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1.
Asian J Surg ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38627118

RESUMO

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.

2.
J Vasc Surg ; 78(6): 1383-1391.e5, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37330151

RESUMO

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).


Assuntos
Correção Endovascular de Aneurisma , Stents , Humanos , Estudos Retrospectivos , Meios de Contraste , Fluoroscopia , Complicações Intraoperatórias
3.
Eur J Cardiothorac Surg ; 63(5)2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36916747

RESUMO

OBJECTIVES: Endovascular treatment has been suggested as an alternative for open surgery for type A aortic dissection, but current devices have severe anatomical limitations. This study assesses the computed tomography-based anatomical suitability of currently manufactured stent grafts as well as 2 embodiments of valve-carrying devices. METHODS: In a retrospective single-centre cohort of 200 consecutive ascending/arch operations between 2009 and 2018, a total of 112 patients with type A aortic dissections were identified and evaluated for endovascular candidacy based on the locations of the entries, the landing zone diameters/lengths and the supra-aortic vessel origins according to the anatomical instructions for use criteria of 6 commercially available (tubular, branched or fenestrated) stent grafts. Two suggested valve-carrying devices with inner branches or fenestrations for the coronary arteries and branches for the supra-aortic vessels were also evaluated. RESULTS: The anatomical feasibility for commercial stent grafts ranged from 4% to 21%. The main limitations were proximal landing zone diameter (considering oversizing <15%), length due to dilatation and an entry too close to the sinotubular junction. For the valve-carrying conduits, anatomical feasibility was between 31% and 80%, with the main limiting factors being the diameter of the aortic annulus and its distance to the coronary arteries. CONCLUSIONS: The anatomical applicability of currently manufactured stent grafts for the treatment of type A aortic dissection is limited mainly by the absence of a suitable proximal landing zone in the ascending aorta and might substantially be improved by anchoring in the aortic annulus using a valve-carrying device that uses either fenestrations or branches for the coronary arteries.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Prótese Vascular , Implante de Prótese Vascular/métodos , Aneurisma da Aorta Torácica/cirurgia , Stents , Estudos Retrospectivos , Procedimentos Endovasculares/métodos , Desenho de Prótese , Resultado do Tratamento
4.
J Vasc Surg ; 77(5): 1359-1366.e2, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36587811

RESUMO

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.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Masculino , Idoso , Feminino , Meios de Contraste , Prótese Vascular , Correção Endovascular de Aneurisma , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Estudos Retrospectivos , Aortografia/efeitos adversos , Aortografia/métodos , Resultado do Tratamento , Doses de Radiação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fluoroscopia , Aneurisma da Aorta Abdominal/cirurgia
5.
J Endovasc Ther ; : 15266028221149919, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36680393

RESUMO

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.

6.
Discov Oncol ; 13(1): 84, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048281

RESUMO

KRAS is mutated in approximately 25% of cancer patients and first KRAS G12C-specific inhibitors showed promising responses. Pancreatic cancer has the highest frequency of KRAS mutations but the prevailing KRAS G12D mutation is difficult to target. Inhibition of the GTP exchange factor (GEF) SOS1-KRAS interaction impairs oncogenic signaling independently of the specific KRAS mutations. In general, cell lines exhibiting KRAS mutations show specific alterations in respect to glucose utilization, signal transduction and stress survival. The aim of this investigation was to check the putative synergy of the SOS1 inhibitor BAY-293 with modulators targeting specific vulnerabilities of KRAS-mutated cell lines in vitro. The cytotoxicity of BAY-293 combinations was tested against MIA PaCa-2 (G12C), AsPC1 (G12D) and BxPC3 (KRAS wildtype) cell lines using MTT tests and calculation of the combination indices (CI) according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose utilization, inhibitors of the downstream MAPK pathway and several chemotherapeutics in dependence of the specific KRAS status of the cell lines. In particular, divergent responses for BAY-293 combinations between pancreatic and NSCLC cell lines were observed for linsitinib, superior inhibitory effects of trametinib and PD98059 in NSCLC, and lack of activity with doxorubicin in case of the pancreatic cell lines. Phosphoproteome analysis revealed inhibition of distinct signaling pathways by BAY-293 for MIA PaCa-2 on the one hand and for Aspc1 and BH1362 on the other hand. In conclusion, BAY-293 exhibits synergy with drugs in dependence of the tumor type and specific KRAS mutation.

7.
J Vasc Surg ; 76(6): 1440-1448, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36028159

RESUMO

OBJECTIVE: Endovascular repair of post-type A aortic dissection (PTAD) after open ascending replacement has recently been shown as safe and feasible, but with limited anatomic applicability because only one stent graft was evaluated. We assessed anatomic and clinical applicability of six commercially available branched/fenestrated stent grafts for endovascular repair of PTAD. METHODS: On postoperative CT scans of 101 patients, we measured the aortic diameter at the sinutubular junction, supra-aortic vessels, and descending aorta, as well as the distances between these landmarks along the outer curvature of the arch and the diameters of the supra-aortic vessel. Anatomic applicability was evaluated according to the instructions for use, clinical applicability with regard to supra-aortic and iliac arteries. Assessed devices were the Cook aortic double branch, Terumo double branch, Najuta fenestrated, Endospan Nexus, Medtronic Mona LSA, and Gore TAG thoracic branch. RESULTS: Single devices were anatomically and clinically applicable between 19 of 101 (Mona LSA) and 83 of 101 (Najuta) cases. Reasons for rejection varied considerably across devices. With all devices available, anatomic applicability was 97 of 101 and clinical applicability 95 of 101. Combinations of a fenestrated and a branched device showed the most favorable clinical applicability for a pair of two devices, ranging from 86 of 101 to 94 of 101. CONCLUSIONS: Anatomic and clinical applicability of endovascular devices for the repair of PTAD is high for fenestrated and branched devices, and very high for the combination of fenestrated and branched devices. Manufacturers should amend specific device requirements for PTAD. Surgeons should emphasize the need for a sufficiently long and straight graft as a potential landing zone.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Procedimentos Endovasculares/efeitos adversos , Desenho de Prótese , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Stents/efeitos adversos
8.
Radiologie (Heidelb) ; 62(7): 592-600, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-35736998

RESUMO

All patients who underwent endovascular aortic repair (EVAR) need a thorough follow-up, at least yearly. Contrast-enhanced ultrasound and computed tomography angiography (CTA) are the most important modalities for detection of endoleaks, whereby CTA allows better differentiation of endoleak type. High pressure endoleaks (type I and III) are an absolute indication for treatment if they do not resolve spontaneously in the short term. Type II endoleaks are mostly benign and may be routinely controlled if there is no progression of the aneurysm. Type II endoleaks associated with aneurysm progression may be treated with embolization; however, whether they must be treated is a matter of discussion. Nonetheless, a type II endoleak must be treated when progression shortens the aneurysm neck and the threat of a type I endoleak is at hand. Type I endoleaks are the main limitation of stent grafts. An adequate proximal landing zone is the best prevention for type I endoleaks, even if fenestrated stent grafts have to be used. Various fixation devices for short necks are currently under investigation.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Endoleak/diagnóstico , Procedimentos Endovasculares/efeitos adversos , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Radiologie (Heidelb) ; 62(7): 586-591, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-35726073

RESUMO

BACKGROUND: Today, complex abdominal aortic pathologies involving the visceral arteries and without an adequate proximal neck can be treated using fenestrated/branched endovascular aortic repair (FEVAR/BEVAR) with similar safety and success rates as infrarenal aortic pathologies treated with tubular EVAR. METHODICAL INNOVATIONS AND CHALLENGES: Fenestrations (if the vessel originates from a nondilated aorta) or branches (if the vessel originates from a dilated aorta) may be used for the visceral arteries. Both types of openings are sealed via bridging stent grafts that connect to the target vessel. Multiple manufacturers offer fenestrated or branched endoprostheses, with only a few being CE certified and the majority in Europe being patient-specific custom-made devices. Therefore, they require a certain delivery time which precludes acute patients from such treatment. However, two stent grafts with four branches for thoracoabdominal aneurysms are available off the shelf and are anatomically suitable for the majority of patients, thus, allowing for acute treatment. All FEVAR and BEVAR main bodies require bridging stent grafts, all of which are used off-label. RECOMMENDATIONS: As bridging stent grafts are one of the main reasons for reinterventions, one should be aware of fractures and kinking of the bridging stent grafts during follow-up and should refrain from using single-layered bridging stent grafts in BEVAR.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aorta , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Humanos , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Resultado do Tratamento
10.
J Thorac Cardiovasc Surg ; 164(5): 1379-1389.e1, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35534283

RESUMO

OBJECTIVE: For thoracic endovascular aortic repair of the arch, branched and fenestrated endografts are available with different limitations regarding anatomy and extent of the pathology. Comparisons are lacking in the literature. The aim of this study was to compare the results of 2 currently commercially available devices for branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair. METHODS: In a retrospective, multicenter cohort study, a consecutive patient series treated with branched thoracic endovascular aortic repair or fenestrated thoracic endovascular aortic repair for aortic arch pathologies was assessed. Baseline characteristics, procedural fenestrated thoracic endovascular aortic repair, and outcome were analyzed. Furthermore, the potential anatomic feasibility of the respective alternate device was assessed on the preoperative computed tomography scans. RESULTS: The branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair cohorts consisted of 20 and 34 patients, respectively, with similar comorbidities; indication was aneurysm in 65% and 79%, penetrating aortic ulcer in 20% and 9%, and dissection in the remaining procedures, respectively. Technical success was achieved in all but 1 patient. Perioperative mortality and major stroke rate were both 10% in branched thoracic endovascular aortic repair and 0% and 3% in fenestrated thoracic endovascular aortic repair, respectively. During follow-up of 31 and 40 months, 1 branch occlusion occurred in the branched thoracic endovascular aortic repair cohort, and 2 late endoleaks occurred in the fenestrated thoracic endovascular aortic repair group. One aortic death occurred. Although 35% of patients undergoing branched thoracic endovascular aortic repair were anatomically suitable for fenestrated thoracic endovascular aortic repair, 91% of those undergoing fenestrated thoracic endovascular aortic repair were suitable for branched thoracic endovascular aortic repair. CONCLUSIONS: Both branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair show excellent technical success and acceptable complication rates, whereas branched thoracic endovascular aortic repair tends toward higher morbidity, especially stroke rates. By offering fenestrated thoracic endovascular aortic repair along with branched thoracic endovascular aortic repair, aortic centers could potentially lower complication rates and simultaneously still treat a wide range of anatomies.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular/efeitos adversos , Estudos de Coortes , Humanos , Complicações Pós-Operatórias , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
11.
Cardiovasc Intervent Radiol ; 45(6): 744-751, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35391546

RESUMO

PURPOSE: To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA). METHODS: In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded. RESULTS: Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176). CONCLUSION: Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose. LEVEL OF EVIDENCE: 2b, retrospective cohort study.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Humanos , Desenho de Prótese , Estudos Retrospectivos , Stents , Resultado do Tratamento , Extremidade Superior/irrigação sanguínea
12.
Insights Imaging ; 13(1): 62, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35347467

RESUMO

OBJECTIVE: To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA). METHODS: From a multicenter bEVAR complication database, structural BSG failures were identified. Patient and BSG characteristics, detection mode, failure type, treatment and outcome were recorded and compared with bEVAR patients with intact BSGs. RESULTS: Twenty-three BSG failures were detected in 12 patients with only 43% directly identified in CTA, after a mean of 21.4 months after implantation. The BSGs were Advanta (n = 4), E-Ventus (n = 16) and BeGraft (n = 3) in 10 renal, 9 superior mesenteric, and 4 celiac branches. Religning with another BSG was successful in 20/22 cases, one BSG failure necessitated renal branch embolization (organ loss), and one mesenteric bypass surgery. Two reintervention-related mortalities occurred. CONCLUSION: Structural failure of BSGs is a serious limitation for bEVAR, which can result in high reintervention rates and serious complications. BSG failure typically occurs in single-layer types and events are clustered in patients. The necessary reinterventions carry serious morbidity and mortality. Since the use as BSG in bEVAR is off-label with all current BSG manufacturers, caution is advised regarding patient-informed consent.

13.
Invest New Drugs ; 40(2): 215-223, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34596822

RESUMO

In the absence of suitable molecular markers, non-small cell lung cancer (NSCLC) patients have to be treated with chemotherapy with poor results at advanced stages. Therefore, the activity of the anticancer marine drug fascaplysin was tested against primary NSCLC cell lines established from pleural effusions. Cytotoxicity of the drug or combinations were determined using MTT assays and changes in intracellular phosphorylation by Western blot arrays. Fascaplysin revealed high cytotoxicity against NSCLC cells and exhibit an activity pattern different of the standard drug cisplatin. Furthermore, fascaplysin synergizes with the EGFR tyrosine kinase inhibitor (TKI) afatinib to yield a twofold increased antitumor effect. Interaction with the Chk1/2 inhibitor AZD7762 confirm the differential effects of fascplysin and cisplatin. Protein phosphorylation assays showed hypophosphorylation of Akt1/2/3 and ERK1/2 as well as hyperphosphorylation of stress response mediators of H1299 NSCLC cells. In conclusion, fascaplysin shows high cytotoxicity against pleural primary NSCLC lines that could be further boosted when combined with the EGFR TKI afatinib.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Afatinib/farmacologia , Afatinib/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/uso terapêutico , Quinase 4 Dependente de Ciclina/uso terapêutico , Receptores ErbB , Humanos , Indóis , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
14.
Br J Surg ; 109(2): 211-219, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34849588

RESUMO

BACKGROUND: The most relevant determinant in scheduling monitoring intervals for abdominal aortic aneurysms (AAAs) is maximum diameter. The aim of the study was to develop a statistical model that takes into account specific characteristics of AAA growth distributions such as between-patient variability as well as within-patient variability across time, and allows probabilistic statements to be made regarding expected AAA growth. METHODS: CT angiography (CTA) data from patients monitored at 6-month intervals with maximum AAA diameters at baseline between 30 and 66 mm were used to develop the model. By extending the model of geometric Brownian motion with a log-normal random effect, a stochastic growth model was developed. An additional set of ultrasound-based growth data was used for external validation. RESULTS: The study data included 363 CTAs from 87 patients, and the external validation set comprised 390 patients. Internal and external cross-validation showed that the stochastic growth model allowed accurate description of the distribution of aneurysm growth. Median relative growth within 1 year was 4.1 (5-95 per cent quantile 0.5-13.3) per cent. Model calculations further resulted in relative 1-year growth of 7.0 (1.0-16.4) per cent for patients with previously observed rapid 1-year growth of 10 per cent, and 2.6 (0.3-8.3) per cent for those with previously observed slow growth of 1 per cent. The probability of exceeding a threshold of 55 mm was calculated to be 1.78 per cent at most when adhering to the current RESCAN guidelines for rescreening intervals. An online calculator based on the fitted model was made available. CONCLUSION: The stochastic growth model was found to provide a reliable tool for predicting AAA growth.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/patologia , Modelos Estatísticos , Idoso , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Humanos , Masculino , Prognóstico , Fatores de Risco , Processos Estocásticos , Fatores de Tempo
15.
Transl Oncol ; 14(12): 101230, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34598083

RESUMO

KRAS is mutated in approximately 25% of Non-small Cell Lung Cancer (NSCLC) patients and first specific inhibitors showed promising responses that may be improved by concurrent interference with downstream signaling pathways. Cell lines exhibiting KRAS mutations show specific sensitivities to modulators affecting glucose utilization, signal transduction and cell survival. Novel SOS1-directed inhibitors with a broader anticancer coverage such as BAY-293 and BI-3406 inhibit KRAS through the hindrance of SOS1-KRAS interactions. The aim of this study was to check the putative synergy of BAY-293 with modulators having revealed specific vulnerabilities of KRAS-mutated cell lines. The present investigation tested the cytotoxicity of BAY-293 combinations against a series of Osimertinib-resistant primary NSCLC cell lines using MTT tests and calculation of combination indices according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose metabolism, inhibitors of cellular proliferation, several chemotherapeutics and a range of diverse modulators, thus corroborating the chemosensitivities of cells expressing mutated KRAS. In conclusion, BAY-293 exerts cytotoxicity with a wide range of drugs against Osimertinib-resistant primary NSCLC cell lines. The administration of pan-KRAS inhibitors alone may be limited in vivo by toxicity to normal tissues but made feasible by its use as part of suitable drug combinations. This study shows that BAY-293 combinations are active against NSCLC cells not further amenable to mutated EGFR-directed targeted therapy and results likewise hold relevance for pancreatic and colon cancer.

16.
Cardiovasc Intervent Radiol ; 44(9): 1448-1455, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34180002

RESUMO

PURPOSE: To test a stent-graft specifically designed for the ascending aorta in phantom, cadaver, and clinical application, and to measure deployment accuracy to overcome limitations of existing devices. METHODS: A stent-graft has been designed with support wires to fixate the apices toward the inner curvature, thereby eliminating the forward movement of the proximal end which can happen with circumferential tip capture systems. The device was deployed in three aortic phantoms, and in four cadavers, deployment precision was measured. Subsequently, the device was implanted in a patient to exclude a pseudoaneurysm originating from the distal anastomosis after ascending aortic replacement. RESULTS: The stent-grafts were successfully deployed in all phantoms and cadavers. Deployment accuracy of the proximal end of the stent-graft was within 1 mm proximally and 14 mm distally to the intended landing zone on the inner curvature, and 2-8 mm distal to the intended landing zone on the outer curvature. In clinical application, the pseudoaneurysm could be successfully excluded without complications. CONCLUSION: The novel stent-graft design promises accurate placement in the ascending aorta. The differential deployment of the apices at the inner and outer curvatures allows deployment perpendicular to the aortic axis. LEVEL OF EVIDENCE: No level of evidence.


Assuntos
Stents , Idoso , Aorta/diagnóstico por imagem , Aorta/cirurgia , Prótese Vascular , Implante de Prótese Vascular , Cadáver , Procedimentos Endovasculares , Humanos , Masculino , Desenho de Prótese , Resultado do Tratamento
17.
J Vasc Surg ; 73(6): 2123-2131.e2, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33278536

RESUMO

OBJECTIVE: Infection of prosthetic aortic grafts represents a serious complication with high morbidity and mortality. Replacement with autologous material is recommended; however, in its absence, biological material should be favored. In the present retrospective cohort study, we evaluated the short- and midterm results with the use of commercially available prefabricated bovine pericardium grafts (BPGs) used for the management of aortic graft infection or aortic reconstructive surgery in the presence of systemic infection. METHODS: We performed a retrospective analysis of patients in whom BPGs had been used for aortic reconstruction at two vascular centers. Prefabricated vascular pericardium grafts were preferred over other biological reconstruction techniques for selected cases. Comorbidities, procedure-related details, perioperative morbidity, clinical outcomes, and mortality were analyzed. RESULTS: From 2014 to 2019, 21 patients had received BPGs at two Austrian vascular centers. Their median age was 63 years (interquartile range [IQR], 55-71 years), the patients were predominantly male (76%), and the median body mass index was 25.3 kg/m2 (IQR, 21.7-27.3 kg/m2). The major comorbidities included arterial hypertension, peripheral artery disease, smoking, and chronic pulmonary disease. The indications for surgery were vascular graft or endograft infection in 62% and aortic reconstruction in the presence of systemic infection in 38%. Three patients (14%) had aortoenteric fistulas. Surgery was technically successful in all cases. The median follow-up was 21.6 months (IQR, 6.0-34.6 months). The 30-day mortality was 9.5%. The 1- and 2-year overall survival was 84% and 75%, respectively. Of the 21 patients, 89% had remained free of recurrent infection. One of the two reinfections had resolved after treatment of the underlying focus. At 2 years, the primary and assisted primary patency rates were 86% and 94%, respectively. No limbs were lost during follow-up. CONCLUSIONS: Prefabricated BPGs represent a promising alternative for the management of aortic graft infections and aortoiliac reconstruction in the presence of systemic infection.


Assuntos
Aorta Abdominal/cirurgia , Bioprótese , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular/efeitos adversos , Pericárdio/transplante , Infecções Relacionadas à Prótese/cirurgia , Idoso , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/fisiopatologia , Áustria , Bovinos , Remoção de Dispositivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/fisiopatologia , Reinfecção , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
18.
Case Rep Obstet Gynecol ; 2019: 9461579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281696

RESUMO

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22nd week of gestation.

19.
J Vasc Surg ; 69(2): 318-326, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30683192

RESUMO

OBJECTIVE: This study retrospectively assessed in-hospital mortality and long-term results of emergency thoracic endovascular aortic repair (TEVAR) for patients with life-threatening acute complicated type B aortic dissection (acTBD). METHODS: Between March 2001 and December 2016, there were 55 patients (40 male; median age, 52 ± 13 years) with an acTBD who were treated with TEVAR for malperfusion (58%), aortic rupture (18%), or persistent untreatable pain with true lumen reduction or rapid aortic diameter enlargement (24%) as a sign of disease progression. The patients were categorized according to clinical appearance into two groups: group A, malperfusion, pending rupture, or rupture; and group B, persistent ongoing pain, rapid enlargement of aortic diameter, or significant changes in the true to false lumen ratio. Four patients (7%) had undergone previous aortic surgery. RESULTS: Technical success (coverage of the primary intimal tear) was achieved in 50 patients (91%). The overall in-hospital mortality rate was 9% (n = 5), and there was a statistically significant difference in early mortality between group A and group B (7% vs 2%; P < .02). Causes of in-hospital death were all aorta related, including a rupture during the procedure and on the first postinterventional day in two patients and redissection (ascending aorta, n = 2; descending aorta, n = 1) with a consequent aortic rupture after TEVAR in the remaining three. Permanent neurologic dysfunction occurred in five patients (stroke, n = 2; paraplegia, n = 3). Overall, 19 patients (34%) developed early endoleaks (type IA, n = 5; type IB, n = 11; type II, n = 2; type IB plus type II, n = 1). Therefore, 5 patients needed early (within 30 days) endovascular intervention because of a type IA (n = 2), type IB (n = 3), or type II endoleak (n = 1) and the rapid progression of aortic diameter, persistent signs of ischemia (n = 2), or rupture (n = 1), whereas the remaining 14 patients were treated conservatively and followed up by computed tomography angiography. Seven patients with early endoleaks needed an endovascular intervention (n = 3) or conventional surgery (n = 4) because of aortic progression in the follow-up period (mean interval after procedure, 92 ± 56 months). The actual survival rates were 87%, 85%, and 75% at 1 year, 2 years, and 5 years, respectively, and freedom from aorta-related death was 87%, 87%, and 77% at 1 year, 2 years, and 5 years, respectively. Freedom from reintervention for any cause using a Kaplan-Meier analysis was 70%, 68%, 68%, and 63% at 6 months, 1 year, 2 years, and 5 years, respectively. CONCLUSIONS: TEVAR of acTBD has been proven to be an excellent treatment modality in this cohort of high-risk patients, with promising midterm and long-term results.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Doença Aguda , Adulto , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Dissecção Aórtica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Progressão da Doença , Emergências , Endoleak/etiologia , Endoleak/mortalidade , Endoleak/terapia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Am J Phys Med Rehabil ; 97(9): 651-658, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29613883

RESUMO

OBJECTIVE: The aim of the study was to follow both the structure- and function-related long-term course of shoulders that had been treated with therapeutic ultrasound for symptomatic calcific tendinitis. DESIGN: This is a long-term follow-up of 45 shoulders (37 patients) that had been treated for symptomatic calcific tendinitis with either a series of ultrasound or sham ultrasound 10 yrs ago. The main outcome variables were presence of calcium deposits and subacromial impingement on standardized x-ray imaging, shoulder symptoms (Binder score), and function (Constant score). RESULTS: At 10 yrs, a similar proportion of calcium deposits had resolved in 78% of the originally ultrasound treated compared with 83% of sham-treated shoulders, whereas at 9 mos, significantly more calcium deposits had been resolved in the ultrasound group (P = 0.045). Relative to baseline, shoulder symptoms and function had significantly improved at both the 10-yr and 9-mo follow-up examinations with no significant differences between groups. Regular sports performance at baseline predicted a favorable long-term outcome. CONCLUSIONS: Symptomatic calcific tendinitis of the shoulder has a good likelihood to completely resolve in the long term. Treating the calcium deposit effectively, however, may not be causal to the recovery from symptoms and function in calcific tendinitis.


Assuntos
Calcinose/terapia , Síndrome de Colisão do Ombro/terapia , Articulação do Ombro/fisiopatologia , Tendinopatia/terapia , Terapia por Ultrassom , Adulto , Idoso , Índice de Massa Corporal , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Recidiva , Síndrome de Colisão do Ombro/fisiopatologia , Articulação do Ombro/diagnóstico por imagem , Dor de Ombro/fisiopatologia , Dor de Ombro/terapia , Esportes , Tendinopatia/fisiopatologia
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