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Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7 days following pPCI) or delayed (> 7 days following pPCI) on-pump CABG surgery were included. All study patients were preloaded with ticagrelor 180 mg prior to pPCI procedure. Patients' demographics, clinical variables, and short-term cardiovascular outcomes were recorded. This is a retrospective study which included 98 patients. Fifty-four (54%) patients underwent early and 44 (45%) patients underwent delayed CABG surgery. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p: 0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level < 10.9 and use of mechanical cardiac support devices were independent predictors of CABG-related bleeding [OR: 3719, p: 0.009 and OR: 11,698, p: 0.004, respectively].There were three deaths within the 30 days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Our results indicated that discontinuation of ticagrelor therapy 3 days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events.
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BACKGROUND: Despite advancements in diagnostic methods and emergency interventions, mortality rates of ruptured abdominal aortic aneurysm (rAAA) continue to remain high. To address this issue, the resuscitative endovascular balloon occlusion of the aorta (REBOA) technique has been designed to provide temporary control of bleeding. We aimed to compare the impact of the REBOA technique during open aortic surgery for rAAA. METHODS: Between January 2014 and November 2021, 53 consecutive patients (46 males, 7 females; mean age 71.9 ± 7.9 years; range 51-89 years) who underwent emergency open aortic surgery for rAAA were retrospectively analyzed. Patients were divided into REBOA (21 patients) and non-REBOA (32 patients) groups. The primary outcomes were postoperative 24-hr and 30-day mortality. The secondary outcomes were intensive care unit (ICU) stay, in-hospital stay, bleeding, postoperative renal failure, bowel ischemia, and transient ischemic attack (TIA)/stroke rate. RESULTS: The REBOA group showed a significant reduction in mortality rates at both 24 hr (9.5% vs. 37.5%, P = 0.029) and 30 days (14.2% vs. 43.7%, P = 0.035) compared to the non-REBOA group. In-hospital stay (12.8 ± 3.48 vs. 15.6 ± 4.74 days, P = 0.02) and ICU stay (2.42 ± 2.08 vs. 5.09 ± 5.79 days, P = 0.048) were shorter among the REBOA group. Total procedure time and bleeding were reduced among the REBOA group without significant differences in terms of postoperative renal failure, bowel ischemia, and TIA/stroke rate. CONCLUSIONS: The REBOA group demonstrated significantly improved survival rates compared to the non-REBOA group, without a significant difference in complication rates. REBOA is considered a less invasive option compared to the traditional method for open aortic cross-clamping. This study demonstrated that the use of REBOA may be considered as a first-line treatment option for open surgery in cases of rAAA particularly when an off-the-shelf endovascular aneurysm repair device is not suitable.
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Aneurisma de la Aorta Abdominal , Rotura de la Aorta , Oclusión con Balón , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Ataque Isquémico Transitorio , Insuficiencia Renal , Accidente Cerebrovascular , Traumatismos Torácicos , Lesiones del Sistema Vascular , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Estudios Retrospectivos , Ataque Isquémico Transitorio/etiología , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Aorta/cirugía , Hemorragia/etiología , Oclusión con Balón/efectos adversos , Oclusión con Balón/métodos , Traumatismos Torácicos/cirugía , Accidente Cerebrovascular/etiología , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/cirugía , Rotura de la Aorta/etiología , Lesiones del Sistema Vascular/cirugía , Insuficiencia Renal/etiología , Isquemia/cirugíaRESUMEN
Background: Deep vein thrombosis of the lower extremities is associated with a significant burden of comorbidities. Objectives: In this study, our objective was to investigate the presence of seasonal variation in deep vein thrombosis (DVT) and assess the location of the thrombus. Methods: Out of 8177 patients admitted to two university hospitals and referred to outpatient clinics, we included a total of 611 consecutive patients (316 females, 295 males) diagnosed with acute deep vein thrombosis in this retrospective study. The mean age of the patients was 59.35±18.49 years, ranging from 1 to 96 years. Patients were categorized into four groups by age. Results: DVT was found to be more frequent in the summer (n = 190 or 31%, p = 0.003) and specifically in August (n = 65 or 10.6%, p = 0.014), while it was least frequent in the spring (n = 128 or 20.9%) and in May (n = 40 or 6.5%). However, when comparing seasons, no significant differences were observed in terms of seasonal variation (p = 0.062) or monthly variation (p = 0.143). Conclusions: Contrary to previous studies, this study demonstrated a higher occurrence of DVT during the summer, particularly in August. However, it did not reveal a clear seasonal pattern. One plausible explanation for these findings could be the adverse winter conditions and transportation challenges within the province, which may result in fewer DVT patients being able to reach hospitals for timely treatment.
Contexto: A trombose venosa profunda (TVP) dos membros inferiores está associada a uma carga significativa de comorbidades. Objetivos: Investigar a presença de variação sazonal na TVP e identificar a localização do trombo. Métodos: Dos 8.177 pacientes internados em dois hospitais universitários e encaminhados para ambulatórios, incluímos um total de 611 pacientes consecutivos (316 mulheres, 295 homens) diagnosticados com TVP aguda neste estudo retrospectivo. A idade média dos pacientes foi de 59,35±18,49 anos, variando de 1 a 96 anos. Os pacientes foram categorizados em quatro grupos com base na idade. Resultados: A TVP foi mais frequente no verão (n = 190 ou 31%, p = 0,003), especificamente em agosto (n = 65 ou 10,6%, p = 0,014), e menos frequente na primavera (n = 128 ou 20,9%) e em maio (n = 40 ou 6,5%). No entanto, ao comparar as estações, não foram observadas diferenças significativas em termos de variação sazonal (p = 0,062) e variação mensal (p = 0,143). Conclusões: Ao contrário de estudos anteriores, este estudo demonstrou maior ocorrência de TVP no verão, principalmente em agosto. No entanto, não revelou um padrão sazonal claro. Explicações plausíveis para essas descobertas seriam as condições adversas do inverno e dificuldades de deslocamento, o que pode resultar em menos pacientes com TVP chegando aos hospitais para tratamento oportuno.
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OBJECTIVES: We investigated cardiovascular surgical interventions in a group of patients with Takayasu's arteritis (TAK) diagnosed and followed by a single centre. METHODS: . Twenty patients with TAK (5 males, 15 females, mean current age: 38.1±10.7) who were operated for a broad spectrum of cardiovascular diseases ranging from coronary heart disease to coeliac stenosis or aneurysm between July 2008 and April 2016 were studied. One patient underwent operation related to aneurysm of ascending aorta and aortic insufficiency, 2 patients had operations for both coronary arteries originating from aortic arch, 6 patients for only arteries originating from aortic arch, 1 patient for both carotid and infra-inguinal artery, 5 patients for aorta-iliac or femoral revascularisation, 5 patients for renal artery and/or coeliac or superior mesenteric artery revascularisations. Three of these interventions were endarterectomy and patch plasty. RESULTS: The mean time between diagnosis and surgical intervention was 6.1±3.1 years (range: 3 months-12 years). A total of 4/32 (12.5%) grafts were occluded during the follow up period of mean 39.2±24.6 months. Secondary interventions like cross-femoral, or graft to superficial femoral artery bypasses were needed in 2 patients who underwent aorta-bifemoral bypasses to keep patency. There was no operative mortality. We did not observe any anastomotic aneurysm. One patient died due to graft infection 3 months after the operation. Stroke occurred in 2 patients who underwent re-vascularisations of the arteries originating from aortic arch. CONCLUSIONS: In our series, we have a relatively good midterm patency rates in patients with TAK and did not observe any anastomotic pseudoaneurysm. Stroke developed in 2 patients and mortality occurred in one patient due to the graft infection 3 months after the operation. In patients with limited carotid or aorta-iliac stenosis, chance for endarterectomy should be evaluated. Well-controlled disease activity with intensive medical treatment and multi-disciplinary approach could be associated with a favourable long-term outcome.
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Arteritis de Takayasu/cirugía , Procedimientos Quirúrgicos Vasculares , Adulto , Aorta/cirugía , Femenino , Arteria Femoral/cirugía , Humanos , Masculino , Persona de Mediana Edad , Arteria Renal/cirugíaRESUMEN
Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.
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LDL-Colesterol/sangre , Interleucina-18/genética , Enfermedad Arterial Periférica/genética , ARN Mensajero/genética , Triglicéridos/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Interleucina-18/sangre , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Proyectos Piloto , Polimorfismo de Nucleótido Simple , ARN Mensajero/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Turquía , Regulación hacia ArribaRESUMEN
Behçet's syndrome (BS) is a systemic inflammatory disease generally presented with triad of uveitis, oral and genital ulcers. However, it may present with gastrointestinal, central nervous system, skin, vascular disease manifestations. Cardiac involvement like intracardiac thrombus and valvular involvement in BS are rarely seen entities. Here we present the management of a 23-year old male BS patient who had a right ventricular thrombus and tricuspid valve dysfunction which was resistant to immunosuppressive treatment. He has been doing well for 4 years after intraventricular thrombus resection and tricuspid valve replacement with bioprosthesis.
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Síndrome de Behçet/complicaciones , Cardiopatías/etiología , Trombosis/etiología , Insuficiencia de la Válvula Tricúspide/etiología , Síndrome de Behçet/patología , Cardiopatías/patología , Ventrículos Cardíacos/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Trombosis/patología , Insuficiencia de la Válvula Tricúspide/patología , Adulto JovenRESUMEN
Introduction: Studies searching outcomes of eversion carotid endarterectomy (E-CEA) under local anesthesia are lacking. Aim: To evaluate the postoperative outcomes of E-CEA under local anesthesia and compare it with E-CEA/Conventional CEA under general anesthesia in symptomatic or asymptomatic patients. Material and methods: From February 2010 to November 2018 a total of 182 patients (143 males, 39 females; mean age: 69.69 ±9.88 years; range: 47 to 92 years) who underwent eversion CEA or conventional CEA with patchplasty under general or local anesthesia in two tertiary centers were included in this study. Results: Overall in-hospital stay (p = 0.01), postoperative in-hospital stay (p = 0.022) took significantly less time in favor of E-CEA under local anesthesia. Overall, 6 patients developed major stroke (3.2%), among them 4 (2.1%) patients passed away, 7 (3.8%) patients developed cranial nerve injury (the marginal mandibular branch of the facial nerve and hypoglossal nerve), 10 (5.4%) patients developed a hematoma in the postoperative period. No difference was found in terms of postoperative stroke (p = 0.470), postoperative death (p = 0.703), postoperative bleeding rate (p = 0.521) or postoperative cranial nerve injury (p = 0.481) between the groups. Conclusions: The mean operation time, postoperative in-hospital stay, overall in-hospital stay, and need for shunting were lower in patients who underwent E-CEA under local anesthesia. E-CEA under local anesthesia seemed to do better in stroke, death, and bleeding rate, however, this difference was not significant.
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BACKGROUND: Aortic valve diseases are life-threatening conditions with increasing prevalence worldwide. Risk factors include gender, age, hypertension, dyslipidemia, and type 2 diabetes. Obesity is closely related to these risk factors and has been linked to a higher risk of developing aortic valve diseases. However, there is no specific guideline for managing aortic valve disease in patients with obesity, and the choice of valve type remains uncertain. METHODS: A total of 130 patients with obesity who met the inclusion criteria underwent surgical aortic valve replacement. The patients were divided into two groups based on the type of prosthesis used. Among the study cohort, 50 patients received a bioprosthetic valve, while 80 patients received a mechanical valve. We compared these groups in terms of perioperative characteristics and follow-up results. Statistical significance was determined using a p-value threshold of 0.05. RESULTS: There were no significant differences in age, gender, body mass index, or cardiac comorbidities between the two groups. Preoperative blood results and echo findings also showed no significant differences. Intraoperative characteristics and postoperative outcomes, including mortality and acute kidney injury, did not differ significantly between the groups. In addition, BHVG patients had shorter ICU stays compared to MHVG patients without significance. CONCLUSION: Deliberate consideration is crucial when selecting valves for obese patients, particularly those with class II obesity. This is due to the potential influence of obesity on valve types, as well as the need to account for the possibility of bariatric surgery and its potential effects.
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Enfermedad de la Válvula Aórtica , Bioprótesis , Diabetes Mellitus Tipo 2 , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/cirugía , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/cirugía , Obesidad/complicaciones , Obesidad/diagnóstico , Enfermedad de la Válvula Aórtica/etiología , Enfermedad de la Válvula Aórtica/cirugía , Diseño de Prótesis , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: In this single-center study, we analyzed a retrospective cohort of patients with diabetic foot infections (DFIs) between 2011 and 2020. Patients and Methods: The first and second five-year periods were compared. A poor prognosis was defined as a primary composite end point including re-infection, major amputation, or mortality at six months. Results: A total of 484 patients were enrolled. Overall, 269 patients had the primary composite end point. A substantial decrease was detected in the second five-year period in terms of re-infection (n = 132, 66.0% vs. n = 68, 23.9%; p < 0.001) and mortality (n = 22, 11.0% vs. n = 7, 2.5%; p < 0.001). A total of 798 micro-organisms were isolated from 484 patients. A substantial increase was detected in polymicrobial infections (48.5% vs. 65.1%; p = 0.001) as well as Streptococcus spp. (2.5% vs. 9.2%; p = 0.003), Corynebacterium spp. (9.5% vs. 22.9%; p < 0.001), and extended-spectrum ß-lactamase (ESBL) producing Escherichia coli (3.0% vs. 12.7%; p < 0.001) in the second five-year period, whereas the prevalence of multi-drug-resistanct (MDR) Pseudomonas aeruginosa (17.0% vs. 10.2%; p = 0.029) and carbapenem-resistant Acinetobacter baumannii (7.5% vs. 2.8%; p = 0.017) decreased. Multivariable regression analysis revealed that MDR Pseudomonas aeruginosa (odds ratio [OR], 1.917; 95% confidence interval [CI], 1.074-3.420; p = 0.028) and carbapenem-resistant Acinetobacter baumannii (OR, 3.069; 95% CI, 1.114-8.453; p = 0.030) were independent predictors for poor prognosis. Conclusions: This 10-year cohort study provides reassuring information about the changing epidemiology of DFIs and the prognostic determinants in patients with DFIs.
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Acinetobacter baumannii , Diabetes Mellitus , Pie Diabético , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Carbapenémicos , Estudios de Cohortes , Pie Diabético/epidemiología , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Humanos , Pruebas de Sensibilidad Microbiana , Pronóstico , Pseudomonas aeruginosa , Reinfección , Estudios RetrospectivosRESUMEN
INTRODUCTION: Multiple rib fractures exposes serious respiratory disorders and they are generally treated with non surgical methods. Nevertheless, in cases of long term pain despite medical treatment, parenchymal injury, hematoma, posture disorder and flail chest, surgery is needed. Flail chest, as the most critical form of blunt chest trauma, can disturb the hemodynamic of patient significantly and threaten life. This work has been reported in line with the SCARE criteria. PRESENTATION OF CASE: A 32 year old male patient referred to our hospital with flail chest in intubated status due to industrial accident. In physical examination, there was displaced dissociation in lower 1/3 of sternum and pericardium was palpated in the subcutaneus tissue. In thorax CT, there was fracture both in the right 7-8. costochondral and in the left 8. costochondral joints. Additionally, crepitation was palpated in these joints. There was flail chest in the right anterior hemithorax and in the lower sternum. Patient was treated with chest wall reconstruction with titanium plaques. DISCUSSION: In cases of flail chest, after a few days mechanical ventilation, implementing stabilization provides a rapid healing. CONCLUSIONS: We believe there is significant place of surgery for stabilization in proper cases.
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Abstract Background Deep vein thrombosis of the lower extremities is associated with a significant burden of comorbidities. Objectives In this study, our objective was to investigate the presence of seasonal variation in deep vein thrombosis (DVT) and assess the location of the thrombus. Methods Out of 8177 patients admitted to two university hospitals and referred to outpatient clinics, we included a total of 611 consecutive patients (316 females, 295 males) diagnosed with acute deep vein thrombosis in this retrospective study. The mean age of the patients was 59.35±18.49 years, ranging from 1 to 96 years. Patients were categorized into four groups by age. Results DVT was found to be more frequent in the summer (n = 190 or 31%, p = 0.003) and specifically in August (n = 65 or 10.6%, p = 0.014), while it was least frequent in the spring (n = 128 or 20.9%) and in May (n = 40 or 6.5%). However, when comparing seasons, no significant differences were observed in terms of seasonal variation (p = 0.062) or monthly variation (p = 0.143). Conclusions Contrary to previous studies, this study demonstrated a higher occurrence of DVT during the summer, particularly in August. However, it did not reveal a clear seasonal pattern. One plausible explanation for these findings could be the adverse winter conditions and transportation challenges within the province, which may result in fewer DVT patients being able to reach hospitals for timely treatment.
Resumo Contexto A trombose venosa profunda (TVP) dos membros inferiores está associada a uma carga significativa de comorbidades. Objetivos Investigar a presença de variação sazonal na TVP e identificar a localização do trombo. Métodos Dos 8.177 pacientes internados em dois hospitais universitários e encaminhados para ambulatórios, incluímos um total de 611 pacientes consecutivos (316 mulheres, 295 homens) diagnosticados com TVP aguda neste estudo retrospectivo. A idade média dos pacientes foi de 59,35±18,49 anos, variando de 1 a 96 anos. Os pacientes foram categorizados em quatro grupos com base na idade. Resultados A TVP foi mais frequente no verão (n = 190 ou 31%, p = 0,003), especificamente em agosto (n = 65 ou 10,6%, p = 0,014), e menos frequente na primavera (n = 128 ou 20,9%) e em maio (n = 40 ou 6,5%). No entanto, ao comparar as estações, não foram observadas diferenças significativas em termos de variação sazonal (p = 0,062) e variação mensal (p = 0,143). Conclusões Ao contrário de estudos anteriores, este estudo demonstrou maior ocorrência de TVP no verão, principalmente em agosto. No entanto, não revelou um padrão sazonal claro. Explicações plausíveis para essas descobertas seriam as condições adversas do inverno e dificuldades de deslocamento, o que pode resultar em menos pacientes com TVP chegando aos hospitais para tratamento oportuno.
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Background: Carotid artery stenosis is the atherosclerotic narrowing of the proximal internal carotid artery and one of the primary causes of stroke. Elevated expression of the pleiotropic proinflammatory cytokine interleukin-18 has been demonstrated in human atherosclerotic plaques. Aims: To investigate whether the mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 −137 G/C (rs187238) variants are associated with carotid artery stenosis development. Study Design: Case-control study. Methods: The mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 rs187238 variants were evaluated by quantitative real-time polymerase chain reaction and real-time polymerase chain reaction, respectively, in the peripheral blood mononuclear cells of 70 patients with carotid artery stenosis (36 symptomatic, 34 asymptomatic) and 75 healthy controls. Results: Interleukin-18 mRNA expression was significantly increased in carotid artery stenosis patients compared to that in healthy controls (p=0.01). However, no significant difference was observed between interleukin-18-binding protein mRNA expression levels in patients with carotid artery stenosis and those in controls (p=0.101). Internal carotid artery stenosis severity was significantly higher in symptomatic patients than that in asymptomatic patients (p<0.001). A significant relationship was identified between interleukin-18 expression and internal carotid artery stenosis severity in patients with carotid artery stenosis (p=0.051). Interleukin-18 rs187238 polymorphism genotype frequencies did not significantly differ between patients with carotid artery stenosis and controls (p=0.246). A significant difference was identified between interleukin-18-binding protein gene expression and symptomatic and asymptomatic patients (p=0.026), but there was no difference in interleukin-18 expression between the symptomatic and asymptomatic subgroups (p=0.397). Conclusion: Interleukin-18 mRNA expression may affect carotid artery stenosis etiopathogenesis and internal carotid artery stenosis severity and also may play a mechanistic role in the pathogenesis of carotid artery stenosis, influencing the appearance of symptoms.
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Estenosis Carotídea/genética , Interleucina-18/genética , ARN Mensajero/genética , Adulto , Anciano , Anciano de 80 o más Años , Estenosis Carotídea/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular , Interleucina-18/metabolismo , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , TurquíaRESUMEN
Atherosclerosis (AT) is a chronic immuno-inflammatory disease characterized by inflammatory mediators and immune activation in arterial wall. Although NF-κB and microRNAs are involved in the atherosclerotic lesions, the pathogenesis of atherosclerosis is still unknown. The aim of this study was to investigate the association of atherosclerosis with NFKB1-rs28362491, NFKBIA-rs696, pre-miRNA-146a-rs2910164 and pre-miRNA-499-rs3746444 polymorphisms as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. We analysed the distribution of NFKB1-94 ins/del ATTG (rs28362491), NFKBIA (rs696), pre-miR-146a (rs2910164) and pre-miR-499 (rs3746444) genetic polymorphisms using PCR-RFLP assay in 150 atherosclerotic patients and 145 healthy controls in a Turkish population. The data revealed no significant differences in the distribution of the genotype and alleles of rs28362491 ,whereas AA genotype of rs696 lead to a higher risk for atherosclerotic patients. TT genotype and T allele of pre-miR-499 rs3746444 were found to be associated with atherosclerosis risk. In addition, significant differences were found between atherosclerotic patients and control subjects, concerning pre-miR-146a rs2910164 polymorphism. The subjects carrying the GG genotype and G allele of rs2910164 were found to have an increased risk against AT. The results of combined genotype analysis, showed no notable differences between the multiple comparisons of rs28362491- rs696 whereas rs28362491-rs2910164 ins/ins/GG is associated with increased AT risk. The combined genotypes of rs28362491/rs3746444 ins/ins/TT, revealed a significant protective effect on AT. These findings indicate that genetic polymorphisms of NFKB1A rs696, pre-miR-146a rs2910164 and pre-miR-499 rs3746444 may represent novel markers of AT susceptibility.
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Aterosclerosis/genética , MicroARNs/genética , Inhibidor NF-kappaB alfa/genética , Adulto , Alelos , Pueblo Asiatico , Aterosclerosis/epidemiología , Aterosclerosis/patología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Turquía/epidemiologíaRESUMEN
AIM: The INK4b-ARF-INK4a locus in the chromosome 9p21 region is known to play an important role in the development of atherosclerosis. The INK4/ARF transcript p16(INK4a) inhibits the activity of the cyclin-dependent kinases CDK4/CDK6 and arrests cell-cycle progression. CDK inhibitors also regulate G1/S phase progression in vascular smooth muscle cells(VSMCs) and may modulate the early stages of atherosclerosis. Therefore, we aimed to study the expression of the INK4/ARF locus genes CDKN2A and CDKN2BAS in order to examine the p16(INK4a) protein expression and the level of cell proliferation in carotid plaques and saphenous tissue samples. METHODS: A total of 50 patients(33 symptomatic subjects and 17 asymptomatic subjects) with carotid atherosclerosis CA) were studied. The CDKN2A and CDKN2BAS gene expression levels were determined using quantitative real-time polymerase chain reaction(qRT-PCR). All tissue sections were also analyzed for the p16(INK4a) and proliferating cell nuclear antigen(PCNA) protein expression using immunohistochemistry(IHC). RESULTS: The CDKN2A gene expression was significantly higher in the carotid plaques than in the saphenous tissues(p=0.009), whereas no such differences were observed in the CDKN2BAS transcripts(p=0.157). The carotid plaque CDKN2A mRNA levels were higher in the symptomatic patients than in the asymptomatic patients(p=0.050); this finding was also associated with the severity of internal carotid artery(ICA) stenosis(p=0.034). The p16(INK4a) immune(ï¼) cell counts in the carotid plaques were higher in the symptomatic patients than in the asymptomatic patients (p=0.056), as was the cell proliferation index(p=0.001). CONCLUSIONS: An increased CDKN2A gene expression in carotid plaques may increase the severity of ICA stenosis, thus raising the risk of atherosclerosis and contributing to the development of symptoms. In addition, the p16(INK4a) expression is associated with carotid atherosclerosis in various patient subgroups.