10.495; p = 0.002) and CMV infection and disease (HR, 3.775; 95% CI: 1.729-8.240; p = 0.001) were significant risk factors for mortality. Overall, no significant difference was observed in rates of CMV infection or disease among LT recipients who received shorter vs. extended CMV prophylaxis. CONCLUSIONS: Despite extended prophylaxis, LT patients remain at risk of CMV infection and disease. CMV remains associated with increased mortality after transplantation.
Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/mortalidade , Citomegalovirus/efeitos dos fármacos , Ganciclovir/análogos & derivados , Rejeição de Enxerto/mortalidade , Pneumopatias/cirurgia , Transplante de Pulmão/mortalidade , Complicações Pós-Operatórias , Antibioticoprofilaxia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Ganciclovir/farmacologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , ValganciclovirRESUMO
This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Teste de Histocompatibilidade , Transplante de Rim , Troca Plasmática , Insuficiência Renal/cirurgia , Adulto , Anticorpos/química , Biópsia , Estudos de Coortes , Proteínas do Sistema Complemento/química , Feminino , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
Death with function (DWF) is a major cause of kidney allograft failure. Allograft dysfunction may contribute to DWF. The aim of this study was to examine the relationship between DWF and allograft function using estimated GFR (eGFR) and histology. We retrospectively analyzed 1842 kidney allografts transplanted at our center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies obtained 12 months posttransplant and within 1 year of DWF were analyzed. Proportional hazards models were used to examine the relationship between eGFR and DWF. During 68 ± 43 months of follow-up, 14% (n = 256) of recipients experienced DWF. Risk factors of DWF included increasing recipient age (hazard ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p = 0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated benign histology and were comparable to biopsies from matched controls. In conclusion, allograft dysfunction is independently associated with DWF. However, the majority of DWF recipients have well-preserved allograft function and histology prior to death.
Assuntos
Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/mortalidade , Adulto , Aloenxertos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/fisiologia , Humanos , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.
Assuntos
Biomarcadores/urina , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto/fisiologia , Nefropatias/urina , Transplante de Rim , Adulto , Albuminúria , alfa-Globulinas/urina , Creatinina/urina , Feminino , Rejeição de Enxerto/urina , Humanos , Imunoglobulina G/urina , Imunoglobulina M/urina , Nefropatias/patologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Peso Molecular , Prognóstico , Proteinúria , Proteínas Celulares de Ligação ao Retinol/urina , Microglobulina beta-2/urinaRESUMO
The effect of acute allograft rejection (AR) on long-term pancreas allograft function is unclear. We retrospectively studied 227 consecutive pancreas transplants performed at our institution between January 1, 998 and December 31, 2009 including: 56 simultaneous pancreas and kidney (SPK), 69 pancreas transplantation alone (PTA); and 102 pancreas after kidney (PAK) transplants. With a median follow-up of 6.1 (IQR 3-9) years, 57 patients developed 79 episodes of AR, and 19 experienced more than one episode. The cumulative incidence for AR was 14.7%, 19.7%, 26.6% and 29.1% at 1, 2, 5 and 10 years. PTA transplant (hazards ratio [HR]=2.28, p=0.001) and donor age (per 10 years) (HR=1.34, p=0.006) were associated with higher risk for AR. The first AR episode after 3 months post PT was associated with increased risk for complete loss (CL) (HR 3.79, p<0.001), and the first AR episode occurring during 3- to 12-month and 12- to 24-month periods after PT were associated with significantly increased risk for at least partial loss (PL) (HR 2.84, p=0.014; and HR 6.25, p<0.001, respectively). We conclude that AR is associated with increased risk for CL and at least PL. The time that the first AR is observed may influence subsequent graft failure.
Assuntos
Rejeição de Enxerto , Transplante de Pâncreas/métodos , Doença Aguda , Adolescente , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Nefropatias/mortalidade , Nefropatias/terapia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/mortalidade , Pancreatopatias/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 µg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 µg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
Assuntos
Ergocalciferóis/administração & dosagem , Hiperparatireoidismo Secundário/prevenção & controle , Transplante de Rim/efeitos adversos , Administração Oral , Conservadores da Densidade Óssea , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Estudos Prospectivos , Resultado do TratamentoRESUMO
This study assessed the development of allograft interstitial fibrosis and inflammation (GIF+"i"), a histologic pattern associated with reduced graft survival. Included are 795 adults, recipients of kidney allografts from 2000 to 2006. GIF+"i" was diagnosed in surveillance and clinical biopsies that had no transplant glomerulopathy. With time, posttransplant increasing number of grafts showed GIF+"i" and these patients had reduced death-censored graft survival (HR = 4.33 (2.49-7.53), p < 0.0001). Development of GIF+"i" was related to prior acute cellular rejection (ACR), BK nephropathy (PVAN), increasing number of HLA mismatches, retransplantation and DGF. However, 46.4% of GIF+"i" cases had no history of ACR or PVAN. Anti-HLA antibodies at transplant did not relate to GIF+"i" and these patients had no increased frequency of new antibody formation posttransplant. Post-ACR biopsies showed that GIF+"i" developed more commonly after clinically and/or histologically more severe ACR. Graft inflammation persisted in 38.7 and 29.6% of grafts 2 and 12 months post-ACR. Twelve months post-ACR, 27.1% of biopsies developed moderate-severe GIF and 51.8% showed GIF and inflammation. Persistent inflammation and progressive GIF is often subclinical but may lead to graft failure. GIF+"i" can be initiated by multiple etiologies but it is often postinfectious or due to persistent cellular immune-mediated injury.
Assuntos
Fibrose/etiologia , Rejeição de Enxerto/etiologia , Inflamação/etiologia , Transplante de Rim/efeitos adversos , Nefrite/etiologia , Adulto , Feminino , Fibrose/mortalidade , Fibrose/patologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Inflamação/mortalidade , Inflamação/patologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrite/mortalidade , Nefrite/patologia , Prognóstico , Taxa de Sobrevida , Transplante HomólogoRESUMO
BACKGROUND: The clinical features and outcome of prosthetic joint infection (PJI) among solid organ transplant (SOT) recipients have not been characterized. We performed a retrospective, matched case-control study to examine potential risk factors. METHODS: We reviewed cases of PJI among transplant recipients who were evaluated at the Mayo Clinic between 1989 and 2009. Cases were matched to non-infected controls based on transplant type, prosthetic joint type, and order of organ transplantation/joint implantation. RESULTS: Among 367 patients with both a joint prosthesis and an SOT, there were 12 cases of infection in those receiving immunosuppression. These occurred in 8 renal recipients, 3 liver recipients, and 1 heart transplant recipient. Six subjects had hip and 6 had knee arthroplasty infections. The observed time to prosthesis failure ranged from 0.5 to 148 months after implantation. Gram-positive bacteria (staphylococci and streptococci) caused the infection in 8 subjects. Two cases were caused by nontuberculous mycobacteria, whereas the remaining 2 cases were culture-negative in the setting of antimicrobial use. We did not find a statistically significant association between obesity, diabetes mellitus, or antimicrobial prophylaxis (given in the setting of immunosuppression) and development of PJI. A marginal association was seen between surgical site infection and the risk of PJI; however, this did not reach statistical significance. CONCLUSION: In our series, infection was mainly caused by gram-positive bacterial pathogens, similar to the commonly encountered organisms in the immunocompetent host, although opportunistic pathogens were also isolated.
Assuntos
Infecções por Bactérias Gram-Positivas/epidemiologia , Prótese Articular/microbiologia , Transplante de Órgãos/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição/efeitos adversos , Estudos de Casos e Controles , Feminino , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Articulação do Quadril/microbiologia , Humanos , Articulação do Joelho/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Isoanticorpos/sangue , Transplante de Rim , Adulto , Complemento C5/antagonistas & inibidores , Feminino , Rejeição de Enxerto/imunologia , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Troca PlasmáticaRESUMO
Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long-term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow-up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal-related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre-LT diabetes, post-LT diabetes, post-LT hypertension, post-LT renal insufficiency, retransplantation >1 year, pre-LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post-LT diabetes, hypertension and renal insufficiency were significant risk factors for liver-related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre-LT hypertension and post-LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post-LT factors including diabetes, hypertension and renal insufficiency may impact long-term mortality.
Assuntos
Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Alcoólicos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Feminino , Seguimentos , Hepatite C/induzido quimicamente , Hepatite C/etiologia , Hepatite C/mortalidade , Humanos , Hipertensão/induzido quimicamente , Hipertensão/etiologia , Hipertensão/mortalidade , Rim , Transplante de Rim/mortalidade , Fígado , Hepatopatias/etiologia , Hepatopatias/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Estudos Prospectivos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Fatores de Risco , Resultado do Tratamento , Estados UnidosRESUMO
Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (-XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and -XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of -XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates.
Assuntos
Nefropatias/diagnóstico , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Anticorpos/imunologia , Biópsia , Estudos de Coortes , Feminino , Rejeição de Enxerto , Teste de Histocompatibilidade/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
BACKGROUND: The Cogstate Brief Battery (CBB) is a computerized cognitive assessment that can be completed in clinic or at home. Design/Objective: This retrospective study investigated whether practice effects / performance trajectories of the CBB differ by location of administration. PARTICIPANTS/SETTING: Participants included 1439 cognitively unimpaired individuals age 50-75 at baseline participating in the Mayo Clinic Study of Aging (MCSA), a population-based study of cognitive aging. Sixty three percent of participants completed the CBB in clinic only and 37% completed CBB both in clinic and at home. MEASUREMENTS: The CBB consists of four subtests: Detection, Identification, One Card Learning, and One Back. Linear mixed effects models were used to evaluate performance trajectories in clinic and at home. RESULTS: Results demonstrated significant practice effects between sessions 1 to 2 for most CBB measures. Practice effects continued over subsequent testing sessions, to a lesser degree. Average practice effects/trajectories were similar for each location (home vs. clinic). One Card Learning and One Back accuracy performances were lower at home than in clinic, and this difference was large in magnitude for One Card Learning accuracy. Participants performed faster at home on Detection reaction time, although this difference was small in magnitude. CONCLUSIONS: Results suggest the location where the CBB is completed has an important impact on performance, particularly for One Card Learning accuracy, and there are practice effects across repeated sessions that are similar regardless of where testing is completed.
Assuntos
Instituições de Assistência Ambulatorial , Disfunção Cognitiva/diagnóstico , Testes de Estado Mental e Demência , Idoso , Envelhecimento , Feminino , Humanos , Internet , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 +/- 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes.
Assuntos
Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Transplante de Rim/estatística & dados numéricos , Doença Aguda , Atrofia/complicações , Feminino , Fibrose/complicações , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Homólogo/estatística & dados numéricosRESUMO
The incidence, risk factors and impact on patient and graft survival were evaluated for posttransplant lymphoproliferative disorder (PTLD) among 212 pancreas transplant recipients. Thirteen (6.1%) developed PTLD during 71 +/- 27 months follow-up. Cumulative incidences of PTLD at 1, 3, 5 and 10 years posttransplant were 4.2%, 5.3%, 6.0% and 7.0%, respectively. Incidence of PTLD was lower for recipients of simultaneous pancreas kidney compared to pancreas after kidney transplant or pancreas transplant alone, though not significantly so. Recipient Epstein-Barr virus (EBV) seronegativity and number of doses of depleting antibody therapy administered at transplant were associated with increased risk of PTLD, while recipient age, gender, transplant type, cytomegalovirus mismatch maintenance immunosuppression type and treated acute rejection were not. All 13 cases underwent immunosuppression reduction, and 10 received anti-CD20 monoclonal antibody. During follow-up, 10/13 (77%) responded to treatment with complete remission, while 3 (23%) died as a result of PTLD. Patient and graft survivals did not differ for recipients with and without PTLD. The strong association of PTLD with EBV-seronegativity requires considering this risk factor when evaluating and monitoring pancreas transplant recipients. With reduction of immunosuppression and anti-CD20 therapy, survival for pancreas transplant recipients with PTLD was substantially better than previously reported.
Assuntos
Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/epidemiologia , Transplante de Pâncreas/efeitos adversos , Adulto , Estudos de Coortes , Citomegalovirus/imunologia , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Incidência , Transtornos Linfoproliferativos/imunologia , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/imunologia , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The aim of this study was to assess the patterns, predictors and outcomes of left ventricular remodeling after heart transplantation (HTX). Routine echocardiographic studies were performed and analyzed at 1 week, 1 year and 3-5 years after HTX in 134 recipients. At each study point the total cohort was divided into three subgroups based on determination of left ventricle mass and relative wall thickness: (1) NG-normal geometry (2) CR-concentric remodeling and (3) CH-concentric hypertrophy. Abnormal left ventricular geometry was found as early as 1 week after HTX in 85% of patients. Explosive mode of donor brain death was the most significant determinant of CH (OR 2.9, p = 0.01) at 1 week. CH at 1 week (OR 2.72, p = 0.01), increased body mass index (OR 1.1, p = 0.01) and cytomegalovirus viremia (OR - 4.06, p = 0.02) were predictors of CH at 1 year. CH of the cardiac allograft at 1 year was associated with increased mortality as compared to NG (RR 1.87, p = 0.03). CR (RR 1.73, p = 0.027) and CH (RR 2.04, p = 0.008) of the cardiac allograft at 1 year is associated with increased subsequent graft arteriosclerosis as compared to NG.
Assuntos
Vasos Coronários/fisiopatologia , Transplante de Coração , Taxa de Sobrevida , Remodelação Ventricular , Adulto , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
BACKGROUND AND AIMS: Risk factors for mortality and re-bleeding following acute variceal haemorrhage (AVH) are incompletely understood. The aim of this study was to determine risk factors for 6-week mortality, and re-bleeding within 5 days in patients with cirrhosis and AVH. METHODS: Kaplan-Meier and Cox proportional hazards regression analyses were used to determine risk factors among 256 patients with AVH entered into a randomised, prospective trial. RESULTS: Thirty-five patients (14%) died within 6 weeks of AVH; 14 deaths (40%) occurred within 5 days. Only the Model for End-stage Liver Disease (MELD) score and units of packed red blood cells (PRBCs) transfused in the first 24 h were associated with 6-week mortality univariately (HR 1.11, p < 0.001; HR 1.22, p < 0.001) and bivariately (HR MELD = 1.10, p < 0.001; HR per unit of PRBCs transfused = 1.15, p = 0.005). Re-bleeding within 5 days occurred in 37 patients (15%); MELD score (p = 0.01) and a clot on a varix (p = 0.05) predicted re-bleeding. Patients with a MELD score > or = 18; both MELD score > or = 18 and > or = 4 units of PRBCs transfused; both MELD score > or = 18 and active bleeding at index endoscopy; and variceal re-bleeding had increased risk of death 6 weeks post-AVH (HR = 7.4, p < 0.001; 11.3, p < 0.001; 9.9, p < 0.001; 10.2, p < 0.001 respectively). CONCLUSIONS: Patients with AVH and MELD score > or = 18, requiring > or = 4 units of PRBCs within the first 24 h or with active bleeding at endoscopy are at increased risk of dying within 6 weeks. MELD score > or = 18 is also a strong predictor of variceal re-bleeding within the first 5 days.
Assuntos
Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Cirrose Hepática/complicações , Doença Aguda , Terapia Combinada , Métodos Epidemiológicos , Esofagoscopia , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/uso terapêutico , Prognóstico , Recidiva , Índice de Gravidade de Doença , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
Some patients do not achieve normoglycemia after an otherwise successful pancreas transplant. The aim of this study was to define the incidence and risk factors for the development of persistent diabetes mellitus after pancreas transplantation. We studied the outcomes of 144 pancreas transplants performed at our institution between January 2001 and December 2005. Diabetes mellitus was defined as the persistent need for pharmacologic treatment of diabetes mellitus despite evidence of allograft function. Data are expressed as median (25-75% inter-quartile range). Median follow-up was 39 months (IQR 26-55 months). During the follow-up period, 28 patients (19%) developed diabetes mellitus with a functioning allograft. Factors predicting hyperglycemia included: pretransplant insulin dose, BMI and acute rejection episodes (p < 0.0001, p = 0.0002 and p < 0.02, respectively). The median pretransplant hemoglobin A1c for patients developing diabetes was 8.3% (IQR 7.0-9.4%) compared to 6.2% (IQR 5.8-7.4%) at 2 years after transplant (p = 0.0069). In conclusion, persistent diabetes mellitus can occur despite the presence of a functioning pancreas allograft and is due to increased pretransplant BMI, high pretransplant insulin requirements and episodes of acute rejection.
Assuntos
Diabetes Mellitus/epidemiologia , Transplante de Pâncreas , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus/fisiopatologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/fisiopatologia , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias/fisiopatologiaRESUMO
Patients waiting for a kidney transplant have high mortality despite careful preselection. Herein, we assessed whether cardiac troponin T (cTnT) can help stratify risk in patients selected for kidney transplantation. cTnT levels were measured in all kidney transplant candidates but the results were not used for patient selection. Among 644 patients placed on the kidney waiting list from 9/2004 to 12/2006, 61% had elevated cTnT levels (>0.01 ng/mL). Higher levels related to diabetes, longer time on dialysis, history of cardiovascular disease and low serum albumin. High cTnT also related to cardiac anomalies, including left ventricular hypertrophy (LVH), wall motion abnormalities and stress-inducible ischemia by dobutamine echo (DSE). However, 54% of patients without these cardiac findings had elevated cTnT. Increasing cTnT levels were associated with reduced survival (HR = 1.729, CI (1.25-2.39), p = 0.01) independently of low serum albumin (0.449 (0.24-0.83), p = 0.011) and history of stroke (3.368 (1.47-7.73), p = 0.0004). The results of the DSE and/or coronary angiography did not relate significantly to survival. However, high cTnT identified patients with abnormal echo findings and poor survival. Wait listed patients with normal cTnT have excellent survival irrespective of other factors. In contrast, high cTnT levels are strongly predictive of poor survival in the kidney transplant waiting list.