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1.
Gac Med Mex ; 159(4): 331-336, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37699225

RESUMEN

BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rate higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. OBJECTIVES: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. MATERIAL AND METHODS: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. RESULTS: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. CONCLUSION: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.


ANTECEDENTES: El tratamiento del virus de la hepatitis C (VHC) crónica con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). OBJETIVO: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). MATERIAL Y MÉTODOS: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. RESULTADOS: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. CONCLUSIÓN: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Hígado , Humanos , Sofosbuvir/uso terapéutico , Terapia Recuperativa , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Estudios Retrospectivos
2.
Surg Endosc ; 34(3): 1324-1329, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31190224

RESUMEN

BACKGROUND: An international group proposed a standardized terminology to report outcomes after bile duct repair. Data on this surgical complication vary depending on the center and country where patients are treated. The aim of this work is to show disparities in the care process of bile duct injury between patients from two different income-level countries, using a standard terminology of outcomes and clinical reporting. METHODS: A retrospective review comparing primary repair and re-repaired cases performed in an upper middle-income country (UMIC) versus primary repair cases treated in a high-income country (HIC) was performed. All pertinent data included in the tabular reporting system and outcomes classification were collected. Patients' characteristics were reported by calculating descriptive statistics. RESULTS: A total of 261 patients from UMIC (148 (56%) primary repair and 113 (44%) re-repair) were compared with 122 primary repair from HIC. Open cholecystectomy (55.4% vs 3.3%) and more E4 injuries (37.8% vs 19.7%) were found in the UMIC group. More Accordion 3 and higher complications were present in the UMIC primary and repair groups, as well as more episodes of postoperative acute cholangitis. Eleven patients were listed for liver transplant in the UMIC re-repair group. Primary patency by the end of the index treatment period was present in 217 (83%) of the full UMIC cohort. Median time to loss of primary patency was not reached in the primary repair, and was 3.8 years in the re-repair group. Patency was below HIC primary repaired cases. CONCLUSIONS: Standardized reporting outcomes after primary repair are applicable to re-repaired patients and are helpful to compare different populations, showing better outcomes in HIC. Measures of surgical access disparities exist among the process of bile duct injury care.


Asunto(s)
Conductos Biliares , Colecistectomía , Disparidades en Atención de Salud/estadística & datos numéricos , Complicaciones Posoperatorias , Conductos Biliares/lesiones , Conductos Biliares/cirugía , Factores Económicos , Humanos
3.
Ann Hepatol ; 15(5): 788-94, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27493119

RESUMEN

 We present the case of a 56-yr-old woman with vague abdominal pain of approximately 5 months duration. An ultrasound study showed moderate dilation of the common bile duct. Magnetic resonance cholangiopancreatography confirmed a cystic dilatation of the right hepatic duct with intra and extra hepatic component. The patient underwent right hepatectomy and complete excision of the cyst. Microscopically, the cyst wall was formed by fibrous tissue with mild acute and chronic inflammatory infiltrate, the inner surface showed a single layer of columnar epithelium and extensive squamous metaplasia without atypia, wich expressed p63 and high molecular weight cytoqueratin (34BE12).


Asunto(s)
Quiste del Colédoco , Conducto Hepático Común/anomalías , Dolor Abdominal/etiología , Biomarcadores/análisis , Biopsia , Pancreatocolangiografía por Resonancia Magnética , Quiste del Colédoco/complicaciones , Quiste del Colédoco/diagnóstico por imagen , Quiste del Colédoco/cirugía , Femenino , Hepatectomía , Conducto Hepático Común/química , Conducto Hepático Común/diagnóstico por imagen , Conducto Hepático Común/cirugía , Humanos , Inmunohistoquímica , Queratinas/análisis , Metaplasia , Persona de Mediana Edad , Factores de Transcripción/análisis , Resultado del Tratamiento , Proteínas Supresoras de Tumor/análisis , Ultrasonografía
5.
Rev Invest Clin ; 67(2): 89-97, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25938841

RESUMEN

BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis within the first seven days of transplantation. The frequency of DGF has decreased in the last five years compared with the previous 20 years of the kidney transplant program at a Mexican referral hospital. OBJECTIVE: To determine the incidence and risk factors for DGF in the past five years (2009-2013). METHODS: We analyzed a retrospective cohort of renal transplant recipients from deceased donors at our hospital between March 2009 and May 2013 (Period 2), and compared the results with a previously evaluated cohort (Period 1, between January 1990 and February 2009). RESULTS: During the analyzed period, 78 deceased donor transplants were performed. The frequency of DGF was 9%. Multivariate analysis showed that recipient older age (OR: 1.074419; 95% CI: 1.0009-1.155116; p = 0.05), transoperative amines administration (OR: 7.73; 95% CI: 1.037-57.6; p = 0.046), and hypotension during surgery in the recipient (OR: 11.6; 95% CI: 1.33-100.8; p = 0.026) were risk factors for DGF. CONCLUSION: The incidence of DGF has significantly decreased in the past five years when compared to the previous 20 years in our hospital.


Asunto(s)
Aminas/administración & dosificación , Funcionamiento Retardado del Injerto/epidemiología , Hipotensión/epidemiología , Trasplante de Riñón , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria
6.
HPB (Oxford) ; 17(1): 72-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25212437

RESUMEN

BACKGROUND: Inclusion of the middle hepatic vein (MHV) with a right hepatectomy (RH) in live donor liver transplantation improves venous drainage of the anterior sector of the graft. Its long-term effects on donor left liver (LL) regeneration are not well described. METHODS: Donors who underwent RH with MHV (MHV+, n = 12) were compared with donors who underwent RH with preservation of the MHV (MHV-, n = 24). Peri-operative complications and volume of the entire liver and individual segments were evaluated at 1 year post-donation. RESULTS: There was a trend towards a higher complication rate in the MHV+ group (41% versus 25%), without reaching statistical significance (P = 0.3). Males, high body mass index (BMI) and a smaller residual liver volume (RLV) were predictors for greater LL regeneration. MHV+ donors had impaired regeneration of segment 4 (S4) at 1 year, and compensatory greater left lateral segment regeneration. The absence of venous drainage of S4 (V4) to left hepatic vein (LHV) was a predictor of impaired S4 regeneration. CONCLUSIONS: Regeneration of S4 is impaired in MHV+ donors. Caution should be taken when considering MHV removal on donors with dominant S4, especially on those with potential increased demand for liver regeneration, such as males, higher BMI and a smaller RLV.


Asunto(s)
Hepatectomía , Venas Hepáticas/cirugía , Regeneración Hepática , Trasplante de Hígado/métodos , Hígado/irrigación sanguínea , Hígado/cirugía , Donadores Vivos , Adulto , Índice de Masa Corporal , Femenino , Hepatectomía/efectos adversos , Venas Hepáticas/diagnóstico por imagen , Venas Hepáticas/fisiopatología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Circulación Hepática , Trasplante de Hígado/efectos adversos , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
7.
Rev Invest Clin ; 66(3): 218-24, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25695237

RESUMEN

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.


Asunto(s)
Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Trasplante de Riñón , Receptor de Angiotensina Tipo 1/inmunología , Factores de Edad , Ensayo de Inmunoadsorción Enzimática , Tasa de Filtración Glomerular , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Análisis Multivariante , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes
8.
Transplantation ; 108(2): 464-472, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38259179

RESUMEN

BACKGROUND: Children are removed from the liver transplant waitlist because of death or progressive illness. Size mismatch accounts for 30% of organ refusal. This study aimed to demonstrate that 3-dimensional (3D) technology is a feasible and accurate adjunct to organ allocation and living donor selection process. METHODS: This prospective multicenter study included pediatric liver transplant candidates and living donors from January 2020 to February 2023. Patient-specific, 3D-printed liver models were used for anatomic planning, real-time evaluation during organ procurement, and surgical navigation. The primary outcome was to determine model accuracy. The secondary outcome was to determine the impact of outcomes in living donor hepatectomy. Study groups were analyzed using propensity score matching with a retrospective cohort. RESULTS: Twenty-eight recipients were included. The median percentage error was -0.6% for 3D models and had the highest correlation to the actual liver explant (Pearson's R = 0.96, P < 0.001) compared with other volume calculation methods. Patient and graft survival were comparable. From 41 living donors, the median percentage error of the allograft was 12.4%. The donor-matched study group had lower central line utilization (21.4% versus 75%, P = 0.045), shorter length of stay (4 versus 7 d, P = 0.003), and lower mean comprehensive complication index (3 versus 21, P = 0.014). CONCLUSIONS: Three-dimensional volume is highly correlated with actual liver explant volume and may vary across different allografts for living donation. The addition of 3D-printed liver models during the transplant evaluation and organ procurement process is a feasible and safe adjunct to the perioperative decision-making process.


Asunto(s)
Trasplante de Hígado , Modelos Anatómicos , Niño , Humanos , Hígado , Donadores Vivos , Estudios Prospectivos , Estudios Retrospectivos , Impresión Tridimensional
9.
Lancet Reg Health Am ; 28: 100633, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38058662

RESUMEN

Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.

10.
Clin Transplant ; 26(2): E94-E100, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22211770

RESUMEN

INTRODUCTION: Alagille syndrome (AGS) is an inherited multisystem disorder, and liver transplantation (LT) may be required in pediatric patients with AGS (P-AGS). There are limited data regarding the outcomes of LT in adults with AGS (A-AGS). AIM: To determine and compare the outcomes of LT in A-AGS vs. P-AGS as well as A-AGS vs. adults with biliary atresia (A-BA). METHODS: Adults (>18 yr), with AGS and BA, and children (≤18 yr), with AGS who underwent isolated first LT between 10/1987 and 5/2008, were identified from the UNOS database. RESULTS: Forty-four of 79,400 adults transplanted for AGS were compared with 407 P-AGS and 56 A-BA, respectively. A-AGS patients had a significantly higher rate of encephalopathy, lower serum albumin, and higher serum creatinine in comparison with P-AGS. One- and five-yr patient and graft survival in A-AGS who underwent LT were not significantly different in comparison with either P-AGS or A-BA (A-AGS patient survival: 95.5%, 90.9%, P-AGS: 88. 7%, 86.2%, A-BA: 89.3%, 87.5%; A-AGS graft survival: 84.1%, 79. 5%, P-AGS: 80.3%, 76%. 1%, A-BA: 82.1%, 78.6%, respectively). CONCLUSION: The outcome of first LT in A-AGS is excellent compared with the overall reported adult patient and graft survival. Although A-AGS were sicker than P-AGS at transplant, their outcomes were comparable with that of P-AGS.


Asunto(s)
Síndrome de Alagille/cirugía , Trasplante de Hígado , Adulto , Síndrome de Alagille/complicaciones , Síndrome de Alagille/mortalidad , Atresia Biliar/complicaciones , Atresia Biliar/cirugía , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Masculino , Tasa de Supervivencia
11.
Cir Cir ; 89(2): 269-274, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33784290

RESUMEN

ANTECEDENTES: En diciembre de 2019 se identificó en la ciudad de Wuhan, China, un nuevo beta coronavirus, el SARS-CoV-2, como agente causal de neumonía grave, conocida como COVID-19, lo cual ha provocado medidas estrictas de aislamiento, cierre de programas de trasplante hepático y la necesidad de modificar los protocolos de tratamiento. OBJETIVO: Documentar la información publicada sobre el impacto de la COVID-19 en la población con antecedente de trasplante hepático y establecer un protocolo de tratamiento. MÉTODO: Se buscaron en PubMed los términos MeSH "SARS-CoV-2", "COVID-19", "trasplante hepático" y "tratamiento". RESULTADOS: Hasta el momento se ha demostrado en la población con trasplante hepático una mayor facilidad para adquirir el virus, sin una diferencia en la mortalidad al compararla con la población general. La inmunosupresión debe continuar, sin suspender los inhibidores de la calcineurina. Del tratamiento específico, los esteroides son los que han demostrado el mayor beneficio clínico y una disminución de la mortalidad. CONCLUSIÓN: El trasplante hepático no se asocia de manera independiente a una mayor mortalidad. Otros factores, además del trasplante, deben tomarse en cuenta al momento de establecer la gravedad. BACKGROUND: In December 2019, a new beta coronavirus, SARS-CoV-2, was identified in the city of Wuhan, China, as a causative agent of severe pneumonia, known as COVID-19, which has led to strict isolation measures, closure of liver transplantation programs and the need to modify treatment protocols. OBJECTIVE: Document the information published so far on the impact of COVID-19 in the population with a history of liver transplantation and establish a treatment protocol. METHOD: MeSH terms were searched for "SARS-CoV-2", "COVID-19", "liver transplantation" and "treatment". RESULTS: Up to now, a greater ease in acquiring the virus has been shown in the liver transplant population, without a difference in mortality when compared to the general population. Immunosuppression should continue at the minimum tolerated levels, without suspending calcineurin inhibitors. Of the specific treatment, steroids are those that have shown the greatest clinical benefit and decreased mortality. CONCLUSION: Liver transplantation is not independently associated with higher mortality. Factors other than transplantation must be taken into account when considering the risk of severity.


Asunto(s)
COVID-19/epidemiología , Huésped Inmunocomprometido , Trasplante de Hígado , Pandemias , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Transfusión de Componentes Sanguíneos , COVID-19/terapia , COVID-19/transmisión , Rechazo de Injerto/prevención & control , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Inmunosupresores/administración & dosificación , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Listas de Espera , Privación de Tratamiento , Sueroterapia para COVID-19
12.
Clin Res Hepatol Gastroenterol ; 45(4): 101519, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33636655

RESUMEN

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a risk factor for liver disease. PASD-positive inclusions have been found unexpectedly in approximately 10% of liver explants in patients with no previous diagnosis of AATD, particularly, in patients with non-alcoholic steatohepatitis (NASH), supporting a synergistic mechanism of liver injury between AATD and environmental factors. We aimed to determine the clinical characteristics of mestizo patients in which AATD was diagnosed before or after liver transplantation. METHODS: Liver explants of patients with cryptogenic, alcoholic, and NAFLD/NASH cirrhosis undergoing orthotopic liver transplantation (OLT) were included. Liver histopathology was assessed by two expert pathologists. Hematoxylin and eosin staining, PASD staining, and confirmatory AAT immunohistochemistry were performed. In explants with positive histopathology, genotyping for SERPINA1 was performed. RESULTS: A total of 180 liver transplants were performed during the study period. Of these, 44 patients with cryptogenic cirrhosis, NASH, and alcoholic cirrhosis were included. Of these patients, two liver explants (4.5%) had PASD-positive inclusions stain and confirmatory immunochemistry. During the period evaluated, another two patients with a diagnosis of AATD before the OLT were also included. The four patients had overweight or obesity, three had type 2 diabetes mellitus, and two developed liver steatosis after the OLT. CONCLUSION: AATD was found to be an infrequent finding in patients with cryptogenic, NASH/NAFLD, and alcoholic cirrhosis in our population. However, it is important to consider this entity as it may represent an additional factor in the appearance and progression of liver fibrosis in patients with metabolic syndrome.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Deficiencia de alfa 1-Antitripsina , Humanos , Cirrosis Hepática , Cirrosis Hepática Alcohólica , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Prevalencia , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/epidemiología
13.
J Clin Invest ; 117(12): 3645-8, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18060023

RESUMEN

The development of chronic allograft rejection is based on the hypothesis that cumulative, time-dependent tissue injury eventually leads to a fibrotic response. In this issue of the JCI, Babu and colleagues found that alloimmune-mediated microvascular loss precedes tissue damage in murine orthotopic tracheal allografts (see the related article beginning on page 3774). The concept that injury to the endothelium may precede airway fibrosis suggests that interventions to maintain vascular integrity may be important, especially in the case of lung transplantation. Further, for all solid organ allografts, it is possible that the key to long-term allograft survival is physiological vascular repair at early times following transplantation.


Asunto(s)
Bronquiolitis Obliterante/inmunología , Endotelio Vascular/inmunología , Rechazo de Injerto/inmunología , Trasplante de Pulmón/inmunología , Pulmón/irrigación sanguínea , Fibrosis Pulmonar/inmunología , Animales , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/patología , Bronquiolitis Obliterante/terapia , Endotelio Vascular/patología , Rechazo de Injerto/patología , Rechazo de Injerto/terapia , Supervivencia de Injerto/inmunología , Terapia de Inmunosupresión , Isquemia/inmunología , Isquemia/patología , Pulmón/inmunología , Pulmón/patología , Trasplante de Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Microcirculación/inmunología , Microcirculación/patología , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/terapia , Receptores de Interleucina-8B/inmunología , Síndrome , Factores de Tiempo , Tráquea/irrigación sanguínea , Tráquea/inmunología , Tráquea/patología , Tráquea/trasplante , Trasplante Homólogo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología
14.
J Immunol ; 181(11): 8088-95, 2008 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-19018001

RESUMEN

We have examined CD40-dependent signals in endothelial cells (EC) mediating the expression of vascular endothelial growth factor (VEGF) and VEGF-induced angiogenesis. We treated confluent cultures of EC with soluble CD40L (sCD40L), and by Western blot found a marked increase in the phosphorylation of Akt, 4EBP-1, and S6K1, compared with untreated cells. EC were transfected with a full-length VEGF promoter-luciferase construct and cultured in the absence or presence of rapamycin and sCD40L. We found that rapamycin, which blocks mTORC1 and mTORC2 signaling, inhibited sCD40L-mediated transactivation of VEGF. In addition, by Western blot, we found that the transfection of EC with small interfering RNA (siRNA) to rictor (to inhibit mTORC2), and not raptor (to inhibit mTORC1), inhibited sCD40L-dependent protein expression of VEGF. In additions, we found that basal levels of phosphorylated Akt as well as VEGF were increased in EC transfected with the raptor siRNA. Also, rapamycin failed to inhibit VEGF promoter activation, as well as VEGF protein expression in EC transfected with a constitutively active construct of Akt, further demonstrating that mTORC1 is not necessary for CD40- and Akt-induced expression of VEGF. Finally, we injected human CD40L-transfected fibroblasts or mock transfectants into human skin on SCID mice. We found that the injection of CD40L transfectants, but not mock cells, resulted in VEGF expression and mediated a marked angiogenesis reaction, and this response was reduced in mice treated with rapamycin. Together, these observations indicate that mTORC2 and Akt facilitate CD40-inducible expression of VEGF in EC, which is of clinical importance in tumor growth and the progression of chronic inflammatory diseases.


Asunto(s)
Antígenos CD40/inmunología , Células Endoteliales/inmunología , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal/inmunología , Factores de Transcripción/inmunología , Factor A de Crecimiento Endotelial Vascular/inmunología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Antibacterianos/farmacología , Antígenos CD40/genética , Antígenos CD40/metabolismo , Ligando de CD40/genética , Ligando de CD40/inmunología , Ligando de CD40/metabolismo , Ligando de CD40/farmacología , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Células Endoteliales/metabolismo , Fibroblastos/inmunología , Fibroblastos/metabolismo , Humanos , Inflamación/genética , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Ratones SCID , Complejos Multiproteicos , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/patología , Fosfoproteínas/genética , Fosfoproteínas/inmunología , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Fosforilación/genética , Fosforilación/inmunología , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Regiones Promotoras Genéticas/inmunología , Biosíntesis de Proteínas/efectos de los fármacos , Biosíntesis de Proteínas/genética , Biosíntesis de Proteínas/inmunología , Proteínas/antagonistas & inhibidores , Proteínas/genética , Proteínas/inmunología , Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo
15.
Int J Surg ; 82S: 149-154, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32084547

RESUMEN

Combined liver-kidney transplantation is a life-saving procedure for patients with end-stage liver disease and underlying chronic kidney disease, or prolonged acute kidney injury. Due to physiologic changes secondary to portal hypertension in patients with end-stage liver disease, kidney injury is common, and combined liver-kidney transplantation accounts for 10% of all the liver transplants performed in the United States. Recently implemented policy in the United States standardizes the medical criteria for eligibility, and introduces a 'safety net' for those who are transplanted with a liver graft alone, in order to be able to receive a kidney graft later. Increasing number of combined liver-kidney transplants provides a large cohort of patients to be studied in detail for identification of factors (both donor and recipient-related) associated with better outcomes. Data regarding the safety and efficacy of delaying the kidney transplant part of the combined liver-kidney transplantation, and the immunologic benefits of the multi-organ transplantations including the liver are emerging. Here, we review the most recent analyses, and provide our opinion regarding the best practices in combined liver-kidney transplantation based on the evidence.


Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Riñón , Trasplante de Hígado , Insuficiencia Renal Crónica/cirugía , Enfermedad Hepática en Estado Terminal/etiología , Humanos , Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Insuficiencia Renal Crónica/etiología , Factores de Riesgo
16.
Int J Surg ; 82S: 14-21, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32247089

RESUMEN

The lack of adequate financial coverage, education, and the organization has been the main limiting factor for the development of transplantation in Latin America. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of liver transplantations (LTs) performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in most countries. Access to LT in the region is very heterogeneous. While some countries have no active LT programs so far, others are an international model of a public transplantation system (Brazil) or a national information system (Argentina). While some countries have only a few LT centers, others have too many LT centers performing an inadequate low number of LTs. Disparity to access transplantation remains the major challenge in the region. Cultural and educational efforts have to be accompanied by transparent public policies that will likely increase organ donation and activity in transplantation. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region.


Asunto(s)
Trasplante de Hígado/tendencias , Obtención de Tejidos y Órganos/tendencias , Accesibilidad a los Servicios de Salud/tendencias , Disparidades en Atención de Salud , Humanos , América Latina , Trasplante de Hígado/legislación & jurisprudencia , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/provisión & distribución , Listas de Espera
17.
Transplant Proc ; 52(4): 1102-1105, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32204898

RESUMEN

BACKGROUND: A short right renal vein (RRV) remains a challenge for renal transplant surgery, especially in the living donor. Different techniques exist to obtain an RRV with a suitable length in cadaveric donor; however, in living donors the options are limited. MATERIAL AND METHODS: We present 2 living kidney transplants in which we obtained a very short RRV, making the implantation very difficult. We describe our technique to overcome this problem by using cadaveric iliac vessels retrieved from previous cadaveric donations and preserved at 4°C in histidine-tryptophan-ketoglutarate (HTK) solution, without intraoperative or postoperative complications. We complied with the Helsinki Congress and the Istanbul Declaration regarding the donor source. RESULTS: In both cases, kidney grafts had optimal primary function, with good creatinine clearance after transplant and good patency of vascular anastomosis by Doppler ultrasounds. CONCLUSIONS: We believe the use of cadaveric vessel grafts in living donor kidney transplant is a valuable resource as a rescue tool in emergency situations like the ones being presented in this article in order to avoid discarding a kidney graft with damage or short vessels. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Asunto(s)
Arteria Ilíaca/trasplante , Trasplante de Riñón/métodos , Donadores Vivos , Venas Renales , Aloinjertos , Cadáver , Humanos , Masculino , Persona de Mediana Edad , Trasplante Homólogo
18.
J Am Soc Nephrol ; 19(12): 2437-46, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18832436

RESUMEN

Calcineurin inhibitors (CNI) are used to prevent inflammatory diseases and allograft rejection. However, little is known about the mechanism(s) underlying their ability to promote the development and recurrence of cancer. Recent studies suggested that the chemokine receptor CXCR3 may play important roles in tumorigenesis. CXCR3 has two splice variants with opposite functions: CXCR3-A promotes cell proliferation, and CXCR3-B inhibits cell growth. Here, we explored the effects of CNI on the expression and function of CXCR3 splice variants. Compared with normal renal tissues and renal epithelial cells, human renal cancer tissues and renal cancer cell lines demonstrated higher expression of CXCR3-A and markedly lower expression of CXCR3-B. In human renal cancer cells (786-0 and Caki-1) and renal epithelial cells, CNI markedly downregulated the expression of CXCR3-B, whereas expression of CXCR3-A was unchanged. This CNI-mediated downregulation of CXCR3-B resulted in increased proliferation and migration of renal cancer cells; CNI-mediated cell proliferation involved signaling through G(i) proteins, perhaps via CXCR3-A. Finally, it was observed that CNI treatment increased the growth of human renal tumors in vivo, and the expression of CXCR3-B was significantly decreased in these tumors. In summary, these observations suggest that CNI may mediate the progression of human renal cancer by downregulating CXCR3-B and by promoting proliferative signals, likely through CXCR3-A. Targeting CXCR3 splice variants or the signaling pathways downstream of CXCR3 receptors may provide a therapeutic strategy for the prevention of CNI-mediated renal cancer progression.


Asunto(s)
Calcineurina/farmacología , Regulación de la Expresión Génica , Neoplasias Renales/metabolismo , Receptores CXCR3/antagonistas & inhibidores , Receptores CXCR3/fisiología , Empalme Alternativo , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Transducción de Señal , Cicatrización de Heridas
19.
Transpl Immunol ; 54: 1-8, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30336216

RESUMEN

The association between anti-AT1Rabs and microvascular injury observed in antibody-mediated rejection has been described in kidney graft Biopsies (KGBx). METHODS: We herein describe the histopathologic findings of KGBx performed during the first year of transplantation (Tx) in 134 patients tested for pre-Tx anti-AT1Rabs in cryopreserved sera (04/2009 to 09/2013). Protocol KGBx before implantation (time-zero), 1 year after Tx and for cause KGBx were included. 21/134 Tx patients were anti-AT1Rab positive (≥17 U/mL); 7/21 experienced acute rejection. For comparison a control group with anti-AT1Rabs <17 U/mL, with (n = 16) and without (n = 31) acute rejection was included. RESULTS: Preimplantation KGBx showed no differences in inflammatory and chronic findings, nor in subintimal fibrosis (25 vs 12.8%, p = .42) between patients with anti-AT1Rabs ≥17 U/mL and those with <17 U/mL. Follow-up KGBx revealed a significantly greater proportion of arterial sub-intimal fibrosis (52.3 vs. 27.6%, p = .049) and extension (15.7 vs. 5.3, p = .015) in anti-AT1Rabs ≥17 U/mL compared to anti-AT1Rabs <17 U/mL KGBx. No differences were observed in microcirculation inflammation, nor in interstitial fibrosis or tubular atrophy between groups. Also, anti-AT1Rabs ≥17 U/mL (ß 10.1, 2.3 to 17.8, p = .012) and more importantly anti-AT1Rabs ≥ 30 U/mL (ß12.1, 3.1 to 20.9, p < .01), were independent risk factors associated with vascular occlusion resulting from sub-intimal fibrosis. CONCLUSION: Our study findings have shown that anti-AT1Rab values ≥17 U/mL are significantly associated to sub-intimal fibrosis and a greater percentage of vessel occlusion in kidney graft biopsies obtained during the first year posttransplant, particularly in coexistence with inflammation and de novo DSA.


Asunto(s)
Aloinjertos/patología , Oclusión de Injerto Vascular/epidemiología , Rechazo de Injerto/inmunología , Trasplante de Riñón , Riñón/patología , Receptor de Angiotensina Tipo 1/inmunología , Túnica Íntima/patología , Adolescente , Adulto , Aloinjertos/irrigación sanguínea , Anticuerpos/sangre , Femenino , Fibrosis , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Humanos , Riñón/irrigación sanguínea , Donadores Vivos , Masculino , México/epidemiología , Receptores de Trasplantes , Adulto Joven
20.
J Endocr Soc ; 3(3): 537-543, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30788455

RESUMEN

Doege-Potter syndrome with acromegaloid facial changes is extremely rare. Uncooked cornstarch along with glucocorticoids have been used as supportive care in patients with non-islet cell tumor hypoglycemia (NICTH). Preoperative embolization of hepatic solitary fibrous tumors (SFT) with NICTH has yielded unsatisfactory results. Herein we present the case of a 61-year-old man with a 3-month history of severe frequent hypoglycemic episodes and acromegaloid facial changes. During a spontaneous hypoglycemia (26 mg/dL), laboratory values showed a hypoinsulinemic pattern with low levels of GH, IGFPB3, and an IGF2/IGF1 ratio of 8.5:1. Cross-sectional imaging revealed a large (16 × 13 × 11 cm) hepatic tumor, and cytology was consistent with SFT. A preoperative right portal embolization was performed in an effort to induce normal remnant liver hypertrophy to allow for safe tumor resection. After the procedure, uncooked starch treatment followed by prednisone was started, achieving complete remission of hypoglycemic episodes in the preoperative setting. He subsequently underwent partial hepatectomy. The histologic diagnosis was compatible with a potentially malignant SFT. The patient had an excellent outcome with complete remission of hypoglycemia, improvement of facial acromegaloid changes, and no further evidence of disease. To our knowledge, this is the first case of a patient with Doege-Potter syndrome with acromegaloid facial changes induced by a potentially malignant liver SFT, treated successfully with a multimodal approach consisting of uncooked cornstarch, low-dose prednisone, preoperative embolization, and complete surgical resection. The use of cornstarch and low-dose glucocorticoids may be an adequate treatment in advance of undergoing surgery.

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