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1.
N Engl J Med ; 389(21): 1972-1978, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37991855

RESUMO

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.


Assuntos
Doenças Genéticas Inatas , Glucagon , Hipertensão Portal , Transplante de Fígado , Feminino , Humanos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Glucagon/sangue , Glucagon/genética , Hipertensão Portal/sangue , Hipertensão Portal/etiologia , Hipertensão Portal/genética , Hipertensão Portal/cirurgia , Hipertrofia/genética , Cirrose Hepática , Doenças Genéticas Inatas/sangue , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/cirurgia , Pancreatopatias/genética , Pancreatopatias/patologia , Pancreatopatias/cirurgia , Células Secretoras de Glucagon/patologia
2.
BMC Genomics ; 25(1): 437, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698335

RESUMO

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.


Assuntos
Perfilação da Expressão Gênica , Transplante de Fígado , Fígado , Doadores de Tecidos , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Transcriptoma , Rejeição de Enxerto/genética , Adulto
3.
Am J Transplant ; 24(4): 619-630, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37940005

RESUMO

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.


Assuntos
Transplante de Fígado , Soluções para Preservação de Órgãos , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Doadores Vivos , Glucose , Manitol , Cloreto de Potássio , Procaína , Insulina , Glutationa , Alopurinol
4.
Liver Transpl ; 29(11): 1172-1180, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37379011

RESUMO

Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Adulto , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Doadores Vivos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doença Hepática Terminal/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Liver Transpl ; 29(11): 1151-1160, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37387680

RESUMO

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Fígado/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Doadores de Tecidos , Transplante Homólogo , Sobrevivência de Enxerto , Estudos Retrospectivos
6.
Neuromodulation ; 26(2): 320-332, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35219571

RESUMO

BACKGROUND: Deep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease. OBJECTIVE: In this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold). MATERIALS AND METHODS: STN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature. RESULTS: Both resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction. CONCLUSION: LFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Estimulação Encefálica Profunda/métodos , Movimento/fisiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/fisiologia , Resultado do Tratamento , Biomarcadores
7.
Liver Transpl ; 28(4): 623-635, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34564931

RESUMO

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%-29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score-matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long-term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high-risk macrosteatotic allografts to negatively affect outcomes.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Aloenxertos , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
8.
Transpl Int ; 35: 10175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865863

RESUMO

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC-1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years post-transplant was lower in NASH compared to non-NASH patients (5.80 vs. 9.41%, p = 0.01). Recurrence-free survival, however, was similar at 5 years between groups. Patients with NASH-related HCC were less likely to have post-transplant recurrence than their non-NASH counterparts, although recurrence-free survival was similar at 5 years.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
9.
Transpl Int ; 34(6): 1052-1064, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33884677

RESUMO

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.


Assuntos
Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Fígado , Políticas , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
10.
Int J Mol Sci ; 21(18)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32942580

RESUMO

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best. Chimeric antigen receptor (CAR) T cell therapy, effective in treating liquid tumors such as B-cell lymphoma, presents a potentially promising treatment option for advanced HCC. However, new challenges specific to solid tumors, such as tumor immunoanatomy or the immune cell presence and position anatomically and the tumor microenvironment, need to be defined and overcome. Immunotherapy currently in use must be re-engineered and re-envisioned to treat HCC with the hopes of ushering in an answer to advanced stage solid tumor disease processes. Future therapy options must address the uniqueness of the tumors under the umbrella of HCC. This review strives to summarize HCC, its staging system, current therapy and immunotherapy medications currently being utilized or studied in the treatment of HCC with the hopes of highlighting what is being done and suggesting what needs to be done in the future to champion this therapy as an effective option.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Linfócitos B/imunologia , Humanos , Imunoterapia/métodos , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
11.
Transpl Infect Dis ; 19(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28060446

RESUMO

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients.


Assuntos
Aloenxertos/virologia , Antivirais/uso terapêutico , Patógenos Transmitidos pelo Sangue/isolamento & purificação , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Acetaminofen/toxicidade , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Transmissão de Doença Infecciosa , Quimioterapia Combinada/efeitos adversos , Feminino , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Hepatite C/virologia , Humanos , Falência Renal Crônica/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico , Transplantados , Carga Viral
13.
Clin Transplant ; 30(1): 71-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26529289

RESUMO

Sensitization following renal allograft failure (AF) is highly variable. Some patients remain non-sensitized (NS), while others become highly sensitized (HS). We studied 66 NS patients who experienced AF after initial kidney transplantation. Post-failure, two main groups of NS panel reactive antibody (PRA) class I and II <10% and HS patients (PRA class I or II ≥80%) were identified. The impact of acute rejection (AR), immunosuppression withdrawal (ISW) at AF, allograft nephrectomy, graft intolerance syndrome (GIS), and both standard serologic and eplet-based mismatches (MM) in inducing HS status after failure was examined. Late PRA testing post-failure revealed 18 patients remained NS and 34 patients became HS. African American recipients, ISW at AF, DQB1 eplet MM, and presence of GIS were associated with becoming HS. Presence of total zero eplet MM, zero DQA1/B1 eplet MM, continuation of immunosuppression after failure, and a hyporesponsive immune status characterized by recurrent infections were features of NS patients. DQ eplet MM represents a significant risk for becoming HS after AF. Studies comparing ISW vs. continuation in re-transplant candidates with high baseline DQ eplet MM burden should be performed. This may provide insights if sensitization post-AF can be lessened.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA-DQ/imunologia , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim , Nefrectomia/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Teste de Histocompatibilidade , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/imunologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco
14.
Clin Nephrol ; 86(10): 175-82, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27616757

RESUMO

BACKGROUND: Efforts have been made to maximize the utility of each organ transplanted. Policy changes to capture unrealized graft years have been implemented utilizing the kidney donor profile index (KDPI). Understanding the impact of KDPI on long-term graft function is critical to an informed organ acceptance decision. METHODS: We reviewed the records of 309 consecutive deceased adult donor kidney recipients who underwent kidney transplantation at our center. We obtained KDPI of the allografts directly from United Network for Organ Sharing (UNOS) and patients were divided into four categories: KDPI ≤ 20, KDPI 21 - 35, KDPI 36 - 85, and KDPI > 85. RESULTS: Of the 309 recipients, 48 (15.5%) received kidneys from donors with KDPI ≤ 20, 57 (18.4%) from donors with KDPI 21 - 35, 161 (52.1%) from donors with KDPI 36 - 85, and 43 (13.9%) from donors with KDPI > 85. Older recipients were more likely to receive high KDPI kidneys (p = 0.025). Kaplan-Meier analysis demonstrated the KDPI > 35 group had worse survival than the KDPI ≤ 20 group, but KDPI 36 - 85 was not different from KDPI > 85. The rate of poor graft function differed at 1 year: 14.6% of KDPI ≤ 20 recipients, 14.3% of KDPI 21 - 35 recipients, 30.6% of KDPI 35 - 85 recipients, and 40.5% of KDPI > 85 recipients had serum creatinine greater than 2.0 mg/dL at 1 year. KDPI > 35 had statistically significantly greater incidence of poor graft function than KDPI ≤ 35 (p < 0.05). CONCLUSIONS: Our study demonstrates that high KDPI grafts behave more like moderate KDPI grafts (KDPI 35 - 85). Creatinine (Cr) greater than 2.0 mg/dL portends poorer long-term graft survival, and this outcome is similar amongst all recipients of KDPI > 35 allografts.
.


Assuntos
Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Rim/fisiologia , Doadores de Tecidos/estatística & dados numéricos , Adulto , Idoso , Creatinina/sangue , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Estudos Retrospectivos , Transplante Homólogo
15.
Clin Transplant ; 29(12): 1221-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26458498

RESUMO

Cytomegalovirus (CMV) is a common opportunistic infection encountered after pancreas transplantation. The records of 407 pancreas transplant recipients (226 simultaneous pancreas and kidney transplant (SPK), 101 pancreas transplant after kidney (PAK), and 97 pancreas transplants alone [PTA]) performed at a single center with at least 1-yr follow-up were reviewed. Immunosuppression included rabbit antithymocyte globulin induction, steroid withdrawal, and maintenance therapy of tacrolimus and sirolimus (± mycophenolate). In addition, PTA recipients received a single dose of rituximab. All recipients received valganciclovir prophylaxis. Donor (D)+/recipient (R)- recipients received 6 months of prophylaxis; all others received 3 months. The overall CMV infection rate was 12%. The cumulative incidences of CMV infection at 3, 6, 9, and 12 months after transplant were 0.25%, 3%, 7%, and 8%, respectively. CMV infection rates were 20.2% in the D+/R- group, 16.5% in the D+/R+ group, 5.0% in the D-/R+ group, and 2.8% in the D-/R- group. Infections were less common in SPK recipients. Most infections developed at least 3 months post-transplant, and 24% demonstrated tissue-invasive disease. Immunosuppression was NOT reduced in 72% of patients with infections. Ganciclovir-resistant CMV occurred in four patients. No patients died or lost their allografts due to CMV-related infection; one graft was lost due to chronic rejection associated with a reduction in immunosuppression. In many cases, CMV infections may be treated in pancreas transplant recipients without necessarily reducing immunosuppression.


Assuntos
Antibioticoprofilaxia , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/patogenicidade , Terapia de Imunossupressão/métodos , Transplante de Pâncreas/efeitos adversos , Adulto , Animais , Infecções por Citomegalovirus/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Coelhos , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
16.
World J Oncol ; 15(3): 511-520, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751709

RESUMO

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.

17.
Transplant Direct ; 10(7): e1663, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953038

RESUMO

Background: Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function. Methods: In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay. Results: There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ±â€…20.2 versus 71 ±â€…39.5 mg, P < 0.01). Postoperative pain scores were significantly lower (P < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter (P = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ±â€…907 versus 2168 ±â€…1347 mL, P = 0.049). Time to tolerating regular diet was shorter by 2 h (P < 0.008), and length of hospital stay was decreased by 10.1 h. Conclusions: The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.

19.
Clin Transplant ; 27(1): E49-55, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23228216

RESUMO

AIM: The goal of this study was to assess the impact of recipient age on post-transplant outcome. METHODS: All pancreas transplants performed at Indiana University between 2003 and 2011 were reviewed. Demographic data were compared using standard chi-square and ANOVA testing. Standard Cox regression survival analysis was performed using a direct entry method for covariates. RESULTS: Patients (n = 405) were divided by decade: <30 yr (n = 37), 30-39 (n = 109), 40-49 (n = 156), 50-59 (n = 85), and ≥ 60 yr of age (n = 18). Group demographics did not differ except for median ischemia time, which was between 7.0 and 8.5 h (p = 0.02). Early graft loss and one yr graft and patient survival were similar between the groups. Long-term patient survival demonstrated a trend toward decreased five-yr survival with increasing recipient age (p = NS). Graft survival at five yr by Cox regression was the lowest for the <30 yr group (74%), while all other groups were similar around 80% (p = NS). CONCLUSION: No statistically significant differences in pancreas transplant outcomes were demonstrated when recipients were stratified by recipient age. These results suggest that older recipients can successfully undergo pancreas transplantation and expect five-yr outcomes similar to those seen in younger recipients.


Assuntos
Sobrevivência de Enxerto , Transplante de Pâncreas/mortalidade , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Transplant Direct ; 9(11): e1521, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37829245

RESUMO

Background: Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods: Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results: Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%-100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%-100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios-VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions: Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.

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