RESUMEN
There is a critical need to understand the disease processes and identify improved therapeutic strategies for hepatocellular carcinoma (HCC). The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. The aim of this study was to identify a lncRNA as a potential biomarker of HCC and investigate the mechanisms by which the lncRNA promotes HCC progression using human cell lines and in vivo. Using RNA-Seq analysis, we found that lncRNA FIRRE was significantly upregulated in hepatitis C virus (HCV) associated liver tissue and identified that lncRNA FIRRE is significantly upregulated in HCV-associated HCC compared to adjacent non-tumor liver tissue. Further, we observed that FIRRE is significantly upregulated in HCC specimens with other etiologies, suggesting this lncRNA has the potential to serve as an additional biomarker for HCC. Overexpression of FIRRE in hepatocytes induced cell proliferation, colony formation, and xenograft tumor formation as compared to vector-transfected control cells. Using RNA pull-down proteomics, we identified HuR as an interacting partner of FIRRE. We further showed that the FIRRE-HuR axis regulates cyclin D1 expression. Our mechanistic investigation uncovered that FIRRE is associated with an RNA-binding protein HuR for enhancing hepatocyte growth. Together, these findings provide molecular insights into the role of FIRRE in HCC progression.
Asunto(s)
Carcinoma Hepatocelular , Ciclina D1 , Proteína 1 Similar a ELAV , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , ARN Largo no Codificante , Transducción de Señal , Animales , Humanos , Ratones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/metabolismo , Ciclina D1/genética , Proteína 1 Similar a ELAV/metabolismo , Proteína 1 Similar a ELAV/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Ratones Desnudos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/genética , Hepatitis C/complicaciones , Regulación hacia Arriba , Biomarcadores de TumorRESUMEN
Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.
Asunto(s)
Cirugía Bariátrica , Obesidad , Trasplante de Órganos , Humanos , Obesidad/complicaciones , Obesidad/cirugía , Trasplante de Órganos/efectos adversos , Receptores de TrasplantesRESUMEN
Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however, it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A), or TPN + intraduodenal fecal microbiota transplant (TPN + FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16 s rRNA sequencing. Permutational multivariate analysis of variance, Jaccard, and Bray-Curtis metrics were performed. Significant bilirubin elevation in TPN and TPN-A versus EN (P < 0.0001) was prevented with FMT. IFN-G, TNF-α, IL-ß, IL-8, and lipopolysaccharide (LPS) were significantly higher in TPN (P = 0.009, P = 0.001, P = 0.043, P = 0.011, P < 0.0001), with preservation upon FMT. Significant gut atrophy by villous-to-crypt ratio in TPN (P < 0.0001) and TPN-A (P = 0.0001) versus EN was prevented by FMT (P = 0.426 vs. EN). Microbiota profiles using principal coordinate analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN-altered gut barrier was preserved upon FMT; upregulated cholesterol 7 α-hydroxylase and bile salt export pump in TPN and TPN-A and downregulated fibroblast growth factor receptor 4, EGF, farnesoid X receptor, and Takeda G Protein-coupled Receptor 5 (TGR5) versus EN was prevented by FMT. This study provides novel evidence of prevention of gut atrophy, liver injury, and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores the importance of gut microbes as prime targets for therapeutics and drug discovery.NEW & NOTEWORTHY Intraduodenal fecal microbiota transplantation presents a novel strategy to mitigate complications associated with total parenteral nutrition (TPN), highlighting gut microbiota as a prime target for therapeutic and diagnostic approaches. These results from a highly translatable model provide hope for TPN side effect mitigation for thousands of chronically TPN-dependent patients.
Asunto(s)
Colestasis , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Nutrición Parenteral Total , Animales , Trasplante de Microbiota Fecal/métodos , Porcinos , Colestasis/terapia , Colestasis/microbiología , Nutrición Parenteral Total/métodos , Atrofia , Modelos Animales de Enfermedad , Hígado/patología , Hígado/metabolismoRESUMEN
BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Riñón , Humanos , Hepacivirus , Antivirales/uso terapéutico , Trasplante de Riñón/efectos adversos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hepatitis C/cirugía , Hepatitis C/etiología , Donantes de Tejidos , RiñónRESUMEN
Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.
Asunto(s)
Cirugía Bariátrica , Obesidad , Trasplante de Órganos , Humanos , Cirugía Bariátrica/métodos , Obesidad/cirugía , Obesidad/complicacionesRESUMEN
BACKGROUND: Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. METHODS: Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. RESULTS: Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. CONCLUSION: PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.
Asunto(s)
Ferroptosis , Trasplante de Hígado , Hígado/irrigación sanguínea , Perfusión/métodos , Daño por Reperfusión/prevención & control , Selección de Donante , Supervivencia de Injerto , Humanos , Técnicas In Vitro , Pruebas de Función Hepática , Preservación de Órganos/métodosRESUMEN
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is one of the major causal factors for hepatocellular carcinoma (HCC). The treatment options for HCC are limited for lack of a convenient animal model for study in HCV infection and liver pathogenesis. This study aimed to develop a patient-derived xenograft (PDX) tumor in mice by using a tumor from a patient with HCV-associated HCC and evaluating this model's therapeutic potential. APPROACH AND RESULTS: After resection of the primary tumor from the patient liver, excess viable tumor was implanted into highly immunodeficient mice. A mouse xenograft tumor line was developed, and the tumor was successfully passaged for at least three rounds in immunodeficient mice. The patient's primary tumor and the mouse xenografts were histologically similar. Genetic profiling by short-tandem-repeat analysis verified that the HCC-PDX model was derived from the HCC clinical specimen. HCV RNA present in the patient liver specimen was undetectable after passage as xenograft tumors in mice. Human albumin, α1 -antitrypsin, glypican-3, α-smooth muscle actin, and collagen type 1A2 markers were detected in human original tumor tissues and xenograft tumors. Both the patient primary tumor and the xenograft tumors had a significantly higher level of receptor tyrosine kinase (c-Kit) mRNA. Treatment of HCC-PDX xenograft tumor-bearing mice with the c-Kit inhibitor imatinib significantly reduced tumor growth and phospho-Akt and cyclin D1 expression, as compared with untreated control tumors. CONCLUSIONS: Our results demonstrated establishment of an HCV-associated HCC-PDX model as a powerful tool for evaluating candidate drugs. Information on molecular changes in cancer-specific gene expression facilitates efficient targeted therapies and treatment strategies.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Modelos Animales de Enfermedad , Hepatitis C Crónica/complicaciones , Xenoinjertos , Mesilato de Imatinib/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Trasplante de Neoplasias , Animales , Humanos , Ratones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The use of Hepatitis C (HCV) NAT positive allografts remains unusual and is clustered at few centers. We conducted a contemporary literature review to assess whether patient and clinician attitudes toward viremic organs impact acceptance. METHODS: Databases including PubMed, MEDLINE, and SCOPUS databases were reviewed to identify studies focused on evaluating patient and provider perceptions of HCV NAT positive organ use within the DAA era (January 2015-April 2021). Search included MeSH terms related to Hepatitis C, transplantation, and patient and clinician attitudes. Two investigators extracted study characteristics including information on willingness to accept viremic organs, HCV-specific outcomes knowledge, HCV-specific concerns, and factors that contributed to acceptance or non-acceptance. RESULTS: Eight studies met all inclusion criteria. These included three pretransplant patient-directed studies, two post-transplant patient-directed studies, one pre- and post-transplant patient-directed study, and two clinician-directed studies. Common themes identified were concerns regarding HCV cure rates, viremic organ quality, DAA cost, stigma, and the possibility of HCV transmission to household members. The perception of decreased waitlist time was associated with viremic organ acceptance. Physician trust played a mixed role in acceptance patterns. CONCLUSIONS: Knowledge of high cure rates, shorter waitlist times, and higher organ quality appear to have the highest impact on organ acceptance.
Asunto(s)
Antivirales , Hepatitis C , Antivirales/uso terapéutico , Actitud , Hepacivirus , Hepatitis C/tratamiento farmacológico , Humanos , Donantes de TejidosRESUMEN
To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Rechazo de Injerto/prevención & control , Trasplante de Riñón/métodos , Medicina de Precisión/métodos , Inducción de Remisión/métodos , Adulto , Anticuerpos Monoclonales Humanizados/farmacología , Estudios de Cohortes , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Obtención de Tejidos y Órganos/organización & administración , Inmunología del Trasplante , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described. METHODS: We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ≥ 23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. RESULTS: The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension. CONCLUSION: Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Trasplante de Riñón/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Accidentes/estadística & datos numéricos , Reclamos Administrativos en el Cuidado de la Salud , Adolescente , Adulto , Alcoholismo/epidemiología , Arritmias Cardíacas/epidemiología , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Paro Cardíaco/epidemiología , Humanos , Hipercapnia/epidemiología , Hipotensión/epidemiología , Incidencia , Donadores Vivos , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Periodo Preoperatorio , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Biliary intraepithelial neoplasm (BilIN) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are recognized as the two main precursors to biliary carcinoma. Surgical resection is the mainstay of treatment, with pancreaticoduodenectomy for extrahepatic biliary duct disease involving the pancreatic or distal portion of the bile duct, and bile duct and liver resection for perihilar and intrahepatic bile duct involvement. For diffuse IPMN-B with involvement of the entirety of the biliary epithelium of both intrahepatic and extrahepatic biliary systems, there is no well-documented consensus on treatment due to its rarity. Therefore, we present a case of a 56-year-old male with diffuse IPMN-B managed with combined orthotopic liver transplant and pancreaticoduodenectomy. As such, the clinical presentation, diagnostics, and unique course of intervention for our patient are described. This case provides insight into the topic of managing IPMN-Bs, particularly with diffuse biliary tree involvement. With such a rare disease with wildly varied presentations, consensus on a set treatment algorithm is nearly impossible to establish. This case describes one treatment pathway we found to be successful.
RESUMEN
The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.
RESUMEN
BACKGROUND: Homozygosity for LIMS1 rs893403-GG genotype is linked to an increased risk of allograft rejection after kidney transplantation. Ischemia-reperfusion of the kidney allograft leads to long term infiltration of activated and effector-memory T lymphocytes and resulting in rejection and long-term fibrosis. However, the genotype, LIMS1 expression under ischemic conditions and the long-term histopathological relationships remain ill-defined. METHODS: We examined the impact of the recipient's LIMS1-rs893403 genotype with transplant kidney histopathology. The association of the LIMS1-rs893403 genotype and LIMS1 and GCC2 mRNA expression in ischemic donor kidneys were also examined. Recipients who underwent transplant kidney biopsy were genotyped for the LIMS1-rs893403 variant and associated deletion. Histopathological findings were compared between recipients with LIMS1 risk and non-risk genotypes. Real-time PCR and immunofluorescence staining for LIMS1 and GCC2 expression were performed in non-utilized donor kidneys. RESULTS: Demographic, clinical, and treatment characteristics and the histopathological diagnosis were similar between recipients with rs893403 GG and AA/AG genotype. The Banff tubulitis score was higher in GG recipients (n = 24) compared to AA/AG (n = 86) recipients (1.42 ± 0.65 vs. 1.12 ± 0.66, p = 0.03). Ischemic kidneys with GG showed higher LIMS1 and GCC2 mRNA expression than kidneys with AG. Kidneys with rs893403-GG had higher tubular LIMS1 and GCC2 immunohistochemical staining compared to kidneys with rs893403-AG. CONCLUSIONS: Our data supports the role of the LIMS1 locus in kidney transplant rejection, particularly in lymphocyte infiltration into the internal aspect of the tubular basement membranes. Increased LIMS1 and GCC2 expression in ischemic donor kidneys with the GG genotype require further studies.
Asunto(s)
Genotipo , Trasplante de Riñón , Túbulos Renales , Proteínas con Dominio LIM , Trasplante de Riñón/efectos adversos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Proteínas con Dominio LIM/genética , Túbulos Renales/patología , Túbulos Renales/metabolismo , Inflamación/genética , Inflamación/patología , Rechazo de Injerto/genética , Rechazo de Injerto/patología , Polimorfismo de Nucleótido SimpleRESUMEN
In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.
Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Riñón/cirugía , Riñón/fisiología , Preservación de Órganos/métodos , Donantes de Tejidos , Perfusión/métodosRESUMEN
PURPOSE: Although over 90% of the population of the United States supports organ donation, only 60% of the population is registered as donors. Currently, there is a need for a nonmonetary incentive that will improve willingness to donate. We assessed the young adult population's perspective on their willingness to donate organs when merit points are granted to their family members to prioritize their potential transplant if needed. METHODS: We administered a Qualtrics survey from March 2022 to September 2022 to the undergraduate students volunteering to participate at Saint Louis University, which comprised 10 questions that addressed the attitudes of participants regarding the effects of various factors, including the type of donation and the presence of merit points (vouchers granted to self or a family member to facilitate a potential transplant if needed), on participant's willingness to donate an organ while alive or after death. The responses were analyzed by using SAS software (SAS Institute). RESULTS: A total of 572 participants completed the survey. Overall, only 6.5% of surveyed students were unwilling to donate after death. The willingness to donate while alive to a family member was significantly higher than donating to a stranger (95.8% vs 71.2%, P < .0001). When merit points were added, the unwillingness to donate significantly decreased from 6.5% to 3.8%. However, this change was observed only when the merit points were given to a family member and not to self. When merit points were granted, unwillingness to provide a living donation to a stranger decreased from 28.8% to 16.4% (P < .0001). CONCLUSIONS: Merit points to first-degree family members improve students' expressed willingness to donate organs after death; however, self-merit points did not decrease the rate of "unwillingness to donate after death." When living donation is assessed, offering merit points appears to decrease the "unwillingness to donate to strangers." The adoption of a merit point system in the United States may increase the rates of organ donation.
Asunto(s)
Trasplante de Órganos , Obtención de Tejidos y Órganos , Adulto Joven , Humanos , Motivación , Donantes de Tejidos , Actitud , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Extrahepatic malignancies are a relatively rare incidental finding during liver transplant work-up that provides a significant barrier to continued transplant evaluation and requires treatment to limit the risk of recurrence. There have only been 11 previously reported cases of pre-liver transplant renal cell carcinoma (RCC), of which all underwent partial or radical nephrectomy. Percutaneous cryoablation therapy has been gaining acceptance as a curative treatment alternative for RCC and is a new therapeutic standard for patients who are poor candidates for surgical resection. Recent studies have demonstrated the safety and efficacy of cryoablation for RCC in native kidneys and in solid masses in kidney allografts, but there is no data on the efficacy or recurrence of RCC when cryoablation is used for the treatment of RCC in a native kidney prior to solid organ transplantation. The patient underwent percutaneous cryoablation therapy of a T1a RCC of the native kidney 10 months prior to orthotopic liver transplant (OLT) without subsequent partial or radical nephrectomy. At seven years post-ablation therapy, the patient has no evidence of tumor recurrence despite immunosuppressive therapy post-transplantation. Cryoablation is potentially a safe and highly effective means of treating RCC in patients who are not candidates for nephrectomy secondary to complications associated with end-stage liver disease. In our case, the patient was treated with cryoablation and received standard post-transplant immunosuppression without recurrence of RCC at seven years. More studies are needed to determine inclusion and exclusion criteria for cryoablation and to confirm long-term efficacy as well as a strategy for duration and frequency of surveillance in these patients.
RESUMEN
Adrenal rest tumors are rare collections of aberrantly located adrenocortical tissue. They are most commonly found in the kidneys, and hepatic involvement is rare with few published case reports. When located in the liver, imaging findings are frequently indistinguishable from hepatocellular carcinoma (HCC), but when resected, histologic examination shows adrenocortical tissue. Here, we present a patient with a history of nonalcoholic steatohepatitis with advanced fibrosis who was identified as having HCC by cross-sectional imaging but was found to have a hepatic adrenal rest tumor (HART) after resection. HARTs can share imaging characteristics with HCC, and this alternative diagnosis should be considered, especially for hepatic segment VII lesions.
RESUMEN
Ehrlichia infection has a broad spectrum of diseases ranging from asymptomatic to fatal. While Ehrlichia often presents as a mild form of the disease in immunocompetent patients, immunosuppressed patients are at increased risk for a more virulent and potentially fatal infection. Our liver transplant patient presented with fever, persistent headaches, and negative Ehrlichia antibodies. Empiric antibiotic therapy was started and along with knowledge of prior tick infection, doxycycline was added. Subsequent positive PCR and observation of Ehrlichia chaffeensis in peripheral blood smear confirmed the diagnosis. The patient did recover from infection but not before it manifested in hepatic, renal, and pulmonary involvement. Therefore, a high level of suspicion is necessary for early detection and treatment initiation to prevent a devastating progression of the disease in immunosuppressed patients.
RESUMEN
Liver transplantation is currently the only curative treatment for patients with end-stage liver disease. However, liver transplantation can be associated with catastrophic complications in the early postoperative setting, including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT). Postoperative complications are associated with hepatic artery resistive index (RI) < 6, systolic acceleration time (SAT) > 0.08 seconds and peak systolic velocity (PSV) > 200 cm/s on doppler ultrasound (DUS). DUS is also used in an intraoperative setting to assess patency and early complications prior to the end of the operative period, allowing for early correction. This literature review evaluates the prevalence of DUS use in intraoperative settings to identify transplant complications. A lack of consistency and minimal knowledge of intraoperative DUS warrants additional research into its usage and standardization.