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1.
J Vasc Interv Radiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969336

RESUMO

PURPOSE: To test the hypothesis that Pressure Enabled Drug Delivery (PEDD) with a TriNav device (TNV-21120-35, TriSalus Life Sciences, Westminster, CO) would improve the delivery of surrogate therapeutic glass microspheres (GM) via hepatic artery infusion (HAI) to liver tumors when compared to a conventional endhole microcatheter. MATERIALS AND METHODS: The study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a TriNav device was compared to conventional endhole delivery in both lobar and selective infusions. Near-Infrared (nearIR) imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom Deep Learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. RESULTS: With lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n=10) when compared to conventional delivery (n=7), with PEDD increasing penetration into the tumor by 117% (p = 0.004). In selective infusions, PEDD (n=9) increased penetration into the tumor by 39% relative to conventional delivery (n=8, p =0.032). Lobar PEDD delivery of GM to the tumor was statistically equivalent to conventional selective delivery (p=0.497). CONCLUSIONS: PEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.

2.
J Vasc Interv Radiol ; 31(11): 1740-1744.e9, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33019993

RESUMO

Advances in immunotherapy have changed the landscape of oncology over the past decade. Still, most patients with solid organ tumors do not derive a durable benefit from immunotherapies. How these tumors evade treatment has not been fully elucidated, but several studies are seeking ways to stimulate treatment response in these immunologically quiescent tumors. Of these, the combination of locoregional therapy with immune checkpoint inhibition is of interest to the interventional radiologist. This brief report provides an overview of current trials testing the effectiveness of locoregional therapy in combination with immune checkpoint inhibitors and identifies future research goals.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Embolização Terapêutica , Neoplasias/terapia , Antineoplásicos Imunológicos/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Humanos , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/patologia , Resultado do Tratamento
3.
Am J Med Genet A ; 179(3): 410-416, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30672094

RESUMO

We report three patients with Feingold 2 syndrome with the novel features of growth hormone deficiency associated with adenohypophyseal compression, aortic dilation, phalangeal joint contractures, memory, and sleep problems in addition to the typical features of microcephaly, brachymesophalangy, toe syndactyly, short stature, and cardiac anomalies. Microdeletions of chromosome 13q that include the MIR17HG gene were found in all three. One of the patients was treated successfully with growth hormone. In addition to expanding the phenotype of Feingold 2 syndrome, we suggest management of patients with Feingold 2 syndrome include echocardiography at the time of diagnosis in all patients and consideration of evaluation for growth hormone deficiency in patients with short stature.


Assuntos
Aorta/anormalidades , Cognição , Pálpebras/anormalidades , Estudos de Associação Genética , Hormônio do Crescimento Humano/deficiência , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Microcefalia/diagnóstico , Microcefalia/genética , Fenótipo , Fístula Traqueoesofágica/diagnóstico , Fístula Traqueoesofágica/genética , Anormalidades Múltiplas , Adulto , Idoso , Feminino , Estudos de Associação Genética/métodos , Gráficos de Crescimento , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia
5.
J Vasc Interv Radiol ; 30(3): 298-304.e2, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819469

RESUMO

PURPOSE: To retrospectively assess the efficacy and safety of radioembolization with yttrium-90 (90Y) resin microspheres as a second-line option in patients with liver metastases from pancreatic adenocarcinoma. MATERIALS AND METHODS: Thirty-three patients with metastatic pancreatic adenocarcinoma that progressed despite systemic chemotherapy and other treatments directed at primary tumors and metastases were treated with 90Y radioembolization at 1 of 3 institutions from 2011 through 2017. Data from laboratory and imaging studies at 2, 4, 8, and 12 weeks after treatment were analyzed. Tumor response was assessed with Response Evaluation Criteria In Solid Tumors version 1.1 and adverse events with Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Imaging results showed partial response in 8 patients (42%), stable disease in 7 (37%), and progressive disease in 4 (21%). Median overall survival times after radioembolization and diagnosis of the primary tumor were 8.1 (95% CI, 4.8-12.5) and 20.8 (95% CI, 14.2-29.0) months, respectively. Radioembolization did not produce major hepatic toxicity, and changes in liver enzyme levels were rarely grade ≥ 3 during the 12-week follow-up. The exceptions were 3 patients with grade 3 increased alkaline phosphatase (week 2) and bilirubin levels (week 4), increased bilirubin level (week 12), and decreased albumin level (week 12), respectively. Most reported complications were grade ≤ 2, with 2 patients showing short-term radioembolization-related grade 3 abdominal distention, abdominal pain, fatigue, or ascites. CONCLUSIONS: Yttrium-90 radioembolization provided a meaningful survival benefit in patients with liver metastases from pancreatic adenocarcinoma that progressed despite previous therapies. Adverse events and liver toxicity were tolerable and only occasionally severe (grade ≥ 3).


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Radioisótopos de Ítrio/efeitos adversos
6.
J Vasc Interv Radiol ; 30(7): 995-1003, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109853

RESUMO

PURPOSE: To evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation. MATERIALS AND METHODS: An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test. RESULTS: Before transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence. CONCLUSIONS: Poor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Transplante de Fígado , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Carga Tumoral
7.
J Vasc Interv Radiol ; 29(3): 307-310.e1, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29455874

RESUMO

In 17 patients who underwent prostate artery embolization for treatment of lower urinary tract symptoms, the accuracy of preprocedural magnetic resonance (MR) angiography was retrospectively compared with intraprocedural digital subtraction angiography (DSA) in the identification of prostatic artery origin. Of 34 vessels, 26 MR angiography identified origins (76.5%) were confirmed by DSA at the time of embolization. Although image postprocessing is required, the ability of MR angiography to accurately identify prostatic artery origins prior to embolization is useful in treatment planning and can obviate the need for separate computed tomographic angiography, thus reducing both radiation dose and time demand on patients.


Assuntos
Embolização Terapêutica/métodos , Sintomas do Trato Urinário Inferior/diagnóstico por imagem , Sintomas do Trato Urinário Inferior/terapia , Angiografia por Ressonância Magnética/métodos , Próstata/irrigação sanguínea , Angiografia Digital/métodos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
9.
BMC Cancer ; 16: 492, 2016 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-27430276

RESUMO

BACKGROUND: The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with systemic chemotherapy in the treatment of liver-dominant metastatic pancreatic ductal adenocarcinoma, with the aim of destroying liver metastases and improving patient outcomes. METHODS: We retrospectively evaluated 16 patients with liver-dominant metastatic pancreatic ductal adenocarcinoma who underwent TARE between February 2012 and August 2015; 15 of these patients also underwent concurrent systemic chemotherapy. Patient outcomes were assessed using Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1 and included disease response, median overall survival from the time of diagnosis of metastatic disease, and median overall survival following receipt of TARE. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. RESULTS: The median overall survival from the time of diagnosis of metastatic disease and following receipt of TARE was 22.0 and 12.5 months, respectively. Overall and liver specific disease response were assessed for 13 patients with follow-up imaging available at the time of study (range 2-13 weeks post TARE). Four patients (31 %) demonstrated partial response and five patients (38 %) had stable disease in the liver at follow-up. One patient developed grade 3 elevation of total bilirubin three months post-treatment and another patient developed radiation cholecystitis directly following TARE. No treatment-related grade 4 or 5 toxicities were seen. CONCLUSION: TARE can be safely combined with systemic chemotherapy for the treatment of liver-dominant metastatic pancreatic cancer. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.


Assuntos
Carcinoma Ductal Pancreático/terapia , Ablação por Cateter/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pancreáticas/terapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Ítrio/uso terapêutico
10.
Curr Med Res Opin ; 40(4): 591-598, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38414420

RESUMO

OBJECTIVES: Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. METHODS: This study used a retrospective, longitudinal, cohort design of claims data from Clarivate's Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. RESULTS: PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. CONCLUSION: Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Estudos Retrospectivos , Resultado do Tratamento , Radioisótopos de Ítrio/uso terapêutico , Quimioembolização Terapêutica/efeitos adversos
11.
Ann Gastroenterol Surg ; 7(2): 295-305, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36998293

RESUMO

Background and Aims: In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach: We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results: Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions: An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.

12.
Ther Adv Rare Dis ; 3: 26330040221093743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37180415

RESUMO

Introduction: Barth syndrome (BTHS) is a rare X-linked disorder characterized by cardiomyopathy, neutropenia, growth abnormalities, and skeletal myopathy. There have been few studies investigating health-related quality of life (HRQoL) in this population. This study investigated the impact of BTHS on HRQoL and select physiologic measures in affected boys and men. Methods: In this study, we characterize HRQoL in boys and men with BTHS through cross-sectional analysis of a variety of outcome measures including the Pediatric Quality of Life Inventory (PedsQLTM) Version 4.0 Generic Core Scales, PedsQLTM Multidimensional Fatigue Scale, Barth Syndrome Symptom Assessment, the PROMISTM Fatigue Short Form, the EuroQol Group EQ-5DTM, the Patient Global Impression of Symptoms (PGIS), and the Caregiver Global Impression of Symptoms (CaGIS). For a specific subset of participants, physiologic data were available in addition to HRQoL data. Results: For the PedsQLTM questionnaires, 18 unique child and parent reports were analyzed for children aged 5-18 years, and nine unique parent reports were analyzed for children aged 2-4 years. For the other HRQoL outcome measures and physiologic measurements, the data from 12 subjects (age range 12-35 years) were analyzed. Based on parent and child reports, HRQoL is significantly impaired in boys and men with BTHS, especially in school functioning and physical functioning. Parent and child reports of more severe fatigue are significantly correlated with more impaired HRQoL. When exploring the potential relationship between physiology and HRQoL, the CaGIS as a whole for pediatric subjects and individual questionnaire items from the PGIS and CaGIS for pediatric subjects assessing tiredness, muscle weakness, and muscle pain showed the strongest correlations. Conclusion: This study provides a unique characterization of the HRQoL in boys and men with BTHS using a variety of outcome measures, and it highlights the negative impact of fatigue and muscle weakness on HRQoL in BTHS. Trial registry name: A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects with Barth Syndrome (TAZPOWER). https://clinicaltrials.gov/ct2/show/NCT03098797.Registration Number: NCT03098797.


Quality of Life in Barth Syndrome Barth syndrome is a rare disorder characterized by heart issues, muscle weakness, tiredness, exercise intolerance, and growth delays. The study was done to determine the effect of Barth syndrome on health-related quality of life of the boys and men affected. We analyzed health-related quality of life questionnaires completed by subjects and/or their parents from the following: • Interdisciplinary Barth Syndrome Clinic at Kennedy Krieger Institute. There were 24 subjects in total from this clinic. • Baseline data from a clinical drug trial for Barth Syndrome that included both health-related quality of life data and physical function data. There were data from 12 subjects in total from the trial. We discovered that health-related quality of life is significantly impaired in boys and men with Barth syndrome, especially in school and physical function. Parent and child reports of more severe tiredness are significantly linked with impaired health-related quality of life. There are strong relationships between some health-related quality of life reports and physical function measurements. Tiredness and muscle weakness negatively impact health-related quality of life. We are hopeful that the results of this study will be used in the treatment of boys and men with Barth syndrome to result in improved health-related quality of life.

13.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32709737

RESUMO

Establishing the diagnosis of hereditary fructose intolerance (HFI) remains difficult despite the availability of specific molecular genetic testing of the ALDOB gene. This is attributable, at least in part, to the lack of a specific and practical biomarker. We report the incidental diagnosis of HFI as a consequence of nontargeted genetic testing ordered for alternative indications in 5 patients, including 3 children and 2 adults. Two of the children were diagnosed with HFI after extensive evaluations that ultimately involved clinical or research exome sequencing. The third child was diagnosed with HFI during subsequent genetic testing of at-risk family members. Both adults learned to avoid fructose and remained asymptomatic of HFI before diagnosis. One was diagnosed with HFI during preconception, nontargeted expanded carrier screening. For the other, concern for HFI was initially raised by indeterminate direct-to-consumer genetic testing results. None of these patients presented with infantile acute liver failure or other acute decompensation. Our findings suggest that the emphasis of classic teaching on infantile liver failure after first exposure to fructose may be inadvertently increasing the likelihood of missing cases of HFI characterized by other manifestations. HFI is likely underdiagnosed and should be considered for patients with nonspecific findings as well as for individuals with significant aversion to sweets.


Assuntos
Intolerância à Frutose/diagnóstico , Adulto , Idoso , Doenças Assintomáticas , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Triagem e Testes Direto ao Consumidor , Nanismo/genética , Insuficiência de Crescimento/genética , Feminino , Preferências Alimentares , Intolerância à Frutose/genética , Frutose-Bifosfato Aldolase/genética , Frutas/efeitos adversos , Testes Genéticos , Humanos , Achados Incidentais , Infertilidade Feminina , Masculino , Cuidado Pré-Concepcional , Verduras/efeitos adversos , Sequenciamento do Exoma
14.
Animal Model Exp Med ; 3(1): 98-102, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32318666

RESUMO

The most commonly used preclinical models of hepatocellular carcinoma (HCC) are limited for use in testing of intra-arterial therapies such as transarterial chemoembolization and radioembolization. Issues encountered with the more commonly used animal models include dissimilarity in their disease development compared with humans and the size of the vasculature which can make intra-arterial therapy testing difficult or impossible. Here we describe the suitability of the woodchuck HCC model for testing of intra-arterial therapies. We describe the techniques for pre-embolization imaging assessment using CT and MRI, technical tips on performing angiography and embolization, and pathological assessment of treated liver.

15.
JIMD Rep ; 51(1): 17-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32071835

RESUMO

Cobalamin C (cblC) deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in MMACHC and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late-onset cblC may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated. We report three adult siblings with late-onset cblC disease, and their biochemical and clinical responses to high-dose hydroxocobalamin. The 28-year-old proband presented with severe psychosis, progressive neurological deterioration, and deep venous thrombosis complicated by a pulmonary embolism. MRI studies identified lesions in the spinal cord, periventricular white matter, and basal ganglia. Serum homocysteine and methylmalonic acid levels were markedly elevated. Hydroxocobalamin at standard dose (1 mg/day) initially resulted in partial metabolic correction. A regimen of high-dose hydroxocobalamin (25 mg/day) together with betaine and folic acid resulted in rapid and sustainable biochemical correction, resolution of psychosis, improvement of neurological functions, and amelioration of brain and spinal cord lesions. Two siblings who did not manifest neuropsychiatric symptoms or thromboembolism achieved a satisfactory metabolic control with the same high-dose regimen. Hydroxocobalamin injection was then spaced out to 25 mg weekly with good and sustainable metabolic control. All three patients are compound heterozygotes for c.271dupA p.Arg91LysfsX14 and c.389A > G p.Tyr130Cys. This study highlights the importance of evaluating intracellular cobalamin metabolism in adults with neuropsychiatric manifestations and/or thromboembolic events, and demonstrates that high-dose hydroxocobalamin achieves rapid and sustainable metabolic control and improvement in neuropsychiatric outcomes in adults with late-onset cblC disease.

16.
J Radiol Case Rep ; 13(2): 34-42, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31565170

RESUMO

Trans-radial access offers several unique advantages and is being used more frequently for interventional radiology procedures. We report the use of trans-radial arterial access to embolize a large bleeding angiomyolipoma in a 30-year-old pregnant patient presenting in the first trimester. Trans-radial approach was chosen to minimize the effects of radiation on the fetus. Subsequent postprocedural pregnancy course was uneventful with stability of the angiomyolipoma and no further hemorrhage. This case highlights the benefits of trans-radial embolotherapy in gravid patients to reduce the risk of radiation exposure to the fetus.


Assuntos
Angiomiolipoma/complicações , Embolização Terapêutica/métodos , Hemorragia/etiologia , Hemorragia/terapia , Neoplasias Renais/complicações , Complicações Neoplásicas na Gravidez/terapia , Adulto , Angiografia Digital , Angiomiolipoma/diagnóstico por imagem , Feminino , Fluoroscopia , Hemorragia/diagnóstico por imagem , Humanos , Neoplasias Renais/diagnóstico por imagem , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Artéria Radial , Tomografia Computadorizada por Raios X , Ultrassonografia
17.
Expert Rev Med Devices ; 15(2): 99-106, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29307242

RESUMO

INTRODUCTION: Irreversible electroporation (IRE) has developed as a novel percutaneous ablative technique over the past decade and its utility in the treatment of primary and metastatic liver disease has progressed rapidly. AREAS COVERED: After discussing the principles behind the technology and the practical steps in its use, this article offers a detailed analysis of the recent published work that evaluates its safety and efficacy. The strengths and weaknesses of other ablative techniques, including radiofrequency ablation, microwave ablation and cryoablation, are discussed in detail. Other aspects of IRE, including post-treatment clinical follow-up, expected imaging findings, and the most frequently encountered complications, are covered. Finally, the future of IRE is examined as it pertains to advancements in the treatment of hepatic malignancy. EXPERT COMMENTARY: The characteristics of IRE that make this technology uniquely suited for the treatment of liver tumors have allowed it to gain a significant foothold in interventional oncology. Continued development of IRE will lead to further advances in the management of previously untreatable liver cancers.


Assuntos
Eletroporação/métodos , Neoplasias Hepáticas/cirurgia , Técnicas de Ablação , Humanos , Neoplasias Hepáticas/diagnóstico por imagem
18.
Cardiovasc Intervent Radiol ; 41(12): 1857-1866, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30006891

RESUMO

PURPOSE: To compare the use of cone-beam computed tomography versus contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) in the calculation of liver volume and planned dose for yttrium-90 radioembolization. MATERIALS AND METHODS: The study retrospectively assessed 47 consecutive patients who underwent resin Y-90 radioembolization consecutively over a 2-year period at a single center. Volume calculation software was used to determine perfused lobar liver volumes from cone-beam CT (CBCT) images obtained during mapping angiography. CBCT-derived volumes were compared with perfused lobar volume derived from contrast-enhanced CT and MRI. Nominal activities as determined by the SIR-Spheres Microspheres Activity Calculator were similarly calculated and compared using both CBCT and conventionally acquired volumes. RESULTS: A total of 82 hepatic lobes were assessed in 47 patients. The mean percentage difference between combined CT-MRI- and CBCT-derived calculated lobar volumes was 25.3% (p = 0.994). The mean percentage difference in calculated dose between the two methods was 21.8 ± 24.6% (p = 0.42). Combined left and right lobar CT-derived dose difference was less than 10% in 22 lobes, between 10 and 25% in 20 lobes, between 25 and 50% in 13 lobes and greater than 50% in 5 lobes. Combined left and right lobar MRI-derived dose difference was less than 10% in 11 lobes, between 10 and 25% in 7 lobes, between 25 and 50% in 2 lobes and greater than 50% in 1 lobe. CONCLUSIONS: Although volume measurements derived from CT/MRI did not differ significantly from those derived from CBCT, variability between the two methods led to large and unexpected differences in calculated dose.


Assuntos
Braquiterapia/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Hepáticas/radioterapia , Imageamento por Ressonância Magnética/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/efeitos da radiação , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Tamanho do Órgão , Dosagem Radioterapêutica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
19.
Mol Cell Biol ; 22(11): 3729-43, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11997509

RESUMO

Aberrant expression of PU.1 inhibits erythroid cell differentiation and contributes to the formation of murine erythroleukemias (MEL). The molecular mechanism by which this occurs is poorly understood. Here we show that PU.1 specifically and efficiently inhibits CBP-mediated acetylation of several nuclear proteins, including the hematopoietic transcription factors GATA-1, NF-E2, and erythroid Krüppel-like factor. In addition, PU.1 blocks acetylation of histones and interferes with acetylation-dependent transcriptional events. CBP acetyltransferase activity increases during MEL cell differentiation as PU.1 levels decline and is inhibited by sustained PU.1 expression. Finally, PU.1 inhibits the differentiation-associated increase in histone acetylation at an erythroid-specific gene locus in vivo. Together, these findings suggest that aberrant expression of PU.1 and possibly other members of the Ets family of oncoproteins subverts normal cellular differentiation in part by inhibiting the acetylation of critical nuclear factors involved in balancing cellular proliferation and maturation.


Assuntos
Proteínas Nucleares/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/antagonistas & inibidores , Transativadores/metabolismo , Células 3T3 , Acetilação , Animais , Diferenciação Celular , Divisão Celular , Linhagem Celular , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Ligação de DNA Eritroide Específicos , Fator de Transcrição GATA1 , Globinas/genética , Histonas/metabolismo , Camundongos , Fator de Transcrição NF-E2 , Subunidade p45 do Fator de Transcrição NF-E2 , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Transativadores/química , Fatores de Transcrição/metabolismo , Ativação Transcricional
20.
PLoS One ; 12(9): e0183861, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28863147

RESUMO

PURPOSE: To review the initial imaging responses after drug-eluting embolic trans-arterial chemoembolization (DEE-TACE) delivered with the Surefire Infusion System ® for the treatment of hepatocellular carcinoma (HCC). METHODS: Single center retrospective evaluation of patients who underwent DEE-TACE for HCC, delivered with SIS. Information was gathered from available medical records. Treatment response rates were assessed using the modified Response Evaluation Criteria in Solid Tumors criteria. Assessment of adverse events was categorized per Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Twenty-two patients with 39 hepatocellular carcinoma lesions were treated with the surefire infusion system. Complete response was demonstrated in 32% of patients and 54% of lesions after a single treatment session. Overall disease response was demonstrated in 91% of patients and 85% of lesions after a single treatment. No grade 3 or higher elevations in liver function tests were demonstrated in the short-term. CONCLUSION: SIS delivered DEE-TACE leads to a higher than expected initial response in patients with HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Stents Farmacológicos , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Diagnóstico por Imagem/métodos , Doxorrubicina/administração & dosagem , Registros Eletrônicos de Saúde , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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