RESUMO
Chronic kidney disease affects an estimated 37 million people in the United States; of these,>800,000 have end-stage renal disease requiring chronic dialysis or a kidney transplant to survive. Despite efforts to increase the donor kidney supply, approximately 100,000 people are registered on the kidney transplant wait-list with no measurable decrease over the past 2 decades. The outcomes of kidney transplantation are significantly better than for chronic dialysis: kidney transplant recipients have lower rates of mortality and cardiovascular events and better quality of life, but wait-list time matters. Time on dialysis waiting for a deceased-donor kidney is a strong independent risk factor for outcomes after a kidney transplant. Deceased-donor recipients with wait-list times on dialysis of<6 months have graft survival rates equivalent to living-donor recipients with waitlist times on dialysis of>2 years. In 2021,>12,000 people had been on the kidney transplant waitlist for ≥5 years. As the gap between the demand for and availability of donor kidneys for allotransplantation continues to widen, alternative strategies are needed to provide a stable, sufficient, and timely supply. A strategy that is gaining momentum toward clinical application is pig-to-human kidney xenotransplantation. This report summarizes the proceedings of a meeting convened on April 11-12, 2022, by the National Kidney Foundation to review and assess the state of pig-to-human kidney xenotransplantation as a potential cure for end-stage renal disease.
Assuntos
Falência Renal Crônica , Transplante de Rim , Humanos , Falência Renal Crônica/cirurgia , Animais , Listas de Espera , Xenoenxertos , Estados Unidos/epidemiologia , Fundações , Transplante Heterólogo , Sobrevivência de EnxertoRESUMO
Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs. While therapeutics exist that can help mitigate the detrimental effects of antibodies, they act broadly potentially dampening beneficial immunity. Identifying additional xenoantigens may enable more targeted approaches, such as gene editing, to overcome these challenges by further eliminating antibody targets on donor tissue. Because we have found that classical class I swine leukocyte antigens are targets of human antibodies, we now examine whether related pig proteins may also be targeted by human antibodies. We show here that non-classical class I swine leukocyte proteins (SLA-6, -7, -8) can be expressed at the surface of mammalian cells and act as antibody targets.
Assuntos
Antígenos Heterófilos , Antígenos de Histocompatibilidade Classe I , Transplante Heterólogo , Animais , Suínos , Transplante Heterólogo/métodos , Antígenos Heterófilos/imunologia , Humanos , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Rejeição de Enxerto/imunologia , Animais Geneticamente ModificadosRESUMO
Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α-granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.
Assuntos
Células Endoteliais , Trombocitopenia , Suínos , Animais , Humanos , Transplante Heterólogo/métodos , Fígado , Plaquetas , Trombocitopenia/etiologia , Antígenos Heterófilos , Imunoglobulina G , Imunoglobulina MRESUMO
OBJECTIVE: Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression. METHODS: Double (Gal and Sda) and triple xenoantigen (Gal, Sda, and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70âdays, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n = 7). Control recipients did not receive anti-C5 therapy (n = 10). RESULTS: Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival (P < 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62âdays. CONCLUSION: Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Transplante de Rim , Transplante Heterólogo , Animais , Animais Geneticamente Modificados , Antibioticoprofilaxia , Tolerância Imunológica , Macaca mulatta , Modelos Animais , Rituximab/farmacologia , Suínos , Tacrolimo/farmacologiaRESUMO
The shortage of available organs remains the greatest barrier to expanding access to transplant. Despite advances in genetic editing and immunosuppression, survival in experimental models of kidney xenotransplant has generally been limited to <100 days. We found that pretransplant selection of recipients with low titers of anti-pig antibodies significantly improved survival in a pig-to-rhesus macaque kidney transplant model (6 days vs median survival time 235 days). Immunosuppression included transient pan-T cell depletion and an anti-CD154-based maintenance regimen. Selective depletion of CD4+ T cells but not CD8+ T cells resulted in long-term survival (median survival time >400 days vs 6 days). These studies suggested that CD4+ T cells may have a more prominent role in xenograft rejection compared with CD8+ T cells. Although animals that received selective depletion of CD8+ T cells showed signs of early cellular rejection (marked CD4+ infiltrates), animals receiving selective CD4+ depletion exhibited normal biopsy results until late, when signs of chronic antibody rejection were present. In vitro study results suggested that rhesus CD4+ T cells required the presence of SLA class II to mount an effective proliferative response. The combination of low pretransplant anti-pig antibody and CD4 depletion resulted in consistent, long-term xenograft survival.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Tolerância Imunológica/imunologia , Transplante de Rim/efeitos adversos , Depleção Linfocítica/efeitos adversos , Animais , Rejeição de Enxerto/patologia , Xenoenxertos , Macaca mulatta , SuínosRESUMO
OBJECTIVE: Xenotransplantation using pig organs could end the donor organ shortage for transplantation, but humans have xenoreactive antibodies that cause early graft rejection. Genome editing can eliminate xenoantigens in donor pigs to minimize the impact of these xenoantibodies. Here we determine whether an improved cross-match and chemical immunosuppression could result in prolonged kidney xenograft survival in a pig-to-rhesus preclinical model. METHODS: Double xenoantigen (Gal and Sda) knockout (DKO) pigs were created using CRISPR/Cas. Serum from rhesus monkeys (n = 43) was cross-matched with cells from the DKO pigs. Kidneys from the DKO pigs were transplanted into rhesus monkeys (n = 6) that had the least reactive cross-matches. The rhesus recipients were immunosuppressed with anti-CD4 and anti-CD8 T-cell depletion, anti-CD154, mycophenolic acid, and steroids. RESULTS: Rhesus antibody binding to DKO cells is reduced, but all still have positive CDC and flow cross-match. Three grafts were rejected early at 5, 6, and 6 days. Longer survival was achieved in recipients with survival to 35, 100, and 435 days. Each of the 3 early graft losses was secondary to IgM antibody-mediated rejection. The 435-day graft loss occurred secondary to IgG antibody-mediated rejection. CONCLUSIONS: Reducing xenoantigens in donor pigs and chemical immunosuppression can be used to achieve prolonged renal xenograft survival in a preclinical model, suggesting that if a negative cross-match can be obtained for humans then prolonged survival could be achieved.
Assuntos
Antígenos Heterófilos/imunologia , Sobrevivência de Enxerto/imunologia , Terapia de Imunossupressão/métodos , Imunossupressores/farmacologia , Transplante de Rim , Animais , Animais Geneticamente Modificados , Antígenos Heterófilos/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Sobrevivência de Enxerto/efeitos dos fármacos , Imunoglobulina M/imunologia , Macaca mulatta , Suínos , Transplante HeterólogoRESUMO
INTRODUCTION: Aggressive recurrence of hepatitis C remains problematic post-orthotopic liver transplant (OLT). There are limited data on treatment of HCV infection with telaprevir/boceprevir therapy with peginterferon/ribavirin (PR) post-OLT. AIM: To review our experience with telaprevir addition to peginterferon/ribavirin in treatment of aggressive hepatitis C in null responders to PR post-OLT. METHODS: Adult patients with recurrent HCV infection post-OLT with null response to peginterferon/ribavirin for 12 wk (<2 log reduction) received four-wk lead-in PEG-IFN alfa-2b (1.0 µg/kg/wk) plus RBV (600-1000 mg/d) followed by addition of telaprevir 750 q8. All patients were converted to cyclosporine from tacrolimus (TAC). RESULTS: Seven patients (3 M, 4 F), mean age 56 yr, were treated. Three were <1 yr post-OLT, six had cirrhosis and one bridging fibrosis. Three of seven achieved sustained virologic response. All patients required RBV dose reduction, 6/7 required erythropoietin, 5/7 required filgrastim, and 2/7 required eltrombopag for platelets <20 000 µL. There were no supratherapeutic/subtherapeutic CYA levels encountered, no episodes of renal insufficiency. CONCLUSIONS: Conversion to CYA followed by four-wk peginterferon/ribavirin lead-in with addition of telaprevir can lead to significant clearance rates at week 24 in null responders with advanced fibrosis although high rates of anemia/RBV dose reduction, growth factor, and transfusion requirements were noted.
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/etiologia , Hepatite C/cirurgia , Humanos , Interferon alfa-2 , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Proteínas Recombinantes/uso terapêutico , Recidiva , Retratamento , Fatores de Risco , Carga ViralRESUMO
BACKGROUND: The U.S. incidence of hepatocellular carcinoma (HCC) is increasing and is linked to hepatitis C (HepC) infection, alcohol toxicity, and obesity. This manuscript examines lysophosphatidic acid (LPA) variant biosynthesis as a biomarker and potential therapeutic target for HCC. METHODS: Serum LPA variant levels were determined in patients with HepC ± HCC, alcoholic cirrhosis ± HCC, or nonalcoholic steatohepatitis ± HCC by mass spectroscopy. To clarify the relationship between cancer and LPA variant profiles, LPA variants were evaluated in HepC + HCC patients before and after liver transplantation. Moreover, LPA variant modification of gene expression was also determined in vitro by real-time polymerase chain reaction. RESULTS: In patients diagnosed with HCC, 18:2 LPA biosynthesis was decreased, whereas 20:4 LPA biosynthesis and 20:4 LPA:18:2 LPA ratio were increased. Three days after liver transplantation, serum LPA levels and 18:2 LPA:20:4 LPA ratio were significantly reduced in patients with cancer. The 20:4 LPA selectively stimulated LPA receptor and tumor necrosis factor α expression in Hep3B cells, whereas 18:2 LPA did not. CONCLUSIONS: Serum LPA variant profiles are unique in patients with HCC allowing for the stratification of patients. Moreover, LPA variants impart individual mitogenic properties associated with tumorigenesis that may provide a potential therapeutic target. We envision that LPA profiling may accelerate diagnosis, help stratify patients at high risk of developing cancer, and provide potential targets for chemoprevention.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Lisofosfolipídeos/sangue , Fígado Gorduroso/metabolismo , Hepatite C/metabolismo , Humanos , Transplante de Fígado , Lisofosfolipídeos/biossíntese , Espectrometria de Massas , Hepatopatia Gordurosa não Alcoólica , RNA Mensageiro/análise , Receptores de Ácidos Lisofosfatídicos/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Little is known about the clonality of Staphylococcus epidermidis in the United States, although it is the predominant pathogen in infections involving prosthetic materials, including ventricular assist devices (VADs). METHODS: Seventy-five VAD recipients at 4 geographically diverse US cardiac centers were prospectively followed up to 1 year of VAD support. The anterior nares, sternum, and (future) driveline exit site were cultured for S. epidermidis before VAD insertion and at 7 times after surgery. Infection isolates were also collected. Isolates were typed by pulsed-field gel electrophoresis. A subset underwent susceptibility testing and staphylococcal chromosomal cassette mec and multilocus sequence typing. RESULTS: A total of 1559 cultures yielded 565 S. epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal types as defined by pulsed-field gel electrophoresis. These clones were identified in up to 27 people distributed across all 4 cardiac centers. They caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic resistant than were less prevalent isolates (eg, 79% vs 54% methicillin resistant; P = .0021). CONCLUSIONS: This study revealed that healthcare-associated S. epidermidis infection is remarkably clonal. We describe S. epidermidis clones that are highly resistant to antibiotics distributed across US cardiac centers. These clones may have determinants that enhance transmissibility, persistence, or invasiveness. Clinical Trials Registration. NCT01471795.
Assuntos
Coração Auxiliar/microbiologia , Resistência a Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus/métodos , Estudos Prospectivos , Manejo de Espécimes , Infecções Estafilocócicas/epidemiologia , Staphylococcus epidermidis/efeitos dos fármacos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Renal transplantation is the preferred treatment of ESKD, but the shortage of suitable donor kidneys from the cadaver pool means that many patients with ESKD will not receive a kidney transplant. Xenotransplantation has long represented a solution to the kidney shortage, but the occurrence of antibody-mediated rejection has precluded its clinical development. Developments in somatic cell nuclear transfer in pigs and gene editing tools have led to the creation of new donor pigs with greatly improved crossmatches to patients. In addition, improvements in preclinical kidney xenotransplant survival using new anti-CD40/CD154-based immunosuppression have pushed xenotransplantation to the point where it is reasonable to consider initiating a clinical trial to evaluate this potential therapy in patients.
Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Animais , Animais Geneticamente Modificados , Sobrevivência de Enxerto/genética , Rim , Suínos , Transplante Heterólogo , HumanosRESUMO
Seventy to ninety percentage of preformed xenoreactive antibodies in human serum bind to the galactose-α(1,3)-galactose Gal epitope, and the creation of Gal knockout (KO) pigs has eliminated hyperacute rejection as a barrier to xenotransplantation. Now other glycan antigens are barriers to move ahead with xenotransplantation, and the N-glycolyl neuraminic acid, Neu5Gc (or Hanganutziu-Deicher antigen), is also a major pig xenoantigen. Humans have anti-Neu5Gc antibodies. Several data indicate a strong immunogenicity of Neu5Gc in humans that may contribute to an important part in antibody-dependent injury to pig xenografts. Pig islets express Neu5Gc, which reacted with diet-derived human antibodies and mice deleted for Neu5Gc reject pancreatic islets from wild-type counterpart. However, Neu5Gc positive heart were not rejected in Neu5Gc KO mice indicating that the role of Neu5Gc-specific antibodies has to be nuanced and depend of the graft situation parameters (organ/tissue, recipient, implication of other glycan antigens). Recently generated Gal/Neu5Gc KO pigs eliminate the expression of Gal and Neu5Gc, and improve the crossmatch of humans with the pig. This review summarizes the current and recent experimental and (pre)clinical data on the Neu5Gc immunogenicity and emphasize of the potential impact of anti-Neu5Gc antibodies in limiting xenotransplantation in humans.
Assuntos
Anticorpos Heterófilos/metabolismo , Rejeição de Enxerto/imunologia , Xenoenxertos/imunologia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/imunologia , Ácidos Neuramínicos/imunologia , Transplante Heterólogo , Animais , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Humanos , SuínosRESUMO
Portal vein thrombosis is the most common cause of portal hypertension in noncirrhotic patients. Variceal bleeding is difficult to treat in these patients, especially those with prehepatic diffuse portal mesenteric thrombosis. In a patient with refractory esophagogastroduodenal variceal bleeding as a result of diffuse portomesenteric thrombosis and portal hypertension, life-threatening bleeding was unresponsive to endoscopic therapy and other surgical procedures. A multivisceral transplant was performed. It was curative and also lifesaving. There is only one report in the literature mentioning multivisceral transplantation for a patient with life-threatening esophagogastroduodenal bleeding; however that patient had protein C deficiency. Our patient had normal liver and intestinal function tests and no signs of hypercoagulable disease. We believe that multivisceral transplantation should be considered as a treatment option for patients with diffuse mesenteric thrombosis, even in the absence of liver and intestinal failure, when other treatment options for variceal bleeding have failed, particularly in a younger patient with a relatively good nutritional status before transplantation.
Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Transplante de Fígado , Veias Mesentéricas , Transplante de Pâncreas , Veia Porta , Trombose Venosa/complicações , Vísceras/transplante , Adulto , Angiografia , Endoscopia Gastrointestinal , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Hipertensão Portal/cirurgia , Intestino Delgado/transplante , Imageamento por Ressonância Magnética , Masculino , Estômago/transplante , Trombose Venosa/diagnósticoRESUMO
INTRODUCTION: CTLA-4 is a negative regulatory molecule upregulated on activated T cells; however, its role in induction and maintenance of transplant tolerance is not well understood. METHODS: The characteristics and effects of a novel mouse anti-rat CTLA-4 antibody (Ab) (242B58) were examined using fluorescence-activated cell sorter, mixed lymphocyte reaction, enzyme-linked immunospot, signaling studies, and a rat model of cardiac transplant tolerance induced by administration of anti-CD28 Ab and cyclosporine. RESULTS: The anti-CTLA4 Ab was shown to bind to CTLA-4 but not prevent subsequent binding of B7 to CTLA-4. Binding to CTLA-4 did not result in phosphorylation of early cytoplasmic tyrosine kinases, suggesting that this is not a signaling Ab. However, its in vitro function was compatible with antagonization of the effects of CTLA-4, thereby increasing T-cell proliferation and interferon-gamma production in mixed lymphocyte reaction and enzyme-linked immunospot assays, respectively. Administration of 242B58 to animals treated with anti-CD28 Ab and cyclosporine either at the time of transplantation or various time-points up to 33 days posttransplantation did not result in immediate rejection, but rather caused a delayed severe acute allograft rejection at approximately 45 days posttransplant. CONCLUSIONS: Our results seem to be a reflection of the unique properties of the 242B58 Ab, which does not antagonize B7 binding to CTLA-4 and affect its ability to out-compete CD28 for B7 binding. It does, however, seem to interfere with CTLA-4 signaling, suggesting that competition for B7 may be important in induction of tolerance, but signaling through CTLA-4 is more important in maintaining a tolerant phenotype.
Assuntos
Antígenos de Diferenciação/metabolismo , Sobrevivência de Enxerto/imunologia , Transplante de Coração/imunologia , Tolerância Imunológica/imunologia , Animais , Anticorpos/imunologia , Antígenos CD , Antígenos de Diferenciação/imunologia , Antígeno B7-1/metabolismo , Antígeno CTLA-4 , Rejeição de Enxerto/imunologia , Teste de Cultura Mista de Linfócitos , Camundongos , Fosfotirosina/metabolismo , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , Ratos , Fatores de TempoRESUMO
OBJECTIVE: The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? METHODS: We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. RESULTS: The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. CONCLUSION: The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.
Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Coração Auxiliar , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/terapia , Idoso , Intervalos de Confiança , Cuidados Críticos , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Modelos de Riscos Proporcionais , Qualidade de Vida , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Listas de EsperaRESUMO
OBJECTIVE: The Levitronix CentriMag (Levitronix LLC, Waltham, Mass) ventricular assist system is designed for temporary left, right, or biventricular support. Advantages include ease of use, excellent reliability, and low thrombosis risk,. which may allow wider application of short-term support and improved outcomes in patients with cardiogenic shock. This multi-institutional study evaluated safety, effectiveness, and outcomes of the CentriMag in patients with cardiogenic shock. METHODS: Thirty-eight patients were supported at 7 centers. Patients included 12 after cardiotomy, 14 after myocardial infarction, and 12 with right ventricular failure after implantable left ventricular assist device placement. Devices were implanted in left (n = 8), right (n = 12), or biventricular (n = 18) configuration. Support was continued until recovery, transplantation, or implantation of long-term ventricular assist device. RESULTS: Mean support duration for the entire cohort (n = 38) was 13 days (1-60 days), with 47% of patients (18/38) surviving 30 days after device removal. Mean CentriMag biventricular support (n = 18) duration was 15 days (1-60 days), with 44% (8/18) surviving at 30 days. Mean CentriMag right ventricular support with a commercially available left ventricular assist device (n = 12) duration was 14 days (1-29 days), with 58% (7/12) surviving at 30 days. Complications included bleeding (21%), infection (5%), respiratory failure (3%), hemolysis (5%), and neurologic dysfunction (11%). There were no CentriMag or pump failures. CONCLUSIONS: In this preliminary study, the CentriMag provided short-term support for patients with cardiogenic shock with a low incidence of device-related complications and no device failures.
Assuntos
Coração Auxiliar , Choque Cardiogênico/terapia , Adulto , Idoso , Feminino , Coração Auxiliar/efeitos adversos , Hemodinâmica , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Desenho de Prótese , Recuperação de Função Fisiológica , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Tromboembolia/etiologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Função Ventricular Esquerda , Função Ventricular DireitaRESUMO
BACKGROUND: Given the large number of patients undergoing cardiac operations annually, it is important to identify populations at high risk for adverse outcomes. This observational study was conducted to determine the incidence of preoperative heparin-platelet factor 4 (HPF4) antibodies and to assess the associated risk of postoperative adverse outcomes in a nonselected cardiac surgery patient population. METHODS: Between March 2002 and December 2004, 1114 (92%) of 1209 patients undergoing cardiac surgery with heparin were tested in an unselected manner for HPF4 antibodies. Main outcome measures were HPF4 antibody seropositivity and fatal and nonfatal adverse clinical outcomes after cardiac surgery. RESULTS: Of those screened, 60 (5.4%) of 1114 had positive HPF4 antibodies preoperatively. These patients had longer mean postoperative length of stay (14.0 days versus 9.8 days, p = 0.05), a higher incidence of prolonged (> or = 96 hours) mechanical ventilation (20.3% versus 9.2%, p = 0.02), acute limb ischemia (5.1% versus 0.9%, p = 0.03), renal complications including dialysis (20.3% versus 10.5%, p = 0.03), and gastrointestinal complications (15.3% versus 5.9%, p = 0.01). Stepwise logistic regression analysis showed positive HPF4 antibody status to be an independent predictor for adverse outcome and was associated with a higher risk for renal complications, including dialysis (adjusted odds ratio 2.2; 95% confidence interval, 1.1 to 4.3), than was diabetes. CONCLUSIONS: In this large patient series, the presence of HPF4 antibodies before surgical heparin administration was an independent and clinically significant risk factor for postoperative adverse events after cardiac surgery. An optimal preoperative cardiac surgery risk profile should include HPF4 antibody status.
Assuntos
Anticoagulantes/imunologia , Procedimentos Cirúrgicos Cardíacos , Heparina/imunologia , Fator Plaquetário 4/imunologia , Trombocitopenia/induzido quimicamente , Idoso , Anticorpos , Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombocitopenia/imunologia , Resultado do TratamentoRESUMO
OBJECTIVE: To present a case that demonstrates the evolution of a pheochromocytoma over a several-year period and to emphasize the importance of a thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1 (NF1) and hypertension. METHODS: We review the long-term clinical, biochemical, and imaging findings in a man with a complex medical history of hypertension, NF1, and cardiomyopathy. RESULTS: A 44-year-old man, with a well-documented history of headaches, hypertension, and NF1, was referred for evaluation of a right adrenal enlargement. He had developed cardiomyopathy and undergone an evaluation for cardiac transplantation. Initial computed tomography revealed subtle asymmetry in the upper right adrenal gland. Biochemical studies for pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the urinary norepinephrine and near-normal urinary metanephrine level. Because 131I-metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right adrenal gland, the patient was thought not to have a pheochromocytoma. The patient eventually underwent cardiac transplantation and did well. On reassessment 3 1/2 years later, he was found to have a larger right adrenal mass. The second endocrine evaluation demonstrated substantial elevation in the urinary metanephrine level, and the patient underwent laparoscopic right adrenalectomy to remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma. CONCLUSION: This case shows that a pheochromocytoma can be difficult to diagnose and can evolve to become a large, biochemically active tumor. It is imperative that patients with an adrenal tumor undergo periodic reevaluation to ensure that the tumor remains stable in size. If the tumor enlarges, further biochemical testing is warranted.
Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Progressão da Doença , Feocromocitoma/complicações , 3-Iodobenzilguanidina , Abdome/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Creatinina/urina , Dopamina/urina , Epinefrina/urina , Humanos , Hipertensão/complicações , Hipertensão/urina , Masculino , Metanefrina/urina , Neurofibromatose 1/complicações , Neurofibromatose 1/urina , Norepinefrina/urina , Normetanefrina/urina , Feocromocitoma/cirurgia , Feocromocitoma/urina , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
We compared the survival outcomes, left ventricular assist device (LVAD)-related hospitalization, stroke, infection, panel reactive antibody, and blood product use data among 13 Novacor and 51 HeartMate system recipients. Stroke was significantly higher in Novacor patients, as was blood product use at the time of heart transplantation, likely due to long-term anti-coagulation, while the LVAD-related hospitalization and infections did not differ between the 2 groups. A positive panel reactive antibody was seen more among the HeartMate patients, but did not have a significant clinical impact and may not represent a true allosensitization.