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1.
Radiology ; 311(2): e231386, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713023

RESUMO

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microesferas , Radioisótopos de Ítrio , Humanos , Masculino , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Radioisótopos de Ítrio/uso terapêutico , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
2.
Hepatology ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557474

RESUMO

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. International normalized ratio testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and diagnostic endosopies. For the other procedures examined, the risks outweigh benefits when platelet count is >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the periprocedural management of coagulopathy in cirrhosis.

3.
Acta Pharmacol Sin ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519646

RESUMO

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.

4.
J Am Coll Radiol ; 21(5): 721-728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38220041

RESUMO

PURPOSE: The aim of this study is to uncover potential areas for cost savings in uterine artery embolization (UAE) using time-driven activity-based costing, the most accurate costing methodology for direct health care system costs. METHODS: One hundred twenty-three patients who underwent outpatient UAE for fibroids or adenomyosis between January 2020 and December 2022 were retrospectively reviewed. Utilization times were captured from electronic health record time stamps and staff interviews using validated techniques. Capacity cost rates were estimated using institutional data and manufacturer proxy prices. Costs were calculated using time-driven activity-based costing for personnel, equipment, and consumables. Differences in time utilization and costs between procedures by an interventional radiology attending physician only versus an interventional radiology attending physician and trainee were additionally performed. RESULTS: The mean total cost of UAE was $4,267 ± $1,770, the greatest contributor being consumables (51%; $2,162 ± $811), followed by personnel (33%; $1,388 ± $340) and equipment (7%; $309 ± $96). Embolic agents accounted for the greatest proportion of consumable costs, accounting for 51% ($1,273 ± $789), followed by vascular devices (15%; $630 ± $143). The cost of embolic agents was highly variable, driven mainly by the number of vials (range 1-19) of tris-acryl gelatin particles used. Interventional radiology attending physician only cases had significantly lower personnel costs ($1,091 versus $1,425, P = .007) and equipment costs ($268 versus $317, P = .007) compared with interventional radiology attending physician and trainee cases, although there was no significant difference in mean overall costs ($3,640 versus $4,386; P = .061). CONCLUSIONS: Consumables accounted for the majority of total cost of UAE, driven by the cost of embolic agents and vascular devices.


Assuntos
Leiomioma , Embolização da Artéria Uterina , Humanos , Feminino , Embolização da Artéria Uterina/economia , Estudos Retrospectivos , Leiomioma/terapia , Leiomioma/economia , Leiomioma/diagnóstico por imagem , Adulto , Radiologia Intervencionista/economia , Pessoa de Meia-Idade , Neoplasias Uterinas/terapia , Neoplasias Uterinas/economia , Neoplasias Uterinas/diagnóstico por imagem , Custos de Cuidados de Saúde/estatística & dados numéricos , Redução de Custos , Radiografia Intervencionista/economia
5.
Nucl Med Commun ; 45(3): 175-180, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38165160

RESUMO

OBJECTIVES: To determine if three new simplified equations for measurement of free mebrofenin clearance give similar results to the equations defined by Ekman et. al ., and to evaluate the properties of all four methods. Regional mebrofenin clearance has been used to predict future remnant liver function and liver failure after regional liver therapy, such as partial hepatic resection. METHODS: The means, standard deviations, and correlations of the free mebrofenin clearance measured by the Ekman method and the three simplified methods were compared in a consecutive series of 26 studies in 20 patients. The fractional change in the blood and free mebrofenin activities were compared, and integrals of normalized blood and free mebrofenin ("effective times") were compared. RESULTS: The average percent free mebrofenin clearance for the Ekman and the first, second and third simplified methods were 13.62 ± 2.88%/min, 12.98 ± 2.97%/min, 12.52 ± 2.81%/min and 15.03 ± 2.27%/min, respectively. The correlations of the new methods with Ekman were 0.97, 0.93 and 0.93. The fractional changes during the measurement interval for the blood and free mebrofenin activities were 0.381 ± 0.065 and 0.329 ± 0.062, difference 0.052, P < 0.5. The integrals of normalized blood and free mebrofenin activities were 2.566 ± 0.160 min and 2.661 ± 0.158 min, difference of 0.094 min and P < 0.05. CONCLUSIONS: The results of the three new methods were similar to the Ekman method. The first simplified method was identified as the lead method for clinical validation in a larger population.


Assuntos
Glicina , Fígado , Compostos de Organotecnécio , Humanos , Cintilografia , Testes de Função Hepática , Compostos de Anilina , Iminoácidos
6.
J Adv Res ; 58: 193-210, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37271476

RESUMO

INTRODUCTION: Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody-drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. OBJECTIVES: To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. METHODS: Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. RESULTS: Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/ß-catenin positive loop, in which the Trop2/ß-catenin complex prevented ß-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized ß-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. CONCLUSIONS: These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing ß-catenin in Trop2/ß-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.


Assuntos
Neoplasias da Mama , Quassinas , Animais , Humanos , Feminino , Neoplasias da Mama/patologia , Transdução de Sinais , Linhagem Celular Tumoral , beta Catenina/genética , beta Catenina/metabolismo , Retroalimentação , Modelos Animais de Doenças
7.
J Vasc Interv Radiol ; 35(1): 102-112.e5, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37696431

RESUMO

PURPOSE: To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items. RESULTS: Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment. CONCLUSIONS: HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Idoso , Estados Unidos/epidemiologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Medicare , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Pessoal de Saúde , Análise de Sistemas , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente , Pesquisas sobre Atenção à Saúde
8.
Clin Anat ; 37(2): 185-192, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37638802

RESUMO

The purpose of this study is to compare the subjective and objective quality and confidence between conventional angiography with cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) for the preoperative evaluation of potential donors for living donor liver transplant. Seventeen patients undergoing preoperative donor evaluation for living donor liver transplantation that underwent angiography with CBCT and contrast-enhanced MRI for evaluation of hepatic vascular anatomy were included in the study. Four attending radiologists interpreted anonymized, randomized angiography with CBCT images and MRIs, rating the diagnostic quality and confidence of their interpretation (on a 3-point scale) for each element, as well as clinically relevant measurements. Overall, the readers rated the quality of angiography with CBCT to be higher than that of MRI (median [interquartile range] = 3 (2, 3) vs. 2 (1-3), p < 0.001) across all patients. Readers of angiography with CBCT had more confidence in their interpretations as an average of all elements evaluated than the MRI readers (3 (3) vs. 3 (2, 3), p < 0.001). When the same reader interpreted both MRI and CBCT, the right hepatic artery diameter (3.8 mm ± 0.72 mm vs. 4.5 mm ± 1.2 mm, p < 0.005) and proper hepatic artery diameter (4.43 mm ± 0.98 mm vs. 5.4 mm ± 1.05 mm, p < 0.003) were significantly different between MRI and CBCT. There was poor interrater reliability for determining segment IV arterial supply for both modalities (κ < 0.2). Angiography with CBCT provides higher subjective diagnostic quality and greater radiologist confidence than MRI. The difference in measurements between CBCT and MRI when the same reader reads both studies suggests CBCT adds additional information over MRI evaluation alone.


Assuntos
Transplante de Fígado , Humanos , Doadores Vivos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética , Angiografia , Tomografia Computadorizada de Feixe Cônico/métodos
9.
J Pharm Pharmacol ; 75(10): 1294-1309, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37463100

RESUMO

OBJECTIVES: Pancreatic cancer (PC) is a very lethal malignancy with a scarcity of treatment options. Although erlotinib- and gemcitabine-based treatments have been approved for PC, their effectiveness is limited. The present study is aimed at exploring the molecular and epigenetic mechanisms of anticancer activities of homoharringtonine (HHT) and its interaction with erlotinib to develop a potential therapeutic strategy for PC. METHODS: The RT-qPCR, western blotting, immunofluorescence and expression-vectors and oligonucleotide transfection were employed to determine the expression characteristics of onco-factors. Anticancer activities were determined by MTT, colony forming, and flowcytometric analysis. Dual luciferase assay was conducted to confirm putative target of miR-130b-3p. In-vivo experiments were followed by immunohistochemical assay. KEY FINDINGS: The EphB4/JAK2/STAT3 pathway drives the growth and proliferation of PC through induction of prosurvival factors and cell cycle mediators. HHT directly and epigenetically via miR-130b-3p targets EphB4, leading to downregulation of JAK2/STAT3 pathway. The inactivation of STAT3 results in diminution of antiapoptotic factors and cell cycle mediators. HHT also enhances the anticancer activity of erlotinib. CONCLUSIONS: HHT demonstrates potential anticancer activities in PC by downregulating EphB4/JAK2/STAT3 signalling. HHT also produces synergistic effects with erlotinib.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , Mepesuccinato de Omacetaxina/farmacologia , MicroRNAs/metabolismo , Cloridrato de Erlotinib/farmacologia , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proliferação de Células , Janus Quinase 2/metabolismo , Janus Quinase 2/farmacologia , Fator de Transcrição STAT3/metabolismo , Neoplasias Pancreáticas
10.
J Vasc Interv Radiol ; 34(8): 1337-1344, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37187437

RESUMO

PURPOSE: To evaluate the ability of hand motion analysis using conventional and new motion metrics to differentiate between operators of varying levels of experience for central venous access (CVA) and liver biopsy (LB). MATERIALS AND METHODS: In the CVA task, 7 interventional radiologists (experts), 10 senior trainees, and 5 junior trainees performed ultrasound-guided CVA on a standardized manikin; 5 trainees were retested after 1 year. In the LB task, 4 radiologists (experts) and 7 trainees biopsied a lesion on a manikin. Conventional motion metrics (path length and task time), a refined metric (translational movements), and new metrics (rotational sum and rotational movements) were calculated. RESULTS: In the CVA task, experts outperformed trainees on all metrics (P < .02). Senior trainees required fewer rotational movements (P = .02), translational movements (P = .045), and time (P = .001) than junior trainees. Similarly, on 1-year follow-up, trainees had fewer translational (P = .02) and rotational (P = .003) movements with less task time (P = .003). The path length and rotational sum were not different between junior and senior trainees or for trainees on follow-up. Rotational and translational movements had greater area under the curve values (0.91 and 0.86, respectively) than the rotational sum (0.73) and path length (0.61). In the LB task, experts performed the task with a shorter path length (P = .04), fewer translational (P = .04) and rotational (P = .02) movements, and less time (P < .001) relative to the trainees. CONCLUSIONS: Hand motion analysis using translational and rotational movements was better at differentiating levels of experience and improvement with training than the conventional metric of path length.


Assuntos
Benchmarking , Internato e Residência , Humanos , Mãos , Ultrassonografia , Competência Clínica , Ultrassonografia de Intervenção
11.
J Vasc Interv Radiol ; 34(8): 1373-1381.e3, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37182668

RESUMO

PURPOSE: To report the safety and effectiveness of transjugular intrahepatic portosystemic shunt and mechanical thrombectomy (TIPS-thrombectomy) for symptomatic acute noncirrhotic portal vein thrombosis (NC-PVT). MATERIALS AND METHODS: Patients with acute NC-PVT who underwent TIPS-thrombectomy between 2014 and 2021 at a single academic medical center were retrospectively reviewed. Thirty-two patients were included (men, 56%; median age, 51 years [range, 39-62 years]). The causes for PVT included idiopathic (n = 12), prothrombotic disorders (n = 11), postsurgical sequelae (n = 6), pancreatitis (n = 2), and Budd-Chiari syndrome (n = 1). The indications for TIPS-thrombectomy included refractory abdominal pain (n = 14), intestinal venous ischemia (n = 9), ascites (n = 4), high-risk varices (n = 3), and variceal bleeding (n = 2). Variables studied included patient, disease, and procedure characteristics. Patients were monitored over the course of 1-year follow-up. RESULTS: Successful recanalization of occluded portal venous vessels occurred in all 32 patients (100%). Compared with pretreatment patency, recanalization with TIPS-thrombectomy resulted in an increase in patent veins (main portal vein [28% vs 97%, P < .001], superior mesenteric vein [13% vs 94%, P < .001], and splenic vein [66% vs 91%, P < .001]). Three procedure-related adverse events occurred (Society of Interventional Radiology grade 2 moderate). Hepatic encephalopathy developed in 1 (3%) of 32 patients after TIPS placement. At 1-year follow-up, return of symptoms occurred in 3 (9%) of 32 patients: (a) ascites (n = 1), (b) variceal bleeding (n = 1), and (c) intestinal venous ischemia (n = 1). The intention-to-treat 1-year portal vein and TIPS primary and secondary patency rates were 78% (25/32) and 100% (32/32), respectively. Seven patients required additional procedures, and the 1-year mortality rate was 3% (1/32). CONCLUSIONS: TIPS-thrombectomy is a safe and effective method for treating patients with symptomatic acute NC-PVT.


Assuntos
Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática , Varizes , Trombose Venosa , Masculino , Humanos , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Varizes Esofágicas e Gástricas/etiologia , Ascite/diagnóstico por imagem , Ascite/etiologia , Ascite/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Gastrointestinal/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Trombectomia/efeitos adversos , Varizes/etiologia , Isquemia
13.
Biochem Pharmacol ; 213: 115618, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37211172

RESUMO

The host stimulator of interferon genes (STING) signaling pathway is a major innate immune sensing pathway, and the stimulation of this pathway within antigen-presenting cells shows promise in targeting immune-suppressed tumors. Macrophages resident in tumors exhibit anti-inflammatory properties and enhance tumor growth and development. Polarizing such macrophages towards a pro-inflammatory phenotype is an effective strategy for tumor suppression. In the present study, we observed that the STING pathway was inactivated in breast and lung carcinomas, and a positive correlation existed between STING and macrophage markers in these tumors. We found that vanillic acid (VA) could stimulate the STING/TBK1/IRF3 pathway. VA mediated the production of type I IFN and promoted macrophage polarization into the M1 phenotype; this activity was dependent on STING activation. A direct-contact co-culture model and a transwell co-culture model revealed that macrophages with VA-induced STING activation exhibited anti-proliferative effects on SKBR3 and H1299 cells, although a STING antagonist and M2 macrophage-related cytokines alleviated this anti-proliferative effect. Further investigation indicated that phagocytosis and apoptosis-inducing effects were the major mediators of the anti-tumor effect of VA-treated macrophages. Mechanistically, VA promoted the polarization of macrophages to a M1 phenotype via IL-6R/JAK signaling, resulting in enhanced phagocytosis and apoptosis-induction effects. Additionally, STING activation-induced IFNß production also participated in the apoptosis mediated by VA-treated macrophage in SKBR3 and H1299 cells. Mouse models with 4 T1 tumors confirmed the anti-tumor properties of VA in vivo and revealed the infiltration of VA-induced cytotoxic T cells into the tumors. These data suggest that VA is an effective agonist of STING and provides a new perspective for cancer immunotherapy.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismo , Neoplasias Pulmonares/metabolismo , Macrófagos , Fagocitose , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Ácido Vanílico/metabolismo , Humanos
14.
Hepatol Commun ; 7(4)2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36972387

RESUMO

BACKGROUND AIMS: Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE. APPROACH: We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019. The primary outcome was overall survival from the date of the first TACE treatment, and the primary exposure of interest was Barcelona Clinic Liver Cancer stage migration to a more advanced stage within 6 months of TACE. Survival analysis was completed using Kaplan-Meier and multiple Cox proportional hazard models adjusted by the site. RESULTS: Of 651 eligible patients (51.9% Barcelona Clinic Liver Cancer stage A and 39.6% stage B), 129 (19.6%) patients experienced stage migration within 6 months of TACE. Those with stage migration had larger tumors (5.6 vs. 4.2 cm, p < 0.01) and higher AFP levels (median 92 vs. 15 ng/mL, p < 0.01). In multivariate analysis, stage migration was significantly associated with worse survival (HR: 2.82, 95% CI: 2.66-2.98), with a median survival of 8.7 and 15.9 months in those with and without stage migration. Other predictors of worse survival included the White race, higher AFP levels, a higher number of tumors, and a larger maximum HCC diameter. CONCLUSION: Stage migration is associated with increased mortality after TACE in patients with HCC and could serve as a surrogate end point in clinical trials evaluating locoregional therapies such as TACE.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Adulto , Humanos , Estudos Retrospectivos , alfa-Fetoproteínas/análise , Estadiamento de Neoplasias
15.
J Vasc Interv Radiol ; 34(7): 1115-1125.e17, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36898665

RESUMO

PURPOSE: To systematically review cost research in interventional radiology (IR) published since the Society of Interventional Radiology Research Consensus Panel on Cost in December 2016. MATERIALS AND METHODS: A retrospective assessment of cost research in adult and pediatric IR since December 2016 to July 2022 was conducted. All cost methodologies, service lines, and IR modalities were screened. Analyses were reported in a standardized fashion to include service lines, comparators, cost variables, analytical processes, and databases used. RESULTS: There were 62 studies published, with most from the United States (58%). Incremental cost-effectiveness ratio, quality-adjusted life-years, and time-driven activity-based costing (TDABC) analyses were performed in 50%, 48%, and 10%, respectively. The most frequently reported service line was interventional oncology (21%). No studies on venous thromboembolism, biliary, or IR endocrine therapies were found. Cost reporting was heterogeneous owing to varying cost variables, databases, time horizons, and willingness-to-pay (WTP) thresholds. IR therapies were more cost-effective than their non-IR counterparts for treating hepatocellular carcinoma ($55,925 vs $211,286), renal tumors ($12,435 vs $19,399), benign prostatic hyperplasia ($6,464 vs $9,221), uterine fibroids ($3,772 vs $6,318), subarachnoid hemorrhage ($1,923 vs $4,343), and stroke ($551,159 vs $577,181). TDABC identified disposable costs contributing most to total IR costs: thoracic duct embolization (68%), ablation (42%), chemoembolization (30%), radioembolization (80%), and venous malformations (75%). CONCLUSIONS: Although much of the contemporary cost-based research in IR aligned with the recommendations by the Research Consensus Panel, gaps remained in service lines, standardization of methodology, and addressing high disposable costs. Future steps include tailoring WTP thresholds to nation and health systems, cost-effective pricing for disposables, and standardizing cost sourcing methodology.


Assuntos
Radiologia Intervencionista , Adulto , Humanos , Criança , Análise Custo-Benefício , Consenso , Estudos Retrospectivos
16.
AJR Am J Roentgenol ; 221(2): 249-257, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36946897

RESUMO

BACKGROUND. A major cause of burnout is moral distress: when one knows the right course of action but institutional constraints make the right course impossible to pursue. OBJECTIVE. The purpose of this study was to assess the frequency and severity with which radiologists experience moral distress and to explore moral distress's root causes and countermeasures. METHODS. This study entailed a national survey that evaluated moral distress in radiology. The survey incorporated the validated Moral Distress Scale for Health Care Professionals, along with additional questions. After the scale was modified for applicability to radiology, respondents were asked to assess 16 clinical scenarios in terms of frequency and severity of moral distress. On May 10, 2022, the survey was sent by e-mail to 425 members of radiology practices included on a national radiology society's quality-and-safety LISTSERV. The Measure of Moral Distress for Health Care Professionals (MMD-HP) score was calculated for each respondent as a summary measure of distress across scenarios (maximum possible score, 256). RESULTS. After 12 surveys with incomplete data were excluded, the final analysis included 93 of 425 respondents (22%). A total of 91 of 93 respondents (98%) experienced at least some moral distress for at least one scenario. A total of 17 of 93 respondents (18%) had left a clinical position due to moral distress; 26 of 93 (28%) had considered leaving a clinical position due to moral distress but did not leave. The mean MMD-HP score was 73 ± 51 (SD) for those who had left, 89 ± 47 for those who had considered leaving but did not leave, and 39 ± 35 for those who had never considered leaving (p < .001). A total of 41 of 85 respondents (48%) thought that the COVID-19 pandemic had influenced their moral distress level. Across respondents, the three scenarios with highest moral distress were related to systemic causes (higher case volume than could be read safely, high case volume preventing teaching residents, and lack of administrative action or support). The countermeasure most commonly selected to alleviate moral distress was educating leadership about sources of moral distress (71%). CONCLUSION. Moral distress is prevalent in radiology, typically relates to systemic causes, and is a reported contributor to radiologists changing jobs. CLINICAL IMPACT. Urgent action by radiology practice leadership is required to address moral distress, as radiologists commonly practice in environments contradictory to their core values as physicians.


Assuntos
COVID-19 , Médicos , Radiologia , Humanos , Pandemias , Princípios Morais , Inquéritos e Questionários , Estresse Psicológico/etiologia
18.
Clin Transl Sci ; 16(3): 524-535, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36601684

RESUMO

Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID-19). Conventional meta-analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID-19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID-19. We evaluated the overall treatment group effect by log-likelihood ratio test (-2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (-2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614-1.610; -2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta-analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome-coronavirus 2 viral clearance and COVID-19 hospitalization did not show a clinical benefit of HCQ. Our meta-analysis provides evidence to support the interruption in the use of HCQ in mild COVID-19 outpatients to reduce progression to severe disease.


Assuntos
COVID-19 , Adulto , Humanos , Tratamento Farmacológico da COVID-19 , Hidroxicloroquina , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
J Vasc Interv Radiol ; 34(3): 351-356, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36521795

RESUMO

PURPOSE: To assess technical feasibility and safety of portal vein thrombectomy with suction thrombectomy using a large-bore thrombectomy device for portomesenteric venous thrombosis (PMVT). MATERIALS AND METHODS: After receiving approval from institutional review board, patients undergoing PMVT treatment using a large-bore aspiration thrombectomy device (Inari FlowTriever or ClotTriever) between July 2019 and June 2021 were identified at 2 medical centers. Charts were reviewed for demographic information, imaging findings, and procedural details. PMVT was categorized using the Yerdel grading system. The thrombectomy procedure was performed via transjugular access through the existing or a new transjugular intrahepatic portosystemic shunt (TIPS) or transsplenic or transhepatic approach. Technical success was defined as successful clot reduction and restoration of portal venous flow at the conclusion of the procedure. Patient outcomes based on clinical presentation, adverse events, and thrombectomy-associated adverse events were recorded. RESULTS: Twenty patients, with a median age of 58 years (range, 23-72 years), underwent large-bore aspiration thrombectomy, which was technically successful in 19 of 20 (95%) patients. In 9 of 20 (45%) patients, 9 of 20 (45%) patients, and 2 of 20 (10%) patients, the 20-F, 16-F, and 24-F devices were used, respectively. Fourteen patients had a pre-existing TIPS, and 6 patients had a TIPS created. In 5 of 20 (25%) patients, overnight lysis was performed in conjunction with Inari thrombectomy. Thrombus resolution with restoration of flow was achieved in 19 of 20 (95%) cases. There were no thrombectomy-associated adverse events. The mean follow-up time was 70 days (±113) at which time primary patency of the portal venous system was present in 16 of 20 (80%) patients. CONCLUSIONS: Large-bore aspiration portal vein thrombectomy is feasible for PMVT.


Assuntos
Derivação Portossistêmica Transjugular Intra-Hepática , Trombose , Trombose Venosa , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Sucção , Estudos de Viabilidade , Resultado do Tratamento , Estudos Retrospectivos , Trombectomia/efeitos adversos , Veia Porta/cirurgia , Trombose/etiologia , Trombose Venosa/terapia
20.
J Vasc Interv Radiol ; 34(3): 466-473, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36414114

RESUMO

PURPOSE: To assess patient and provider satisfaction with interventional radiology (IR) outpatient telehealth and in-person clinic. MATERIALS AND METHODS: This institutional review board-approved study analyzed patient satisfaction with clinic via survey after an IR outpatient telehealth or in-person visit. A physician telehealth experience survey was completed by 8 IR physicians. RESULTS: During the initial survey period, 44 (83%) of 53 patients completed a survey via telephone compared with 37 (23%) of 158 patients who were offered an electronic survey during the second survey period. Of 81 respondents, 18 (22%) were in-person and 63 (78%) were via telehealth. Of the respondents, nearly all patients (97%) in the telehealth group reported satisfaction with their telehealth clinic visit, with similar rates of high patient satisfaction between in-person and telehealth visits (P = .51). Most patients (98%) in the telehealth group strongly agreed that their physician's recommendations were clear in the telehealth visit and that their visit was private, similar to in-person visits (P = .13). A telehealth visit saved time for all patients (100%), with 78% reporting >1 hour of time-saving. All IR physicians (n = 8) reported greater efficiency with telehealth clinic than with in-person clinic and that follow-up patterns would change if telehealth was available. However, all providers (100%) found telephone visits less satisfying than in-person visits, with video visits being either equally satisfying (71%) or less satisfying (29%). CONCLUSIONS: Patient satisfaction with the in-person and telehealth outpatient IR clinic was high, with patients and providers reporting time-saving and greater efficiency with telehealth, suggesting that telehealth should remain an important component of outpatient IR clinic care.


Assuntos
Radiologia Intervencionista , Telemedicina , Humanos , Satisfação do Paciente , Assistência Ambulatorial , Pacientes Ambulatoriais
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