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Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ11. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody that specifically targets mouse NINJ1 and blocks oligomerization of NINJ1, preventing PMR. Electron microscopy studies showed that this antibody prevents NINJ1 from forming oligomeric filaments. In mice, inhibition of NINJ1 or Ninj1 deficiency ameliorated hepatocellular PMR induced with TNF plus D-galactosamine, concanavalin A, Jo2 anti-Fas agonist antibody or ischaemia-reperfusion injury. Accordingly, serum levels of lactate dehydrogenase, the liver enzymes alanine aminotransaminase and aspartate aminotransferase, and the DAMPs interleukin 18 and HMGB1 were reduced. Moreover, in the liver ischaemia-reperfusion injury model, there was an attendant reduction in neutrophil infiltration. These data indicate that NINJ1 mediates PMR and inflammation in diseases driven by aberrant hepatocellular death.
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Anticorpos Monoclonais , Membrana Celular , Inflamação , Fígado , Fatores de Crescimento Neural , Traumatismo por Reperfusão , Animais , Camundongos , Alanina Transaminase , Alarminas , Anticorpos Monoclonais/imunologia , Aspartato Aminotransferases , Moléculas de Adesão Celular Neuronais/antagonistas & inibidores , Moléculas de Adesão Celular Neuronais/deficiência , Moléculas de Adesão Celular Neuronais/imunologia , Moléculas de Adesão Celular Neuronais/ultraestrutura , Morte Celular , Membrana Celular/patologia , Membrana Celular/ultraestrutura , Concanavalina A , Galactosamina , Hepatócitos/patologia , Hepatócitos/ultraestrutura , Inflamação/patologia , Lactato Desidrogenases , Fígado/patologia , Microscopia Eletrônica , Fatores de Crescimento Neural/antagonistas & inibidores , Fatores de Crescimento Neural/deficiência , Fatores de Crescimento Neural/imunologia , Fatores de Crescimento Neural/ultraestrutura , Infiltração de Neutrófilos , Traumatismo por Reperfusão/patologiaRESUMO
Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. 7,257 LDLT recipients with a median age of 54years (IQR:45,61), 54% male, 80% non-Hispanic White, BMI 26.3kg/m2 (IQR:23.2,30.0), and MELD 15 (IQR:11,19) were included. The median cold ischemic time was 1.6hours (IQR:1.0,2.3) with 88% right-lobe-grafts. The follow-up was 4.0years (IQR:1.0,9.2). The contemporary reached median overall survival was 17.0years (95%CI:16.1,18.1) with OS estimates: 1-year 95%, 3-years 89%, 5-years OS 84%, 10-years 72%, 15-years 56% and 20-years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (aHR 0.53; 95%CI:0.39,0.71). The median center-caseload per year was 5 (IQR:2,10) with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.
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OBJECTIVE: Assess the impact of having a living donor on waitlist outcomes and overall survival through an intention-to-treat analysis. BACKGROUND: Living-donor liver transplantation (LDLT) offers an alternative to deceased donation in the face of organ shortage. An as-treated analysis revealed that undergoing LDLT, compared to staying on the waiting list, is associated with improved survival, even at Model for End-stage Liver Disease-sodium (MELD-Na) score of 11. METHODS: Liver transplant candidates listed at the Ajmera Transplant Centre (2000-2021) were categorized as pLDLT (having a potential living donor) or pDDLT (without a living donor). Employing Cox proportional-hazard regression with time-dependent covariates, we evaluated pLDLT's impact on waitlist dropout and overall survival through a risk-adjusted analysis. RESULTS: Of 4,124 candidates, 984 (24%) had potential living donors. The pLDLT group experienced significantly lower overall waitlist dropouts (5.2%vs. 34.4%, P<0.001) and mortality (3.8%vs. 24.4%, P<0.001) compared to the pDDLT group. Possessing a living donor correlated with a 26% decline in the risk of waitlist dropout (adjusted hazard ratio 0.74, 95%CI 0.55-0.99, P=0.042). The pLDLT group also demonstrated superior survival outcomes at 1- (84.9%vs. 80.1%), 5- (77.6%vs. 61.7%), and 10-year (65.6%vs.52.9%) from listing (log-rank P<0.001) with a 35% reduced risk of death (adjusted hazard ratio 0.65, 95%CI 0.56-0.76, P<0.001). Moreover, the predicted hazard ratios consistently remained below 1 across the MELD-Na range 11-26. CONCLUSIONS: Having a potential living donor significantly improves survival in end-stage liver disease patients, even with MELD-Na scores as low as 11. This emphasizes the need to promote awareness and adoption of LDLT in liver transplant programs worldwide.
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BACKGROUND: Biliary complications are common in pediatric liver transplant. Strictures resistant to interventional radiology procedures can be extremely challenging to manage and may result in the need of surgery or retransplantation. METHODS: This case report illustrates the use of biodegradable stents post left lateral segment live donor liver transplant in a pediatric patient with a recalcitrant chronic stricture of the biliary-enteric anastomosis. The patient developed a high stricture requiring multiple interventions and eventual access of both the segment II and segment III ducts of the graft. RESULTS: To ensure adequate biliary drainage, two biodegradable stents were deployed using a "kissing-stent" technique. The stents were successfully deployed and allowed the patient to remain free from an internal-external biliary drain for 11 months, with eventual redeployment of an additional biodegradable stent. CONCLUSION: In patients with recalcitrant stenosis of the biliary anastomosis, biodegradable stents may provide durable drainage, optimizing graft function and delaying retransplantation in addition to keeping patients without external devices, thus improving quality of life.
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Transplante de Fígado , Humanos , Criança , Constrição Patológica/cirurgia , Doadores Vivos , Qualidade de Vida , StentsRESUMO
PURPOSE: The benefits of intraoperative dialysis during orthotopic liver transplantation remain controversial. In patients with anuric renal failure and portopulmonary hypertension, maintaining venous return during caval clamping and unclamping along with minimizing fluid overload is critical to avoiding right ventricular strain and failure. CLINICAL FEATURES: We present the case of a 54-yr-old female who underwent orthotopic liver transplantation for alcohol-related liver disease with acute decompensation including severe hepatorenal syndrome (anuric requiring dialysis), probable hepatopulmonary syndrome, moderate pulmonary hypertension (right ventricular systolic pressure, 44 mm Hg), hepatic encephalopathy (grade 2), and esophageal varices. Prior to incision, pulmonary arterial pressures were 48/28 (mean, 35) mm Hg with a central venous pressure of 30 mm Hg, cardiac output of 7.4 L·min-1, and pulmonary vascular resistance of 98 dynes·sec·cm-5. In the context of right ventricular strain and volume overload observed on transthoracic echocardiography, we inserted an additional dialysis catheter into the right femoral vein. We initiated dialysis using the two catheters as a circuit (femoral line to the dialysis machine; blood was reinjected via the subclavian line) acting as a limited venovenous bypass, allowing right ventricular offloading and hemodialysis throughout the case. We removed 4.5 L via hemodialysis during the surgery, while avoiding acidosis, hyperkalemia, and sodium shifts. The patient tolerated reperfusion adequately despite pre-existing right ventricular dilation and dysfunction. CONCLUSION: We report on the use two hemodialysis catheters in a patient undergoing orthotopic liver transplantation as a circuit for simultaneous anuric hepatorenal syndrome and moderate pulmonary hypertension with right ventricular dilation and dysfunction. We believe this technique was instrumental in the patient's successful transplant.
RéSUMé: OBJECTIF: Les avantages de la dialyse peropératoire pendant une transplantation hépatique orthotopique demeurent controversés. Chez la patientèle atteinte d'insuffisance rénale anurique et d'hypertension portopulmonaire, il est essentiel de maintenir le retour veineux pendant le clampage et le déclampage de la veine cave ainsi que de minimiser la surcharge hydrique, afin d'éviter la déformation et l'insuffisance ventriculaires droites. CARACTéRISTIQUES CLINIQUES : Nous présentons le cas d'une femme de 54 ans qui a bénéficié d'une transplantation hépatique orthotopique pour une maladie hépatique liée à l'alcool avec une décompensation aiguë comprenant un syndrome hépatorénal sévère (anurie nécessitant une dialyse), un syndrome hépatopulmonaire probable, une hypertension pulmonaire modérée (pression systolique ventriculaire droite, 44 mm Hg), une encéphalopathie hépatique (grade 2) et des varices Åsophagiennes. Avant l'incision, les pressions artérielles pulmonaires étaient de 48/28 (moyenne, 35) mm Hg avec une pression veineuse centrale de 30 mm Hg, un débit cardiaque de 7,4 L·min−1 et une résistance vasculaire pulmonaire de 98 dynes·sec·cm−5. Dans le contexte de la déformation ventriculaire et de la surcharge volémique droites observées à l'échocardiographie transthoracique, nous avons inséré un cathéter de dialyse supplémentaire dans la veine fémorale droite. Nous avons amorcé la dialyse en créant un circuit avec les deux cathéters (ligne fémorale en direction de l'appareil de dialyse; sang réinjecté via la ligne sous-clavière) agissant comme un pontage veino-veineux limité, permettant la décharge du ventricule droit et l'hémodialyse tout au long du cas. Nous avons retiré 4,5 L par hémodialyse pendant la chirurgie, tout en évitant l'acidose, l'hyperkaliémie et les changements en sodium plasmatique. La patiente a toléré la reperfusion de manière adéquate malgré la dilatation et le dysfonctionnement préexistants du ventricule droit. CONCLUSION: Nous rapportons l'utilisation de deux cathéters d'hémodialyse pour créer un circuit chez une patiente bénéficiant d'une transplantation hépatique orthotopique pour le traitement d'un syndrome hépatorénal anurique simultané à une hypertension pulmonaire modérée avec dilatation et dysfonctionnement du ventricule droit. Nous pensons que cette technique a joué un rôle déterminant dans la réussite de la greffe chez la patiente.
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Transplante de Fígado , Diálise Renal , Humanos , Pessoa de Meia-Idade , Feminino , Transplante de Fígado/métodos , Diálise Renal/métodos , Cuidados Intraoperatórios/métodos , Hipertensão Pulmonar/etiologia , Síndrome Hepatorrenal/etiologiaRESUMO
BACKGROUND AND AIMS: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. METHODS: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes. RESULTS: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001). CONCLUSIONS: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries.
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Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Doença Hepática Terminal/cirurgia , Índice de Gravidade de Doença , Doadores de Tecidos , Reino Unido/epidemiologia , Estudos Retrospectivos , Sobrevivência de Enxerto , Morte EncefálicaRESUMO
Differentiating hepatoblastomas from other congenital benign hepatic tumors is key to surgical management. We, herein, present an unusual case of an antenatally diagnosed liver lesion assessed in the neonatal period. Because of its predominantly cystic ultrasound/MRI appearance and borderline alpha-fetoprotein serum levels the diagnosis of mesenchymal hamartoma was favored and protocol-based tumor resection was performed. Due to the intraoperative diagnosis of a fetal subtype of hepatoblastoma with positive resection margins the child had to undergo a second laparotomy. This report raises awareness to an unusual appearance of hepatoblastoma and discusses noninvasive imaging clues to consider atypical appearances of hepatoblastoma preoperatively as they can have profound implications in patient management.
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Hamartoma , Hepatoblastoma , Neoplasias Hepáticas , Recém-Nascido , Criança , Humanos , Hepatoblastoma/diagnóstico , Hepatoblastoma/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Hamartoma/diagnóstico por imagem , Hamartoma/cirurgiaRESUMO
BACKGROUND: Liver transplantation is the life-saving treatment for many end-stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high-risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. AIMS: The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. METHODS: This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. RESULTS: Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20-13.51, p = .024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01-7.07, p = .049), 30-day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27-32.54, p = .002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12-9.81, p = .030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04-43.16, p = .004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00-343.90, p < .001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824-0.951). CONCLUSIONS: We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period.
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Transplante de Fígado , Humanos , Criança , Adolescente , Lactente , Estudos Retrospectivos , Tempo de Internação , Unidades de Terapia Intensiva , Fatores de RiscoRESUMO
Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.
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Carcinoma Hepatocelular , Hepatoblastoma , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/patologia , Criança , Hepatoblastoma/patologia , Hepatoblastoma/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
Paired organ exchange can be used to circumvent living donor-recipient ABO incompatibilities. Herein, we present the first case of successful liver paired exchange in North America. This 2-way swap required 4 simultaneous operations: 2 living donor hepatectomies and 2 living donor liver transplants. A nondirected anonymous living donor gift initiated this domino exchange, alleviating an ABO incompatibility in the other donor-recipient pair. With careful attention to ethical and logistical issues, paired liver exchange is a feasible option to expand the donor pool for incompatible living liver donor-recipient pairs.
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Transplante de Rim , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Humanos , Fígado , Doadores Vivos , América do Norte , Estados UnidosRESUMO
BACKGROUND: EPP is characterized by photosensitivity and by liver disease. When LT is performed in EPP, recurrence often occurs in the allograft due to ongoing protoporphyrin production in bone marrow. Therefore, curative treatment requires allogeneic HSCT after LT. Long-term immunosuppression could be spared by using the same donor for both transplants. METHODS: A 2-year-old girl with EPP in liver failure underwent liver transplant from her father. Transfusion and apheresis therapy were used to lower protoporphyrin levels before and after liver transplant. Ten weeks after liver transplant, she underwent HSCT, using the same donor. Conditioning was with treosulfan, fludarabine, cyclophosphamide, and ATG. GVHD prophylaxis was with abatacept, methotrexate, MMF, and tacrolimus. We followed the patient's erythrocyte protoporphyrin and liver and skin health for 2 years after transplant. RESULTS: After hematopoietic stem cell engraftment, a decline in protoporphyrin levels was observed, with clinical resolution of photosensitivity. Liver biopsies showed no evidence of EPP. Mild ACR occurred and responded to steroid pulse. Two years post-HSCT, the patient has been weaned off all immunosuppression and remains GVHD and liver rejection free. CONCLUSIONS: Sequential liver and HSCT from the same haploidentical donor are feasible in EPP. This strategy can allow for discontinuation of immune suppression.
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Transplante de Células-Tronco Hematopoéticas , Transplante de Fígado , Porfiria Eritropoética/cirurgia , Transplante Haploidêntico , Biópsia , Feminino , Humanos , Lactente , Doadores Vivos , Masculino , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is rare in children and there is limited data on its imaging features. OBJECTIVE: To describe imaging features of pediatric HCC and correlate them with clinical and laboratory findings. MATERIALS AND METHODS: We retrospectively reviewed imaging in all pediatric HCC cases seen between January 2000 and January 2019. Imaging features defined in LI-RADS (Liver Imaging Reporting and Data System) and tumor extent by PRETEXT (pretreatment extent of disease) criteria were noted by two radiologists. Patient charts were reviewed to collect clinical features, alpha-fetoprotein (AFP) level and pathology findings. RESULTS: Of the 15 children (7 boys, 8 girls; mean age: 11.8 years, age range: 6-17 years) included in the study, 12/15 had computed tomography, 9/15 had magnetic resonance imaging and 9/15 had ultrasound exams available for review. Pathological types of HCC included classic (11/15, 73%), fibrolamellar (3/15, 20%) and mixed cholangiocarcinoma-HCC (1/15, 7%). Eighty percent occurred de novo in normal liver and 67% showed elevated AFP levels. Arterial phase hyperenhancement was seen in 83% of cases, washout in 86%, capsule in 50% and tumor-in-vein in 33%. The mean tumor size was 9.8 cm and 40% were multifocal on imaging. Staging revealed PRETEXT II tumors in 47%, III in 20% and IV in 33%. There were no PRETEXT I tumors. The two most common PRETEXT annotation factors were portal vein and caudate lobe involvement in 71% and 43% of cases, respectively. Fibrolamellar HCC demonstrated central scar, normal AFP levels and normal background liver. CONCLUSION: Pediatric HCC are large heterogeneous tumors, as reflected by high PRETEXT staging, and commonly include portal vein and caudate involvement. This affects resectability of these tumors at presentation. Central scar, normal AFP level and normal liver background may help differentiate fibrolamellar HCC from other types of HCC.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adolescente , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Criança , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
Screening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)-based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55-69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.
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Detecção Precoce de Câncer , Transplante de Rim , Complicações Pós-Operatórias/diagnóstico , Neoplasias da Próstata/diagnóstico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos RetrospectivosRESUMO
Kidney transplantation is the preferred treatment for pediatric end-stage renal disease (ESRD). Preemptive transplantation avoids the increased morbidity and mortality of dialysis. Yet, previous studies have not demonstrated significant graft or patient survival benefits for children undergoing transplantation preemptively versus nonpreemptively. These previous studies were limited by small samples sizes and low rates of adverse events. Here we compared graft failure and mortality rates using Kaplan-Meier methods and Cox regression among a large national cohort of children with ESRD undergoing preemptive versus nonpreemptive kidney transplantation between 2000 and 2012. Among 7527 pediatric kidney transplant recipients in the United States Renal Data System, 1668 underwent preemptive transplantation. Over a median 4.8 years follow-up, 1314 experienced graft failure, and over a median 5.2 years of follow-up, 334 died. Dialysis exposure versus preemptive transplantation conferred a higher risk of graft failure (hazard ratio 1.32; 95% confidence interval: 1.10-1.56) and a higher risk of death (hazard ratio 1.69; 95% confidence interval: 1.22-2.33) in multivariable analysis. Compared with children undergoing preemptive transplantation, children on dialysis for >1 year had a 52% higher risk of graft failure and those on dialysis >18 months had an 89% higher risk of death, regardless of donor source. Thus, preemptive transplantation is associated with substantial benefits in allograft and patient survival among children with ESRD, particularly when compared with children who receive dialysis for >1 year. These findings support policies to promote early access to transplantation and avoidance of dialysis for children with ESRD whenever feasible.
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Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/mortalidade , Masculino , Falha de Tratamento , Estados Unidos/epidemiologiaRESUMO
PURPOSE OF REVIEW: Advances in surgical technique and immunosuppression have significantly improved outcomes after pancreas transplantation, and as a result pancreas transplants increasingly are being performed for indications other than type 1 diabetes mellitus. This review summarizes the current literature on pancreas transplantation in unconventional recipient populations. RECENT FINDINGS: An increasing body of work suggests that pancreas transplantation can be performed with good outcomes in patients with type 2 diabetes mellitus and those 50 years of age and older. Obesity appears detrimental to patient and pancreas graft survival, and bariatric surgery prior to transplantation may be of increasing interest and relevance. There are limited data yielding mixed outcomes on pancreas transplantation in patients with HIV or hepatitis C virus. However, rapidly improving antiviral therapies are prolonging survival in patients with HIV and chronic hepatitis C virus infections and may increase the number of candidates available for pancreas transplantation in these populations in the future. SUMMARY: Despite limited literature in these patient populations, pancreas transplantation may be a viable treatment option for endocrine pancreas failure in appropriately selected patients regardless of disease cause or age.
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Diabetes Mellitus Tipo 2/terapia , Transplante de Pâncreas , Humanos , Seleção de PacientesAssuntos
Veia Ilíaca/transplante , Transplante de Fígado/métodos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Enxerto Vascular/métodos , Veia Cava Inferior/transplante , Aloenxertos/anatomia & histologia , Aloenxertos/irrigação sanguínea , Humanos , Lactente , Fígado/anatomia & histologia , Fígado/irrigação sanguínea , Masculino , Tamanho do Órgão , Resultado do TratamentoRESUMO
Polymers are endocytosed and hydrolysed by lysosomal enzymes to generate transportable solutes. While the transport of diverse organic solutes across the plasma membrane is well studied, their necessary ongoing efflux from the endocytic fluid into the cytosol is poorly appreciated by comparison. Myeloid cells that employ specialized types of endocytosis, that is, phagocytosis and macropinocytosis, are highly dependent on such transport pathways to prevent the build-up of hydrostatic pressure that otherwise offsets lysosomal dynamics including vesiculation, tubulation and fission. Without undergoing rupture, we found that lysosomes incurring this pressure owing to defects in solute efflux, are unable to retain luminal Na+, which collapses its gradient with the cytosol. This cation 'leak' is mediated by pressure-sensitive channels resident to lysosomes and leads to the inhibition of mTORC1, which is normally activated by Na+-coupled amino acid transporters driven by the Na+ gradient. As a consequence, the transcription factors TFEB/TFE3 are made active in macrophages with distended lysosomes. In addition to their role in lysosomal biogenesis, TFEB/TFE3 activation causes the release of MCP-1/CCL2. In catabolically stressed tissues, defects in efflux of solutes from the endocytic pathway leads to increased monocyte recruitment. Here we propose that macrophages respond to a pressure-sensing pathway on lysosomes to orchestrate lysosomal biogenesis as well as myeloid cell recruitment.