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1.
JACC Basic Transl Sci ; 9(3): 342-360, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38559632

RESUMEN

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start. Although NET inhibitors failed in the elastase model, they prevented progression of angiotensin II-induced aneurysms with thrombus, which resembles established human disease (including thrombus development). Blockade of upstream NET mediators was more effective than interference with downstream NET molecules.

2.
Asian J Surg ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38627118

RESUMEN

OBJECTIVE: Bridging stentgrafts (BSGs) are one of the primary limiting factors regarding long-term results after fenestrated endovascular aortic repair (fEVAR). This study aims to report for the first time the outcome of a novel BSG called iCover from a national, multicentric retrospective database. METHODS: A cohort of 58 patients received 212 BSGs for the renovisceral arteries in fEVAR. Patients were followed-up clinically and with computed-tomography angiography. Study end points were mortality, occurrence of complications, technical success of the BSG implantation, defined as successful deployment with vessel patency and absence of type 1c, 3b, and 3c endoleak, and stability over the follow-up. RESULTS: Three BSG unrelated mortalities (5.1 %), four BSG unrelated major complications (6.8 %) and five minor complications (8.6 %) occurred. The technical success of iCover was 207/212 (97.6 %), target vessel patency was 100 % over a follow-up of 4.0 months, and no late BSG related endoleak was detected. In two cases, the BSG was dislodged from the balloon and could be parked in a safe position without further sequelae (0.9 %). CONCLUSION: The iCover represents a feasible BSG for fEVAR with an excellent safety profile and technical success rate in the early phase. Prudent post-dilatation and monitoring of the proximal and distal stent ends can potentially further improve outcome. Longer follow-up series are necessary.

3.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38612791

RESUMEN

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but are also recognized for their involvement in a range of pathological processes, including autoimmune diseases, cancer, and cardiovascular diseases. This review explores the intricate roles of NETs in different cardiovascular conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, and particularly in the pathogenesis of abdominal aortic aneurysms. We elucidate the mechanisms underlying NET formation and function, provide a foundational understanding of their biological significance, and highlight the contribution of NETs to inflammation, thrombosis, and tissue remodeling in vascular disease. Therapeutic strategies for preventing NET release are compared with approaches targeting components of formed NETs in cardiovascular disease. Current limitations and potential avenues for clinical translation of anti-NET treatments are discussed.


Asunto(s)
Aneurisma de la Aorta Abdominal , Sistema Cardiovascular , Trampas Extracelulares , Infarto del Miocardio , Trombosis , Humanos
5.
Mol Ther ; 32(1): 140-151, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37980543

RESUMEN

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer caused by a dominant recurrent fusion of the heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PRKACA). Current therapies such as chemotherapy and radiation have limited efficacy, and new treatment options are needed urgently. We have previously shown that FLC tumors are dependent on the fusion kinase DNAJB1::PRKACA, making the oncokinase an ideal drug target. mRNA degrading modalities such as antisense oligonucleotides or small interfering RNAs (siRNAs) provide an opportunity to specifically target the fusion junction. Here, we identify a potent and specific siRNA that inhibits DNAJB1::PRKACA expression. We found expression of the asialoglycoprotein receptor in FLC to be maintained at sufficient levels to effectively deliver siRNA conjugated to the GalNAc ligand. We observe productive uptake and siRNA activity in FLC patient-derived xenografts (PDX) models in vitro and in vivo. Knockdown of DNAJB1::PRKACA results in durable growth inhibition of FLC PDX in vivo with no detectable toxicities. Our results suggest that this approach could be a treatment option for FLC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , ARN Interferente Pequeño/genética , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , ARN Bicatenario , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP40/metabolismo , Subunidades Catalíticas de Proteína Quinasa Dependientes de AMP Cíclico/genética , Subunidades Catalíticas de Proteína Quinasa Dependientes de AMP Cíclico/metabolismo
6.
J Clin Med ; 12(24)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38137627

RESUMEN

Abdominal aortic aneurysm (AAA) and peripheral artery disease (PAD) share pathophysiological mechanisms including the activation of the fibrinolytic and innate immune system, which explains the analysis of D-dimer and myeloperoxidase (MPO) in both conditions. This study evaluates the diagnostic marker potential of both variables separately and as a combined MPO/D-dimer score for identifying patients with AAA versus healthy individuals or patients with PAD. Plasma levels of MPO and D-dimer were increased in PAD and AAA compared to healthy controls (median for MPO: 13.63 ng/mL [AAA] vs. 11.74 ng/mL [PAD] vs. 9.16 ng/mL [healthy], D-dimer: 1.27 µg/mL [AAA] vs. 0.58 µg/mL [PAD] vs. 0.38 µg/mL [healthy]). The combined MPO/D-dimer score (median 1.26 [AAA] vs. -0.19 [PAD] vs. -0.93 [healthy]) showed an improved performance in distinguishing AAA from PAD when analysed using the receiver operating characteristic curve (area under the curve) for AAA against the pooled data of healthy controls + PAD: 0.728 [MPO], 0.749 [D-dimer], 0.801 [score]. Diagnostic sensitivity and specificity ranged at 82.9% and 70.2% (for score cut-off = 0). These findings were confirmed for a separate collective of AAA patients with 35% simultaneous PAD. Thus, evaluating MPO together with D-dimer in a simple score may be useful for diagnostic detection and the distinction of AAA from athero-occlusive diseases like PAD.

7.
Strahlenther Onkol ; 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37676483

RESUMEN

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

8.
Biomedicines ; 11(8)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37626780

RESUMEN

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.

9.
Front Cardiovasc Med ; 10: 1219744, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37576114

RESUMEN

Objective: This retrospective study evaluates the performance of UK National Institute for Health and Care Excellence (NICE) Guidelines on management of ruptured abdominal aortic aneurysms in a "real world setting" by emulating a hypothetical target trial with data from two European Aortic Centers. Methods: Clinical data was retrospectively collected for all patients who had undergone ruptured endovascular aneurysm repair (rEVAR) and ruptured open surgical repair (rOSR). Survival analysis was performed comparing NICE compliance to usual care strategy. NICE compliers were defined as: female patients undergoing rEVAR; male patients >70 years old undergoing rEVAR; and male patients ≤70 years old undergoing rOSR. Hemodynamic instability was considered additionally. Results: This multicenter study included 298 patients treated for rAAA. The majority of patients were treated with rOSR (186 rOSR vs. 112 rEVAR). Overall, 184 deaths (68 [37%] with rEVAR and 116 [63%] with rOSR) were observed during the study period. Overall survival under usual care was 69.2% at 30 days, 56.5% at one year, and 42.4% at 5 years. NICE compliance gave survival outcomes of 73.1% at 30 days, 60.2% at 1 year and 42.9% at 5 years. The risk ratios at these time points, comparing NICE-compliance to usual care, were 0.88, 0.92 and 0.99, respectively. Conclusions: We support NICE recommendations to manage men below the age of 71 years and hemodynamic stability with rOSR. There was a slight survival advantage for NICE compliers overall, in men >70 years and women of all ages.

10.
Circ Res ; 133(7): 542-558, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37646165

RESUMEN

BACKGROUND: Using proteomics, we aimed to reveal molecular types of human atherosclerotic lesions and study their associations with histology, imaging, and cardiovascular outcomes. METHODS: Two hundred nineteen carotid endarterectomy samples were procured from 120 patients. A sequential protein extraction protocol was employed in conjunction with multiplexed, discovery proteomics. To focus on extracellular proteins, parallel reaction monitoring was employed for targeted proteomics. Proteomic signatures were integrated with bulk, single-cell, and spatial RNA-sequencing data, and validated in 200 patients from the Athero-Express Biobank study. RESULTS: This extensive proteomics analysis identified plaque inflammation and calcification signatures, which were inversely correlated and validated using targeted proteomics. The inflammation signature was characterized by the presence of neutrophil-derived proteins, such as S100A8/9 (calprotectin) and myeloperoxidase, whereas the calcification signature included fetuin-A, osteopontin, and gamma-carboxylated proteins. The proteomics data also revealed sex differences in atherosclerosis, with large-aggregating proteoglycans versican and aggrecan being more abundant in females and exhibiting an inverse correlation with estradiol levels. The integration of RNA-sequencing data attributed the inflammation signature predominantly to neutrophils and macrophages, and the calcification and sex signatures to smooth muscle cells, except for certain plasma proteins that were not expressed but retained in plaques, such as fetuin-A. Dimensionality reduction and machine learning techniques were applied to identify 4 distinct plaque phenotypes based on proteomics data. A protein signature of 4 key proteins (calponin, protein C, serpin H1, and versican) predicted future cardiovascular mortality with an area under the curve of 75% and 67.5% in the discovery and validation cohort, respectively, surpassing the prognostic performance of imaging and histology. CONCLUSIONS: Plaque proteomics redefined clinically relevant patient groups with distinct outcomes, identifying subgroups of male and female patients with elevated risk of future cardiovascular events.


Asunto(s)
Aterosclerosis , Calcinosis , Femenino , Humanos , Masculino , Proteómica , Caracteres Sexuales , Versicanos , alfa-2-Glicoproteína-HS
11.
Int J Surg ; 109(8): 2249-2257, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37402309

RESUMEN

BACKGROUND: Monitoring of abdominal aortic aneurysms (AAAs) is currently based on serial measurements of maximum aortic diameter. Additional assessment of aneurysm volume has previously been proposed to possibly improve growth prediction and treatment decisions. To evaluate the use of supplementing volume measurements, the authors aimed to characterise the growth distribution of AAA volume and to compare the growth rates of the maximum diameter and volume at the patient level. METHODS: Maximum diameter and volume were monitored every 6 months in 84 patients with small AAAs, with a total of 331 computed tomographic angiographies (with initial maximum diameters of 30-68 mm). A previously developed statistical growth model for AAAs was applied to assess the growth distribution of volume and to compare individual growth rates for volume and for maximum diameter. RESULTS: The median (25-75% quantile) expansion in volume was 13.4 (6.5-24.7) % per year. Cube root transformed volume and maximum diameter showed a closely linear association with a within-subject correlation of 0.77. At the surgery threshold maximum diameter of 55 mm, the median (25-75% quantile) volume was 132 (103-167) ml. In 39% of subjects, growth rates for volume and maximum diameter were equivalent, in 33% growth was faster in volume and in 27% growth was faster in maximum diameter. CONCLUSION: At the population level, volume and maximum diameter show a substantial association such that the average volume is approximately proportional to the average maximum diameter raised to a power of three. At the individual level, however, in the majority of patient's AAAs grow at different pace in different dimensions. Hence, closer monitoring of aneurysms with sub-critical diameter but suspicious morphology may benefit from complementing maximum diameter by volume or related measurements.


Asunto(s)
Aneurisma de la Aorta Abdominal , Humanos , Estudios de Cohortes , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Factores de Riesgo
12.
Cells ; 12(14)2023 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-37508529

RESUMEN

Toll-like receptors (TLRs) have a critical role in the pathogenesis and disease course of viral infections. The induced pro-inflammatory responses result in the disturbance of the endovascular surface layer and impair vascular homeostasis. The injury of the vessel wall further promotes pro-thrombotic and pro-coagulatory processes, eventually leading to micro-vessel plugging and tissue necrosis. Moreover, TLRs have a direct role in the sensing of viruses and platelet activation. TLR-mediated upregulation of von Willebrand factor release and neutrophil, as well as macrophage extra-cellular trap formation, further contribute to (micro-) thrombotic processes during inflammation. The following review focuses on TLR signaling pathways of TLRs expressed in humans provoking pro-thrombotic responses, which determine patient outcome during viral infections, especially in those with cardiovascular diseases.


Asunto(s)
Trombosis , Virosis , Humanos , Receptores Toll-Like , Transducción de Señal , Inflamación
13.
J Vasc Surg ; 78(6): 1383-1391.e5, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37330151

RESUMEN

OBJECTIVE: To assess the early experience with modified version of simplified bare-wire target vessel (SMART) technique, implying delivery of bridging stent grafts without historically established sheath support, and to compare its outcome to standard endovascular aortic repair procedures with fenestrated/branched devices. METHODS: A retrospective analysis of 102 consecutive patients treated with fenestrated/branched devices from January 2020 to December 2022 was undertaken. The study population was divided into three groups-a sheath group (SG), SMART group, and nonsheath group (NSG). Primary end points were radiation exposure (dose-area product), fluoroscopy time, dose of contrast agent, operation time, and incidence of intraoperative target vessel (TV) complications and additional procedures. Freedom from secondary TV related reinterventions at the three follow-up phases were defined as secondary end points. RESULTS: A total of 183 TVs (38.8% visceral arteries [VA]; 56.3% renal arteries [RA]) in the SG, 36 TVs (44.4% VA, 55.6% RA) in the SMART group, and 168 TVs (47.6% VA; 50% RA) in the NSG were accessed. The mean number of fenestrations and bridging stent grafts was equally distributed in all three groups. The SMART group only included cases treated with fenestrated devices. The dose-area product was significantly lower in the SMART (median, 203 Gy × cm2; interquartile range [IQR], 179-365 Gy × cm2) and NSG (median, 340 Gy × cm2; IQR, 220-651 Gy × cm2) groups vs the SG (median, 464 Gy × cm2; IQR, 267-871 Gy × cm2; P = .007). Operation time was also significantly lower in the NSG (median, 265 minutes; IQR, 221-337 minutes) and SMART (median, 292 minutes; IQR, 234-351 minutes) groups vs the SG (median, 326 minutes; IQR, 277-375 minutes; P = .004), respectively. Intraoperative TV-related complications were most frequently observed in the SG (9/183 TVs; P = .008). CONCLUSIONS: This study reports the outcomes of three currently available TV stenting approaches. Previously reported SMART technique, and its modified version (NSG) proved to be a safe alternative to historically established TV stenting technique with sheath support (SG).


Asunto(s)
Reparación Endovascular de Aneurismas , Stents , Humanos , Estudios Retrospectivos , Medios de Contraste , Fluoroscopía , Complicaciones Intraoperatorias
14.
Free Radic Biol Med ; 206: 94-105, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37353175

RESUMEN

There is accumulating evidence that pro-inflammatory features are inherent to mitochondrial DNA and oxidized DNA species. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most frequently studied oxidatively generated lesion. Modified DNA reaches the circulation upon cell apoptosis, necrosis or neutrophil extracellular trap (NET) formation. Standard chromatography-based techniques for the assessment of 8-oxodGuo imply degradation of DNA to a single base level, thus precluding the attribution to a nuclear or mitochondrial origin. We therefore aimed to establish a protocol for the concomitant assessment of oxidized mitochondrial and nuclear DNA from human plasma samples. We applied immunoprecipitation (IP) for 8-oxodGuo to separate oxidized from non-oxidized DNA species and subsequent quantitative polymerase chain reaction (qPCR) to assign them to their subcellular source. The IP procedure failed when applied directly to plasma samples, i.e. isotype control precipitated similar amounts of DNA as the specific 8-oxodGuo antibody. In contrast, DNA isolation from plasma prior to the IP process provided assay specificity with little impact on DNA oxidation status. We further optimized sensitivity and efficiency of qPCR analysis by reducing amplicon length and targeting repetitive nuclear DNA elements. When the established protocol was applied to plasma samples of abdominal aortic aneurysm (AAA) patients and control subjects, the AAA cohort displayed significantly elevated circulating non-oxidized and total nuclear DNA and a trend for increased levels of oxidized mitochondrial DNA. An enrichment of mitochondrial versus nuclear DNA within the oxidized DNA fraction was seen for AAA patients. Regarding the potential source of circulating DNA, we observed a significant correlation of markers of neutrophil activation and NET formation with nuclear DNA, independent of oxidation status. Thus, the established method provides a tool to detect and distinguish the release of oxidized nuclear and mitochondrial DNA in human plasma and offers a refined biomarker to monitor disease conditions of pro-inflammatory cell and tissue destruction.


Asunto(s)
Aneurisma de la Aorta Abdominal , Desoxiguanosina , Humanos , 8-Hidroxi-2'-Desoxicoguanosina , ADN Mitocondrial/genética , Oxidación-Reducción , Aneurisma de la Aorta Abdominal/genética
15.
Biomedicines ; 11(5)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37238988

RESUMEN

Complex endovascular aortic repair (coEVAR) of thoracoabdominal aortic aneurysms (TAAA) has greatly evolved in the past decades. Despite substantial improvements of postoperative care, spinal cord injury (SCI) remains the most devastating complication of coEVAR being associated with impaired patient outcome and having an impact on long-term survival. The rising number of challenges of coEVAR, essentially associated with an extensive coverage of critical blood vessels supplying the spinal cord, resulted in the implementation of dedicated SCI prevention protocols. In addition to maintenance of adequate spinal cord perfusion pressure (SCPP), early detection of SCI plays an integral role in intra- and postoperative patient care. However, this is challenging due to difficulties with clinical neurological examinations during patient sedation in the postoperative setting. There is a rising amount of evidence, suggesting that subclinical forms of SCI might be accompanied by an elevation of biochemical markers, specific to neuronal tissue damage. Addressing this hypothesis, several studies have attempted to assess the potential of selected biomarkers with regard to early SCI diagnosis. In this review, we discuss biomarkers measured in patients undergoing coEVAR. Once validated in future prospective clinical studies, biomarkers of neuronal tissue damage may potentially add to the armamentarium of modalities for early SCI diagnosis and risk stratification.

16.
Int J Mol Sci ; 24(10)2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37240352

RESUMEN

Interleukin (IL-33) and the ST2 receptor are implicated in the pathogenesis of atherosclerosis. Soluble ST2 (sST2), which negatively regulates IL-33 signaling, is an established biomarker in coronary artery disease and heart failure. Here we aimed to investigate the association of sST2 with carotid atherosclerotic plaque morphology, symptom presentation, and the prognostic value of sST2 in patients undergoing carotid endarterectomy. A total of 170 consecutive patients with high-grade asymptomatic or symptomatic carotid artery stenosis undergoing carotid endarterectomy were included in the study. The patients were followed up for 10 years, and the primary endpoint was defined as a composite of adverse cardiovascular events and cardiovascular mortality, with all-cause mortality as the secondary endpoint. The baseline sST2 showed no association with carotid plaque morphology assessed using carotid duplex ultrasound (B 0.051, 95% CI -0.145-0.248, p = 0.609), nor with modified histological AHA classification based on morphological description following surgery (B -0.032, 95% CI -0.194-0.130, p = 0.698). Furthermore, sST2 was not associated with baseline clinical symptoms (B -0.105, 95% CI -0.432-0.214, p = 0.517). On the other hand, sST2 was an independent predictor for long-term adverse cardiovascular events after adjustment for age, sex, and coronary artery disease (HR 1.4, 95% CI 1.0-2.4, p = 0.048), but not for all-cause mortality (HR 1.2, 95% CI 0.8-1.7, p = 0.301). Patients with high baseline sST2 levels had a significantly higher adverse cardiovascular event rate as compared to patients with lower sST2 (log-rank p < 0.001). Although IL-33 and ST2 play a role in the pathogenesis of atherosclerosis, sST2 is not associated with carotid plaque morphology. However, sST2 is an excellent prognostic marker for long-term adverse cardiovascular outcomes in patients with high-grade carotid artery stenosis.


Asunto(s)
Aterosclerosis , Estenosis Carotídea , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico , Interleucina-33 , Proteína 1 Similar al Receptor de Interleucina-1 , Aterosclerosis/complicaciones , Biomarcadores
17.
Explor Target Antitumor Ther ; 4(2): 355-365, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37205313

RESUMEN

Aim: Coagulation is frequently activated in cancer patients and has been correlated with an unfavorable prognosis. To evaluate whether a putative release of tissue factor (TF) by circulating tumor cells (CTCs) represents a target to impair the dissemination of small cell lung cancer (SCLC), the expression of relevant proteins in a panel of permanent SCLC and SCLC CTC cell lines that have been established at the Medical University of Vienna. Methods: Five CTC and SCLC lines were analyzed using a TF enzyme-linked immunosorbent assay (ELISA) tests, RNA sequencing, and western blot arrays covering 55 angiogenic mediators. Furthermore, the influence of topotecan and epirubicin as well as hypoxia-like conditions on the expression of these mediators was investigated. Results: The results demonstrate that the SCLC CTC cell lines express no significant amounts of active TF but thrombospondin-1 (TSP-1), urokinase-type plasminogen activator receptor (uPAR), vascular endothelial-derived growth factor (VEGF) and angiopoietin-2 in two cases. The major difference between the SCLC and SCLC CTC cell lines found was the loss of the expression of angiogenin in the blood-derived CTC lines. Topotecan and epirubicin decreased the expression of VEGF, whereas hypoxia-like conditions upregulated VEGF. Conclusions: Active TF capable of triggering coagulation seems not to be expressed in SCLC CTC cell lines in significant levels and, thus, CTC-derived TF seems dispensable for dissemination. Nevertheless, all CTC lines form large spheroids, termed tumorospheres, which may become trapped in clots of the microvasculature and extravasate in this supportive microenvironment. The contribution of clotting to the protection and dissemination of CTCs in SCLC may be different from other solid tumors such as breast cancer.

18.
Int J Surg ; 109(4): 861-869, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36999821

RESUMEN

BACKGROUND: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease associated with high morbidity and mortality. Currently, surgical intervention is the only treatment option, and there is no drug therapy available for AAA. Hence, surveillance of AAA until indication for surgery may impact patient quality of life (QoL). There is a paucity of high-quality observational data on health status and QoL, particularly among AAA patients participating in randomized controlled trials. The objective of this study was to compare the QoL scores of AAA patients on surveillance to those of AAA patients enrolled in the MetAAA trial. MATERIAL AND METHODS: Overall, 54 MetAAA trial patients and 23 AAA patients under regular surveillance for small AAA (part of a longitudinal monitoring study) were asked to complete three established and validated (in total 561 longitudinally collected) QoL questionnaires: the 36-Item Short Form Health Survey (SF-36), the Aneurysm Symptom Rating Questionnaire (ASRQ), and the Aneurysm-Dependent Quality of Life questionnaire (ADQoL). RESULTS: A superior health status and QoL was found in AAA patients participating in the MetAAA trial compared to AAA patients under regular surveillance. In detail, MetAAA trial patients showed superior general health perception ( P =0.012), higher energy level ( P =0.036) as well as enhanced emotional well-being ( P =0.044) and fewer limitations due to general malaise ( P =0.021), which was subsequently reflected in an overall superior current QoL score ( P =0.039) compared to AAA patients under regular surveillance. CONCLUSION: AAA patients enrolled in the MetAAA trial showed superior health status and QoL compared to AAA patients under regular surveillance.


Asunto(s)
Aneurisma de la Aorta Abdominal , Calidad de Vida , Humanos , Estudios Retrospectivos , Aneurisma de la Aorta Abdominal/cirugía , Encuestas y Cuestionarios
19.
J Vasc Surg ; 77(5): 1359-1366.e2, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36587811

RESUMEN

OBJECTIVE: Endovascular aortic repair (EVAR) with fenestrated (F-EVAR) or branched (B-EVAR) endografts represents an indispensable tool of modern patient care in vascular surgery. The purpose of this retrospective study was to evaluate the center's initial experience of F/B-EVAR procedures performed under biplane angiography guidance compared with a historical control group. METHODS: From January 2020 to March 2022, 80 consecutive patients underwent F/B-EVAR under general anesthesia at a single institution. As from January 2021, the deployment of complex stent grafts was performed using an alternative intraoperative imaging modality-a biplane fluoroscopy and angiography. The cohort was divided into monoplane (MPA) and biplane (BPA) groups according to the imaging modality applied. The end points were operation time, fluoroscopy time, radiation exposure, dose of contrast agent, and technical success. RESULTS: The MPA group included 59 patients (78% male; median age; 74 years; interquartile range [IQR], 66-78 years) and the BPA group 21 patients (85.7% males; median age, 75 years; IQR, 69-79 years). Operation time (median, 320 minutes; IQR, 266-376 minutes) versus (median, 275 minutes; IQR, 216-333 minutes) was significantly lower in the BPA group (P = .006). The median fluoroscopy time (median, 82 minutes; IQR, 57-110 minutes vs median, 68 minutes; IQR, 54-92 minutes), contrast agent volume applied (median, 220 mL; IQR, 179-250 mL vs median, 200 mL; IQR, 170-250 mL), and radiation dose (dose-area product, median, 413 Gy × cm2; IQR, 249-736 Gy × cm2; vs median, 542 Gy × cm2; IQR, 196-789 Gy × cm2) were similar in both groups. Technical success of 96.6% (57/59 cases) versus 100% (21/21 cases) could be achieved in MPA and BPA group, respectively. CONCLUSIONS: F/B-EVAR procedures performed under BPA guidance were associated with a significant decrease in operation time.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Masculino , Anciano , Femenino , Medios de Contraste , Prótesis Vascular , Reparación Endovascular de Aneurismas , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/métodos , Estudios Retrospectivos , Aortografía/efectos adversos , Aortografía/métodos , Resultado del Tratamiento , Dosis de Radiación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Fluoroscopía , Aneurisma de la Aorta Abdominal/cirugía
20.
J Endovasc Ther ; : 15266028221149919, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36680393

RESUMEN

PURPOSE: In penetrating aortic ulcers (PAUs), limited data support tubular thoracic endovascular aortic repair (TEVAR) as a viable treatment option. For treatment of more proximal PAUs, hybrid approaches and-more recently-scalloped TEVAR (scTEVAR) have been advocated. Outcomes of scTEVAR specifically for PAUs have not yet been reported. This study reports long-term outcomes for tubular and scTEVAR in PAUs and compares the safety profile in both cohorts regarding the significantly more proximal landing zone (LZ) for scTEVAR. MATERIALS AND METHODS: This single-center retrospective cohort study includes all nonacute patients treated for complicated PAU with scTEVAR and tubular TEVAR. Patient and PAU characteristics as well as procedural success, complication and reintervention rates, and all-cause and aortic mortality were analyzed. RESULTS: Of 212 TEVAR procedures reviewed, 21 patients with tubular TEVAR and 19 patients with scTEVAR were included. Patient and PAU characteristics were similar, and LZ was significantly more proximal in the scTEVAR cohort (p=0.0001), with similar number and types of supra-aortic revascularization procedures. Clinical success was reached in all 40 patients (100%), and reintervention rate was 2/21 (9.5%) and 1/19 (5.3%), respectively. Over the mean follow-up of 63 (TEVAR) and 53 (scTEVAR) months, clinical success was stable in all patients with one (abdominal) aortic-related mortality in the scTEVAR cohort. CONCLUSION: Treatment of complicated PAUs with TEVAR as well as scTEVAR provides excellent and similar clinical success, stability of clinical success, and aortic survival with acceptable complication and reintervention rates. Scalloped TEVAR safely lengthens the proximal sealing zone to address more proximal pathologies. CLINICAL IMPACT: Treatment of asymptomatic complicated penetrating aortic ulcers (PAUs) with thoracic endovascular aortic repair (TEVAR) provides excellent clinical success and acceptable complication and reintervention rates. More patients become amenable to endovascular treatment by including scalloped TEVAR (scTEVAR) as a means to safely lengthen the proximal sealing zone to address more proximal pathologies.

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