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INTRODUCTION AND OBJECTIVE: The implementation of Enhanced Recover After Surgery (ERAS) multimodal rehabilitation protocols in radical cystectomy has shown to improve outcomes in hospital stay and complications. The aim of this analysis is to evaluate the impact of laparoscopic surgery on radical cystectomy within a multimodal rehabilitation program. MATERIAL AND METHODS: The study was carried out in a third level center between 2011 and 2020 including patients with bladder cancer submitted to radical cystectomy according to an ERAS (Enhanced Recovery After Surgery) protocol and the Spanish Multimodal Rehabilitation Group (GERM) with 20 items to be fulfilled. RESULTS: A total of 250 radical cystectomies were performed throughout the study period, 42.8% by open surgery (OS) and 57.2% by laparoscopic surgery (LS). The groups are comparable in demographic and clinical variables (pâ¯>â¯0.05). Operative time was longer in the LS group (248.4⯱â¯55.0 vs. 286.2⯱â¯51.9â¯min; pâ¯<â¯0.001). However, bleeding was significantly lower in the LS group (417.5⯱â¯365.7 vs. 877.9⯱â¯529.7 cc; pâ¯<â¯0.001), as was the need for blood transfusion (33.6% vs. 58.9%; pâ¯<â¯0.001). Postoperative length of stay (11.5⯱â¯10.5 vs. 20.1⯱â¯17.2 days; pâ¯<â¯0.001), total and major complications were also significantly lower in this group (LS). The readmission rate was lower in the LS group but not significantly (36.4% vs. 29.4%; pâ¯=â¯0.237). The difference between 90-day mortality in both groups was not statistically significant (2.8% LS vs. 4.3% OS; pâ¯=â¯0.546). The differences were maintained in the multivariate models. CONCLUSIONS: Laparoscopic surgery within a multimodal rehabilitation program increases operative time but significantly decreases intraoperative bleeding, transfusion requirements, postoperative length of stay, and complications.
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Cistectomia , Laparoscopia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/reabilitação , Cistectomia/métodos , Masculino , Laparoscopia/reabilitação , Feminino , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/reabilitação , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Recuperação Pós-Cirúrgica Melhorada , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Protocolos Clínicos , Tempo de Internação/estatística & dados numéricos , Terapia CombinadaRESUMO
BACKGROUND AND OBJECTIVE: Sunflower seed is one of the most common edible seeds and its consumption is growing. Case reports of sunflower seed allergy have been described since the 1970s. However, there are few data on the prevalence and clinical manifestations of sunflower seed allergy. To improve understanding of sunflower seed allergy. METHODS: We evaluated the clinical and immunological features of patients with sunflower seed allergy diagnosed in the Allergy Department of a tertiary hospital in Madrid over a 5-years period. RESULTS: Forty-seven patients reported adverse reactions after ingestion of sunflower seed and had specific sensitization to sunflower seed determined by skin prick test (median 8 mm) or specific IgE (median 1.10 kUA/L). Most had an adult-onset reaction to sunflower seed preceded by a history of atopy and other food allergies, predominantly to peach, peanut and nuts. Clinical presentation of sunflower seed allergy ranged from mild to severe, with a high proportion of patients suffering severe reactions, often undertreated. A variability in the severity of symptoms was seen on repeated exposures to sunflower seed on a same patient. Levels of sunflower seed IgE were strongly correlated with levels of IgE to non-specific lipid transfer proteins, while no significant differences were found in the severity of the reactions according to sensitization to those proteins. CONCLUSION: Our findings reveal a variability of clinical presentations of sunflower seed allergy on repeated exposures and an underuse of epinephrine in anaphylaxis. We highlight the importance of strict avoidance of sunflower seed and accurate prescription and administration of epinephrine in allergic patients.
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We report a case of complex bladder diverticulum causing lower urinary tract symptoms and obstructive uropathy with acute kidney injury. The diagnosis is usually based on clinical and imaging findings. Laparoscopic diverticulectomy and transurethral prostate resection were performed with good functional outcomes. We report a case of a large complex bladder diverticulum presenting as obstructive uropathy with voiding symptoms.
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INTRODUCTION AND OBJECTIVE: Rezum® system is a minimally invasive transurethral therapy that uses convective water vapor energy to ablate prostatic tissue. The objective is to report 1-year functional and security outcomes obtained by using this technique in real clinical practice. MATERIAL AND METHODS: Prospective study conducted in 5 Spanish hospitals for the treatment of LUTS secondary to BPH using the Rezum® system. Patients with prostatic medium lobe (ML) and urethral catheter carriers were also included. Pre- and post-operative data were collected using IPSS, IIEF-5 and QoL questionnaires, flowmetry and post-void residual volume. Complications and retreatment rate at one-year follow-up were also reported. RESULTS: 137 patients, including 64 with ML and 10 patients with urinary retention were treated. Median prostate volume was 50â¯cm3 (15-131). At 3 months follow-up, significant improvement was observed in IPSS (-6.37 points), Qmax (+4.95â¯mL/s) and QoL (-1.29); and was maintained until 12 months: -10.78 points, +4.62â¯mL/s and -2.73 respectively (pâ¯<â¯0.001). No significant changes were observed in the sexual sphere. All complications were mild (≤ Clavien II). Retreatment rate at one year was 4%. CONCLUSION: Short-term results of this technique are promising, showing improvement in terms of functional outcomes, with no impact on the sexual sphere or complications. Longer term follow-up should include treatment durability and comparison to standard BPH treatments.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Sintomas do Trato Urinário Inferior/cirurgia , Sintomas do Trato Urinário Inferior/terapia , Masculino , Estudos Prospectivos , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/terapia , Qualidade de Vida , Vapor , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the main factors involved in asthma control and health-related quality of life in elderly asthmatic patients. METHODS: We performed a retrospective case-control study nested in a historical cohort that compared patients who had partly controlled or uncontrolled asthma (Asthma Control Test [ACT] score ≤19) (cases) with patients who had well-controlled asthma (ACT ≥20) (controls). Clinical data were collected from medical records. Outcomes included ACT score and health-related quality of life (Asthma-Specific Quality of Life Questionnaire [AQLQ]). Pulmonary function was determined by spirometry. RESULTS: We evaluated 209 asthma patients (151 women) aged ≥65 years. Mean age was 73.55 years. Most patients had persistent moderate (47.60%) or severe (47.12%) asthma. A total ACT score ≤19 was obtained in 64 (30.62%) patients. Lack of adherence to treatment and presence of severe exacerbations were risk factors for partly controlled/uncontrolled asthma (OR, 8.33 and 5.29, respectively). In addition, for each additional unit score in the AQLQ, the risk of poor control increased by 1.51. The factors influencing the AQLQ score were asthma control (ACT) and presence of comorbidities such as depression, gastroesophageal reflux disease, and osteoporosis. CONCLUSIONS: Despite receiving antiasthma therapy, almost one-third of elderly patients had uncontrolled asthma, possibly as a result of poor adherence, exacerbations, and reduced health-related quality of life. Nonrespiratory comorbid conditions in older patients do not seem to be associated with worse control of asthma symptoms, although their effect on health-related quality of life could indirectly affect asthma control.
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Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Depressão/epidemiologia , Cooperação e Adesão ao Tratamento , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Comorbidade , Progressão da Doença , Feminino , Humanos , Masculino , Qualidade de Vida , Fatores de Risco , Espanha/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: White root rot disease caused by Rosellinia necatrix is one of the most important threats affecting avocado productivity in tropical and subtropical climates. Control of this disease is complex and nowadays, lies in the use of physical and chemical methods, although none have proven to be fully effective. Detailed understanding of the molecular mechanisms underlying white root rot disease has the potential of aiding future developments in disease resistance and management. In this regard, this study used RNA-Seq technology to compare the transcriptomic profiles of R. necatrix during infection of susceptible avocado 'Dusa' roots with that obtained from the fungus cultured in rich medium. RESULTS: The transcriptomes from three biological replicates of R. necatrix colonizing avocado roots (RGA) and R. necatrix growing on potato dextrose agar media (RGPDA) were analyzed using Illumina sequencing. A total of 12,104 transcripts were obtained, among which 1937 were differentially expressed genes (DEG), 137 exclusively expressed in RGA and 160 in RGPDA. During the root infection process, genes involved in the production of fungal toxins, detoxification and transport of toxic compounds, hormone biosynthesis, gene silencing and plant cell wall degradation were overexpressed. Interestingly, 24 out of the 137 contigs expressed only during R. necatrix growth on avocado roots, were predicted as candidate effector proteins (CEP) with a probability above 60%. The PHI (Pathogen Host Interaction) database revealed that three of the R. necatrix CEP showed homology with previously annotated effectors, already proven experimentally via pathogen-host interaction. CONCLUSIONS: The analysis of the full-length transcriptome of R. necatrix during the infection process is suggesting that the success of this fungus to infect roots of diverse crops might be attributed to the production of different compounds which, singly or in combination, interfere with defense or signaling mechanisms shared among distinct plant families. The transcriptome analysis of R. necatrix during the infection process provides useful information and facilitates further research to a more in -depth understanding of the biology and virulence of this emergent pathogen. In turn, this will make possible to evolve novel strategies for white root rot management in avocado.
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Perfilação da Expressão Gênica , Predisposição Genética para Doença/genética , Persea/microbiologia , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Xylariales/genética , Xylariales/fisiologia , Anotação de Sequência Molecular , RNA-SeqRESUMO
Many pediatric centers utilize a variety of protocols including preemptive plasmapheresis to prevent the recurrence of FSGS post-transplant. But the effectiveness of this expensive, time-consuming process of plasmapheresis in the prevention of FSGS recurrence is still unclear. We retrospectively reviewed all pediatric cases of FSGS in our center that received a kidney transplant and compared the transplant and patient outcomes of those transplanted after 2006 who received pretransplant plasmapheresis to those prior to 2006 who did not. Of the 57 children with FSGS, 31 and 26 were transplanted before and after 2006, respectively. The cohorts differed significantly in keeping with the center immunosuppression protocol changes, and prior to 2006, the recipients were significantly younger. All children with FSGS transplanted after 2006 underwent three and one sessions of 1.0 plasma volume/exchange plasmapheresis with fresh frozen plasma replacement prior to the transplant in living and deceased donors, respectively, in addition to five sessions of every other day post-transplant pheresis. The incidence (27% vs 26%, P = 1.0) and time to recurrence of FSGS in the kidney allograft (P = .22) were not significantly different in patients that did and did not undergo prophylactic plasmapheresis. We need to re-evaluate the role of preemptive plasmapheresis in the prevention of FSGS recurrence in a prospective multicenter study.
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Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim , Assistência Perioperatória/métodos , Plasmaferese/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. It is common for European Americans (EA) to carry two CYP3A5 loss-of-function (LoF) variants that profoundly reduces TAC metabolism. Despite having two LoF alleles, there is still considerable variability in TAC troughs and identifying additional variants in genes outside of the CYP3A5 gene could provide insight into this variability. We analyzed TAC trough concentrations in 1345 adult EA recipients with two CYP3A5 LoF alleles in a genome-wide association study. Only CYP3A4*22 was identified and no additional variants were genome-wide significant. Additional high allele frequency genetic variants with strong genetic effects associated with TAC trough variability are unlikely to be associated with TAC variation in the EA population. These data suggest that low allele frequency variants, identified by DNA sequencing, should be evaluated and may identify additional variants that contribute to TAC pharmacokinetic variability.
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Citocromo P-450 CYP3A/genética , Estudo de Associação Genômica Ampla , Transplante de Rim , Tacrolimo/farmacocinética , Adulto , Feminino , Frequência do Gene , Genótipo , Rejeição de Enxerto/sangue , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Tacrolimo/sangue , Tacrolimo/uso terapêutico , Transplantados , População Branca/genéticaRESUMO
Whether diabetes after kidney donation is associated with an accelerated GFR decay in the remaining kidney has not been studied. We determined the incidence of diabetes in kidney donors, and compared GFR change over time in diabetic to nondiabetic donors, in addition to the effect of diabetes mellitus (DM) on the development of proteinuria, hypertension, and end-stage renal disease (ESRD). Of the 4014 donors, 309 (7.7%) developed diabetes at a median age of 56.0 years and after a median of 18 years after donation. The difference in annual estimated GFR (eGFR) change between diabetic and nondiabetic donors in the 7 years before the development of DM was -0.08 mL/min/year; p = 0.51. After DM development, the difference was -1.10 mL/min/year for diabetic donors with hypertension and proteinuria, p < 0.001; -0.19 for diabetic donors with hypertension but no proteinuria, p = 0.29; -0.75 mL/min/year for diabetic donors with proteinuria but no hypertension, p = 0.19; and -0.09 mL/min/year for diabetic donors without proteinuria or hypertension, p = 0.63. When DM was considered as a time-dependent covariate, it was associated with the development of proteinuria (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.89-3.70; p < 0.001) and hypertension (HR 2.19, 95% CI 1.74-2.75; p < 0.001). It was not, however, associated with ESRD. eGFR decline after DM development exceeds that of nondiabetic donors only in diabetic donors with concomitant proteinuria and hypertension.
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Diabetes Mellitus/etiologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Doadores Vivos , Nefrectomia/efeitos adversos , Proteinúria/etiologia , Coleta de Tecidos e Órgãos/métodos , Adulto , Estudos de Casos e Controles , Diabetes Mellitus/patologia , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Incidência , Testes de Função Renal , Transplante de Rim , Masculino , Prognóstico , Proteinúria/patologia , Fatores de RiscoRESUMO
We previously demonstrated that detectable BKV replication in donor urine pretransplant was significantly associated with post-transplant recipient BKV viremia. In this 4-year prospective study, we assessed whether recipient BKV replication pretransplant was associated with post-transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person-years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and two children; and viremia in none pretransplant. Post-transplant viruria occurred in all recipients with pretransplant BKV viruria, significantly more than in recipients without pretransplant viruria on univariate (P<.005) and multivariate analysis including type of organ transplanted and immunosuppression type (P .008). Time to post-transplant viruria was significantly shorter in recipients with pretransplant viruria (P .01). By univariate and multivariate analysis, BKV viruria in recipients pretransplant did not impact post-transplant BKV viremia (P=.97 and .97, respectively) even when stratified by type of organ transplant (kidney P=.6; liver P=.5). The peak serum and urine BKV PCR post-transplant were not significantly different in patients with pretransplant BKV viruria and no one developed BK nephropathy. In conclusion, recipient BKV viruria prior to transplant predicts post-transplant viruria but not viremia or BKV nephropathy.
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Vírus BK/isolamento & purificação , Nefropatias/virologia , Transplante de Órgãos , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Seguimentos , Humanos , Lactente , Nefropatias/diagnóstico , Nefropatias/metabolismo , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/metabolismo , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/metabolismo , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/metabolismo , Viremia/diagnóstico , Viremia/metabolismo , Eliminação de Partículas Virais , Adulto JovemRESUMO
In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.
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Doadores Vivos , Transplante de Órgãos , Sistema de Registros , Obtenção de Tecidos e Órgãos , Atenção à Saúde , HumanosRESUMO
In small children with end-stage renal disease, an adult-sized kidney transplant is the best option. However, in the face of a completely thrombosed inferior vena cava (IVC), such transplants can be challenging, given the difficulty of achieving adequate renal venous outflow and the risk of graft thrombosis. Using a new technique to anastomose the renal vein to the right hepatic vein/IVC junction, we successfully implanted an adult-sized graft in two small children (9.8 and 14 kg) who had end-stage renal disease and a completely thrombosed IVC. After mobilizing the right lobe of the liver and obtaining total vascular occlusion of the liver, we used a Fogarty catheter to dilate the retrohepatic IVC. In the right hepatic vein, we made a venotomy and extended it inferiorly onto the retrohepatic IVC. To that venotomy, we anastomosed the donor left renal vein, using continuous 7-0 Prolene sutures. Both patients attained excellent renal allograft function: One had a serum creatinine level of 0.30 mg/dL at 6 mo after transplant, and the other had a level of 0.29 mg/dL at 1 year. In these two small children with completely thrombosed IVC, our technique for transplanting an adult-sized kidney provided adequate venous outflow.
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Transplante de Rim , Veia Cava Inferior/cirurgia , Trombose Venosa/cirurgia , Adulto , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Doadores Vivos , Masculino , PrognósticoRESUMO
Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5*3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5*6 and CYP3A5*7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5*1, *3, *6 and *7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy.
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Negro ou Afro-Americano/genética , Inibidores de Calcineurina/administração & dosagem , Citocromo P-450 CYP3A/genética , Cálculos da Dosagem de Medicamento , Imunossupressores/administração & dosagem , Transplante de Rim , Variantes Farmacogenômicos , Tacrolimo/administração & dosagem , Transplantados , Adolescente , Adulto , Idoso , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Canadá/epidemiologia , Citocromo P-450 CYP3A/metabolismo , Feminino , Frequência do Gene , Genótipo , Rejeição de Enxerto/etnologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Masculino , Taxa de Depuração Metabólica/genética , Pessoa de Meia-Idade , Modelos Genéticos , Farmacogenética , Testes Farmacogenômicos , Fenótipo , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non-end-stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non-ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less-than-ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.
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Nefropatias/etiologia , Transplante de Rim/métodos , Doadores Vivos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias , Coleta de Tecidos e Órgãos/efeitos adversos , Humanos , Fatores de RiscoRESUMO
The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship. Measures of surgical performance included intraoperative time, estimated blood loss, and incidence of intraoperative complications. The performance of senior TSFs was used to benchmark novice TSF performance. Scores were tabulated in a learning curve model, adjusting for case complexity and prior TSF case volume. Rates of adverse surgical events were significantly higher for novice TSFs than for senior TSFs. In univariable analysis, multiple renal arteries, high BMI, prior abdominal surgery, male donor, and nephrolithiasis were correlated with higher incidence of adverse surgical events. Based on the RACUSUM model, high intraoperative time is mitigated after 28 procedures, incidence of intraoperative complications tends to diminish after 24 procedures, and improvement in estimated blood loss did not remain consistent. TSFs exhibit a tipping point in LDN performance by 24-28 cases and proficiency by 35-38 cases.
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Cirurgia Geral/educação , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Laparoscopia/métodos , Doadores Vivos , Nefrectomia/métodos , Coleta de Tecidos e Órgãos/métodos , Bolsas de Estudo , Feminino , Seguimentos , Humanos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
In the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors (BENEFIT-EXT), extended criteria donor kidney recipients were randomized to receive belatacept-based (more intense [MI] or less intense [LI]) or cyclosporine-based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent-to-treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI-treated, 138 of 175 belatacept LI-treated and 108 of 184 cyclosporine-treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625-1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634-1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 mL/min per 1.73 m2 for belatacept MI, belatacept LI and cyclosporine, respectively (p < 0.001 for overall treatment effect). HRs comparing freedom from death, graft loss or eGFR <20 mL/min per 1.73 m2 were 0.754 (95% CI 0.536-1.061; p = 0.10) for belatacept MI versus cyclosporine and 0.706 (95% CI 0.499-0.998; p = 0.05) for belatacept LI versus cyclosporine. Acute rejection rates and safety profiles of belatacept- and cyclosporine-based treatment were similar. De novo donor-specific antibody incidence was lower for belatacept (p ≤ 0.0001). Relative to cyclosporine, belatacept was associated with similar death and graft loss and improved renal function at 7 years after transplant and had a safety profile consistent with previous reports.
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Abatacepte/uso terapêutico , Ciclosporina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
In the United States, live organ donation can be a costly and burdensome undertaking for donors. While most donation-related medical expenses are covered, many donors still face lost wages, travel expenses, incidentals, and potential for future insurability problems. Despite widespread consensus that live donors (LD) should not be responsible for the costs associated with donation, little has changed to alleviate financial burdens for LDs in the last decade. To achieve this goal, the transplant community must actively pursue strategies and policies to eliminate unreimbursed out-of-pocket costs to LDs. Costs should be more appropriately distributed across all stakeholders; this will also make live donation possible for people who, in the current system, cannot afford to proceed. We propose the goal of LD "financial neutrality," offer an operational definition to include the coverage/reimbursement of all medical, travel, and lodging costs, along with lost wages, related to the act of donating an organ, and guidance for consideration of medical care coverage, and wage and other expense reimbursement. The intent of this report is to provide a foundation to inform discussion within the transplant community and to advance initiatives for policy and resource allocation.
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Implementação de Plano de Saúde , Doadores Vivos , Nefrectomia/economia , Transplante de Órgãos/economia , Transplante de Órgãos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/economia , Análise Custo-Benefício , Gastos em Saúde , Política de Saúde , Humanos , Cobertura do Seguro/economia , Meios de Transporte/economia , Estados UnidosRESUMO
We previously reported that tacrolimus (TAC) trough blood concentrations for African American (AA) kidney allograft recipients were lower than those observed in white patients. Subtherapeutic TAC troughs may be associated with acute rejection (AR) and AR-associated allograft failure. This variation in TAC troughs is due, in part, to differences in the frequency of the cytochrome P450 CYP3A5*3 allele (rs776746, expresses nonfunctional enzyme) between white and AA recipients; however, even after accounting for this variant, variability in AA-associated troughs is significant. We conducted a genomewide association study of TAC troughs in AA kidney allograft recipients to search for additional genetic variation. We identified two additional CYP3A5 variants in AA recipients independently associated with TAC troughs: CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343). All three variants and clinical factors account for 53.9% of the observed variance in troughs, with 19.8% of the variance coming from demographic and clinical factors including recipient age, glomerular filtration rate, anticytomegalovirus drug use, simultaneous pancreas-kidney transplant and antibody induction. There was no evidence of common genetic variants in AA recipients significantly influencing TAC troughs aside from the CYP3A gene. These results reveal that additional and possibly rare functional variants exist that account for the additional variation.
Assuntos
Negro ou Afro-Americano/genética , Citocromo P-450 CYP3A/genética , Estudo de Associação Genômica Ampla , Rejeição de Enxerto/genética , Polimorfismo de Nucleotídeo Único/genética , Complicações Pós-Operatórias/genética , Tacrolimo/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Taxa de Filtração Glomerular , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etnologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Falência Renal Crônica/genética , Falência Renal Crônica/cirurgia , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Doadores de Tecidos , Transplantados , População Branca/genética , Adulto JovemRESUMO
Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH) is involved in the activation of neuroanatomical systems that are also associated with the processing of natural and other artificial rewarding stimuli. Specific components of this behavior (hedonic impact, learning, and motor behavior) may involve changes in different neurotransmitters, such as dopamine and opioids. In this study, quantitative autoradiography was used to examine changes in mu-opioid and D1/D2-dopamine receptor expression in various anatomical regions related to the motor and mesolimbic reward systems after intracranial self-stimulation of the LH. Results of the behavioral procedure and subsequent radiochemical assays show selective changes in D1 but not D2 or mu receptors in Accumbens-Shell, Ventral Pallidum, Caudate-Putamen, and Medial Globus Pallidus. These findings are discussed in relation to the different psychobiological components of the appetitive motivational system, identifying some dissociation among them, particularly with respect to the involvement of the D1-dopamine subsystem (but not D2 or mu receptors) in goal-directed behaviors.
Assuntos
Encéfalo/fisiologia , Região Hipotalâmica Lateral/fisiologia , Sistema Límbico/fisiologia , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Opioides mu/metabolismo , Animais , Autorradiografia , Encéfalo/metabolismo , Estimulação Elétrica , Sistema Límbico/metabolismo , Masculino , Ratos Wistar , AutoestimulaçãoRESUMO
Predicting long-term outcomes in renal transplant recipients is essential to optimize medical therapy and determine the frequency of posttransplant histologic and serologic monitoring. Nonadherence and human leukocyte antigen (HLA) mismatch are risk factors that have been associated with poor long-term outcomes and may help individualize care. In the present study, class II HLA mismatches were determined at the HLA epitope level in 195 renal transplant recipients in whom medication adherence was prospectively measured using electronic monitors in medication vial caps. Recipients were grouped by medication adherence and high (≥10 HLA-DR, ≥17 HLA-DQ) or low epitope-mismatch load. We found that the combination of higher epitope mismatch and poor adherence acted synergistically to determine the risk of rejection or graft loss. Nonadherent recipients with HLA-DR epitope mismatch ≥10 had increased graft loss (35% vs. 8%, p < 0.01) compared to adherent recipients with low epitope mismatch. At the HLA-DQ locus nonadherent recipients with HLA-DQ epitope mismatch ≥17 had increased graft loss (33% vs. 10%, p < 0.01) compared to adherent recipients with low epitope mismatch. Subclinical nonadherence early posttransplant combined with HLA class II epitope mismatch may help identify recipients that could benefit from increased clinical, histologic, and serologic monitoring.