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1.
J Biol Chem ; 300(5): 107247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556083

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Ciclina D1 , Proteína Semelhante a ELAV 1 , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , RNA Longo não Codificante , Transdução de Sinais , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Ciclina D1/genética , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Camundongos Nus , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Hepatite C/complicações , Regulação para Cima , Biomarcadores Tumorais
2.
Am J Transplant ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38951053

RESUMO

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.

3.
Clin Transplant ; 38(1): e15161, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37842872

RESUMO

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.


Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Rim , Humanos , Hepacivirus , Antivirais/uso terapêutico , Transplante de Rim/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia , Hepatite C/etiologia , Doadores de Tecidos , Rim
4.
Surg Endosc ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951240

RESUMO

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.

5.
Pediatr Transplant ; 26(2): e14164, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34633130

RESUMO

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.


Assuntos
Ferroptose , Transplante de Fígado , Fígado/irrigação sanguínea , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Seleção do Doador , Sobrevivência de Enxerto , Humanos , Técnicas In Vitro , Testes de Função Hepática , Preservação de Órgãos/métodos
6.
Hepatology ; 72(2): 379-388, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32356575

RESUMO

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.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Modelos Animais de Doenças , Hepatite C Crônica/complicações , Xenoenxertos , Mesilato de Imatinib/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Transplante de Neoplasias , Animais , Humanos , Camundongos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Clin Transplant ; 35(12): e14519, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34672392

RESUMO

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.


Assuntos
Antivirais , Hepatite C , Antivirais/uso terapêutico , Atitude , Hepacivirus , Hepatite C/tratamento farmacológico , Humanos , Doadores de Tecidos
9.
Transpl Int ; 31(2): 198-211, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28987015

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/métodos , Medicina de Precisão/métodos , Indução de Remissão/métodos , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Estudos de Coortes , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Obtenção de Tecidos e Órgãos/organização & administração , Imunologia de Transplantes , Resultado do Tratamento , Estados Unidos , Adulto Jovem
10.
Am J Nephrol ; 41(2): 165-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25832723

RESUMO

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.


Assuntos
Analgésicos Opioides/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Transplante de Rim/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Acidentes/estatística & dados numéricos , Demandas Administrativas em Assistência à Saúde , Adolescente , Adulto , Alcoolismo/epidemiologia , Arritmias Cardíacas/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Parada Cardíaca/epidemiologia , Humanos , Hipercapnia/epidemiologia , Hipotensão/epidemiologia , Incidência , Doadores Vivos , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Período Pré-Operatório , Estados Unidos/epidemiologia , Adulto Jovem
11.
Genes (Basel) ; 15(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927709

RESUMO

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.


Assuntos
Genótipo , Transplante de Rim , Túbulos Renais , Proteínas com Domínio LIM , Transplante de Rim/efeitos adversos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteínas com Domínio LIM/genética , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Inflamação/genética , Inflamação/patologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Polimorfismo de Nucleotídeo Único
12.
Int J Artif Organs ; 46(12): 618-628, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897367

RESUMO

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.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Rim/cirurgia , Rim/fisiologia , Preservação de Órgãos/métodos , Doadores de Tecidos , Perfusão/métodos
13.
Transplant Proc ; 55(10): 2326-2332, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925234

RESUMO

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.


Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Adulto Jovem , Humanos , Motivação , Doadores de Tecidos , Atitude , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
14.
Cureus ; 14(12): e32531, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36654550

RESUMO

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.

15.
Cureus ; 14(11): e31343, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36514652

RESUMO

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.

16.
Case Rep Transplant ; 2022: 3062836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722444

RESUMO

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.

17.
Cureus ; 14(6): e26077, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35865449

RESUMO

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.

18.
Nutrients ; 14(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364922

RESUMO

Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut-brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.


Assuntos
Síndrome do Intestino Curto , Animais , Humanos , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/terapia , Síndrome do Intestino Curto/metabolismo , Modelos Animais de Doenças , Nutrição Parenteral Total , Intestino Delgado/metabolismo , Fígado/metabolismo
19.
J Vasc Surg ; 54(2): 529-32, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21397438

RESUMO

Takayasu's arteritis is a rare form of aortic vasculitis, typically described in young Asian females. In this article, we report a unique presentation of type V Takayasu's arteritis in a Hispanic male. To the best of our knowledge, this is the first case of Takayasu's arteritis presenting with the triad of angina, amaurosis fugax, and subclavian steal syndrome. On diagnostic imaging, he was found to have left subclavian and axillary artery stenosis requiring balloon angioplasty. The patient responded to the combination of medical and surgical treatment with full recovery.


Assuntos
Amaurose Fugaz/etiologia , Angina Pectoris/etiologia , Síndrome do Roubo Subclávio/etiologia , Arterite de Takayasu/diagnóstico , Vertigem/etiologia , Corticosteroides/uso terapêutico , Adulto , Amaurose Fugaz/terapia , Angina Pectoris/terapia , Angioplastia com Balão , Aortografia , Humanos , Angiografia por Ressonância Magnética , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome do Roubo Subclávio/terapia , Arterite de Takayasu/complicações , Arterite de Takayasu/terapia , Resultado do Tratamento , Vertigem/terapia
20.
Am J Ther ; 18(6): e258-60, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20335786

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction leading to organ dysfunction. Drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome has been recognized for several years. The most commonly implicated drugs are mitomycin C, cyclosporine, quinine, clopidogrel, and ticlopidine. Recent advances have suggested that like in idiopathic TTP, the most likely pathogenesis for drug-induced TTP is either an immune-mediated phenomenon involving the ADAMTS13 metalloprotease or direct endothelial toxicity. In this communication, we report a case of micafungin-induced TTP. Micafungin is a new antifungal drug of the Echinocandins group. Whether micafungin induces autoantibodies against ADAMTS13 or not, this needs further evaluation, but TTP should be recognized as a possible complication of micafungin. Clinicians should be alert to this adverse effect of micafungin and monitor platelet counts in patients receiving this drug.


Assuntos
Antifúngicos/efeitos adversos , Equinocandinas/efeitos adversos , Lipopeptídeos/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Proteínas ADAM/imunologia , Proteínas ADAM/fisiologia , Proteína ADAMTS13 , Antifúngicos/imunologia , Autoanticorpos , Equinocandinas/imunologia , Humanos , Lipopeptídeos/imunologia , Masculino , Micafungina , Púrpura Trombocitopênica Trombótica/imunologia , Púrpura Trombocitopênica Trombótica/fisiopatologia , Adulto Jovem , Fator de von Willebrand/fisiologia
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