RESUMO
Early recognition of vulnerable carotid plaques could help in identifying patients at high stroke risk, who may benefit from earlier revascularisation. Nowadays, different biomarkers of plaque instability have been unravelled, among these miRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression. The goal of the present study was to determine whether miR-200c could be an atherosclerosis biomarker. Carotid plaques of patients that underwent carotid endarterectomy (CEA) were assayed for miR-200c expression. miR-200c was up-regulated in carotid plaques (n=22) and its expression was higher in unstable (n=12) compared with stable (n=10) plaques. miR-200c positively correlated with instability biomarkers (i.e. monocyte chemoattractant protein-1, cicloxigenase-2 (COX2), interleukin 6 (IL6), metalloproteinase (MMP) 1 (MMP1), 9 (MMP9)) and miR-33a/b. Moreover, miR-200c negatively correlated with stability biomarkers (i.e. zinc finger E-box binding homoeobox 1 (ZEB1), endothelial nitric oxide (NO) synthase (eNOS), forkhead boxO1 (FOXO1) and Sirtuin1 (SIRT1)) (stable plaques = 15, unstable plaques = 15). Circulating miR-200c was up-regulated before CEA in 24 patients, correlated with miR-33a/b and decreased 1 day after CEA. Interestingly, 1 month after CEA, circulating miR-200c is low in patients with stable plaques (n=11) and increased to control levels, in patients with unstable plaques (n=13). Further studies are needed to establish whether miR-200c represents a circulating biomarker of plaque instability. Our results show that miR-200c is an atherosclerotic plaque progression biomarker and suggest that it may be clinically useful to identify patients at high embolic risk.
Assuntos
Artérias Carótidas/patologia , Estenose das Carótidas/genética , MicroRNAs/genética , Placa Aterosclerótica , Idoso , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos , Humanos , Masculino , MicroRNAs/sangue , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Fatores de Tempo , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: The aim of this study is to analyze the effects of peripheral blood mononuclear cells (PBMNCs) therapy in diabetic patients with critical limb ischemia (CLI), with particular regard to its application, as adjuvant therapy in patients underwent endovascular revascularization. METHODS: Fifty diabetic patients affected by CLI were enrolled. All patients underwent PBMNCs therapy. Thirty-two patients underwent PBMNCs therapy associated with endovascular revascularization (adjuvant therapy group). In 18 patients, who were considered nonrevascularizable or underwent unsuccessful revascularization, regenerative therapy with PBMNCs was performed as the therapeutic choice (PBMNCs therapy group). RESULTS: The median follow-up period was 10 months. The baseline and end point results in adjuvant group were as follows. The mean transcutaneous partial pressure of oxygen (TcPO2) improved from 25 ± 9.2 mmHg to 45.6 ± 19.1 mmHg (P < 0.001), and visual analogue scale (VAS) score means decreased from 8.6 ± 2.1 to 3.8 ± 3.5 (P = 0.001). In PBMNCs therapy group, the mean TcPO2 improved from 16.2 ± 7.2 mmHg to 23.5 ± 8.4 mmHg (P < 0.001), and VAS score means decreased from 9 ± 1.1 to 4.1 ± 3.3 (P = 0.001). Major amputation was observed in 3 cases (9.4%), both in adjuvant therapy group and in PBMNCs therapy one (16.7%) (P = 0.6). CONCLUSIONS: The role of cellular therapy with PBMNCs is decisive in the patients that are not susceptible to revascularization. In diabetic patients with CLI and healing resistant ulcers, the adjuvant PBMNCs therapy could represent a valid therapeutic option.
Assuntos
Procedimentos Endovasculares , Úlcera do Pé/cirurgia , Isquemia/cirurgia , Leucócitos Mononucleares/transplante , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Estado Terminal , Progressão da Doença , Feminino , Úlcera do Pé/diagnóstico por imagem , Úlcera do Pé/fisiopatologia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Cidade de Roma , Fatores de Tempo , Resultado do Tratamento , CicatrizaçãoRESUMO
Aim: To assess the medium and long-term performance of the Endurant stent graft in a cohort of consecutive patients treated with this device for an abdominal aortic aneurysm (AAA) both inside and outside of the instructions for use (IFU) and to find factors influencing the outcomes. Methods: Our observational, retrospective, single-center study included all patients who consecutively underwent endovascular aneurysm repair with the Endurant stent graft from February 2009 to January 2023. Patients with an AAA to treat according to current guidelines were included. Patients were divided into two groups: Group 1 inside of the IFUs and Group 2 outside of the IFUs for the proximal aortic neck. Patients were followed up after the procedure with computed angiography tomography, ultrasound examination, and interviews. Aneurysm-related mortality, procedure-related reinterventions, and type IA and III endoleaks were considered primary endpoints. Secondary endpoints included aneurysmal sac variations and graft thrombosis. Results: A total of 795 patients were included, 650 in Group 1 and 145 in Group 2; 732 were males, and the mean age was 74 ± 8. Anamnestic baseline did not differ between the two groups. Neck length, width, and angulation were different between the two groups (all p < 0.001). A total of 40 patients had a ruptured AAA, while 56 were symptomatic. At a mean follow-up of 43 ± 39 months, aneurysm-related mortality was less than 1%, and 82 endoleak (10.5%) were observed. Overall endoleak rate and type 1A endoleak, as well as procedure-related reintervention, were significantly more frequent in Group 2. Sac regression of at least 5 mm was observed in 65.9% of cases. AAAs larger than 60.5 mm carried a higher risk of endoleak (HR: 1.025; 95% CI: 1.013-1.37; p < 0.001) and proximal necks shorter than 13.5 mm carried a higher type 1A risk (HR: 0.890; 95% CI: 0.836-0.948; p < 0.001). Patients without chronic obstructive pulmonary disease and taking lipid-lowering drugs had an overall more consistent sac-shrinking rate. Conclusions: The Endurant stent graft proves safe and reliable. Out-of-IFU treatment has poorer medium and long-term outcomes. Some conditions influence medium and long-term reintervention risk and sac behavior. Patients with bigger aneurysms, proximal necks shorter than 13.5 mm, and chronic obstructive pulmonary disease should be more carefully evaluated during follow-up. Consistent follow-up is in keeping low aneurysm-related mortality. Personalized risk profiles and peri and postoperative management strategies are needed.
RESUMO
Cell therapy is becoming an attractive alternative for the treatment of patients with nooption critical limb ischemia (CLI). The main benefits of cell therapy are the induction of therapeutic angiogenesis and neovascularization that lead to an increase in blood flow in the ischemic limb and tissue regeneration in nonhealing cutaneous trophic lesions. In the present review, the current state of the art of strategies in the cell therapy field are summarized, focusing on intraoperative autologous cell concentrates in diabetic patients with CLI, examining different sources of cell concentrates and their mechanisms of action. The present study underlined the detrimental effects of the diabetic condition on different sources of autologous cells used in cell therapy, and also in delaying wound healing capacity. Moreover, relevant clinical trials and critical issues arising from cell therapy trials are discussed. Finally, the new concept of cell therapy as an adjuvant therapy to increase wound healing in revascularized diabetic patients is introduced.
Assuntos
Isquemia Crônica Crítica de Membro/terapia , Complicações do Diabetes/terapia , Animais , Transplante de Células/métodos , Isquemia Crônica Crítica de Membro/etiologia , Complicações do Diabetes/etiologia , Humanos , Transplante Autólogo/métodos , Resultado do Tratamento , CicatrizaçãoRESUMO
Evaluation of the outcomes of OSES (oval-shaped external support), a novel device for external valvuloplasty of the great saphenous vein (GSV) for the conservative treatment of superficial venous insufficiency. Between 2012 and 2015, 30 patients underwent external valvuloplasty of the GSV for a total of 32 limbs. Patients were subjected to clinical and instrumental follow-up by a half-year ultrasound for a minimum of 36 months. The main endpoints were the recurrence of varicose disease, persistent or recurrent venous reflux, and venous thrombosis. Varicose recurrence was verified in six limbs on 32 (18.75%). Four limbs (12.5%) presented a recurrence of the reflux even in the absence of varicose veins. Two limbs (6.25%) underwent saphenectomy after the valvuloplasty intervention at 12 and 18 months, respectively, because of the presence of saphenofemoral reflux and varicose recurrences. No case of venous thrombosis of the saphenous trunk was observed. The external valvuloplasty of the GSV is a well-known technique that used to treat the superficial venous insufficiency. The newly introduced OSES device seems to show better midterm results, due to a better alignment of the valve flaps. In our experience, the use of this device gives better long-term results and allowed to extend the indication to patients with saphenic diameters that were considered not eligible for repair. In conclusion, although our data needs further confirmation, OSES device might represents a new interesting opportunity for reconstructive venous surgery.
RESUMO
PURPOSE: Multiple treatment options have been described for intramuscular venous malformations (VMs) of the limbs. At the current time, there are no clear management guidelines. The aim was to evaluate efficacy and safety of sclerotherapy in this type of VMs. MATERIALS AND METHODS: This is a single-center, retrospective review of patients treated for extremity intramuscular VMs between January 2013 and June 2017. The primary outcomes were the improvement of symptoms self-assessed by questionnaires, and the reduction in VM size measured by magnetic resonance (MRI). RESULTS: Sclerotherapy was performed in 81 patients with extremity intramuscular VMs. The sclerosing agent was ethanol in 46 cases (56.8%), polidocanol in 27 cases (33.3%), a combination of both in 8 cases (9.9%). The mean follow-up was 26 months (range 3-52). Overall quality of life was improved in 62 patients (76.5%). The postoperative MRI showed a minimum change of VM size in 68 patients (83.9%). A major complication (peripheral nerve injury) was observed in 1 case (1.2% of patients, 0.5% of procedures). Minor complications occurred in 9 cases (11.1% of patients, 4.1% of procedures). CONCLUSIONS: Sclerotherapy is a low-invasive, effective and safe treatment for intramuscular VMs of the extremities. It induces a significant improvement in symptoms, also when the VM size is unchanged. LEVEL OF EVIDENCE: Level 4, Case Series.