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Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.
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Cobre , Isquemia , Cobre/metabolismo , Cobre/deficiência , Humanos , Animais , Isquemia/metabolismo , Isquemia/genética , Isquemia/patologia , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Transdução de SinaisRESUMO
PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.
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Glioblastoma , Adulto , Humanos , Masculino , Estudos de Coortes , Glioblastoma/terapia , Estudos Retrospectivos , Japão/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: To estimate the incidences of left renal vein (LRV) entrapment by right renal artery (RRA), a phenomenon primarily reported as case reports. METHODS: The cross-sectional study consecutively screened renal vessel CT data of 38 (Renal) patients with nephropathy and 305 (Non-renal) patients with peripheral arterial diseases in a teaching hospital in northeast China between November 2018 and March 2023. The LRV compression by adjacent anatomical structures, including but not limited to RRA and multiple compression-related parameters, were investigated through multiplanar analysis of the CT data. RESULTS: The overall LRV entrapment rates by adjacent structures were 41.93% (12/31) and 24.00% (6/25), the rates of RRA-sourced LRV compression 22.58% (7/31) and 20.00% (5/25), and the rates of compression by superior mesenteric artery (SMA) 16.13% (5/31) and 4.00% (1/25) in the Renal and Non-renal groups, respectively, with no significance. The venous segments distal to the RRA-compressed site had a significantly larger transectional lumen area than those of the non-compressed veins in both groups (3.09 ± 1.29 vs. 1.82 ± 0.23, p < 0.001 and 4.30 ± 2.65 vs. 2.12 ± 0.55, p = 0.006; maximum-to-minimum area ratios in Renal and Non-renal groups, respectively). Nearly 80% of RRAs were found arising anteriorly rightwards instead of passing straight to the right. CONCLUSION: RRA-sourced LRV compression was not rare, and its incidence was higher than that of the compression by SMA in both patient cohorts. RRA could be a more common compression source than SMA concerning LRV entrapment. Further investigations involving different populations, including healthy individuals, are needed.
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Artéria Renal , Veias Renais , Humanos , Estudos Transversais , Pessoa de Meia-Idade , Masculino , Feminino , Veias Renais/diagnóstico por imagem , Veias Renais/anormalidades , Idoso , Artéria Renal/diagnóstico por imagem , Adulto , Tomografia Computadorizada por Raios X , Síndrome do Quebra-Nozes/complicações , Síndrome do Quebra-Nozes/diagnóstico por imagem , IncidênciaRESUMO
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation. OBJECTIVE: To identify biomarkers for improving the screening of CLI in high-risk people with T2DM. METHODS: We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (1H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1H NMR data. RESULTS: Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values. CONCLUSION: The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed.
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Isquemia Crônica Crítica de Membro , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Isquemia , Metabolômica , Índice Tornozelo-BraçoRESUMO
OBJECTIVES: Outcomes in patients with iliofemoral and concomitant iliofemoral-remote arteriopathies who cannot undergo transfemoral or other alternative transvascular approaches have not been studied so far. This study aimed to evaluate the early and midterm outcomes after transapical (TA)-transcatheter aortic valve implantation (TAVI) in patients with femoral and femoral-remote arteriopathies who cannot undergo transvascular approaches. METHODS: Multimorbid patients with severe aortic stenosis and distinct panarteriopathy underwent TA-TAVI treatment between January 2012 and January 2021 at the authors' institution. Second- and third-generation self- and balloon-expanding valves were used. For patients without arterial access, TA-TAVI was modified to the artery-no-touch technique. RESULTS: Seventy-two consecutive elderly patients (78.2 ± 6.9 years; 73% male) were included in the study. The Society of Thoracic Surgery-Predicted Risk of Mortality score was 7 ± 5%. No procedural deaths or conversion to conventional surgery was registered. The 30-day and midterm mortality rates were 5% and 28%, respectively. The median time of freedom from a composite of death and cardiocerebral adverse events was 34.3 months (95% confidence interval: 17.6-51.1). The rate of moderate/severe paravalvular leakage was 0%. The pacemaker rate was 11%. CONCLUSIONS: TA-TAVI is a safe method with low-rate procedural complications and shows good early and midterm outcomes in patients with extensive panarteriopathy for whom transfemoral and other alternative transvascular approaches are contraindicated or at high interventional risk. The modified artery-no-touch TA-TAVI method is safe and feasible for selected patients with no other possible arterial approach.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Idoso , Valva Aórtica/cirurgia , Feminino , Artéria Femoral/cirurgia , Fluoroscopia , Humanos , Masculino , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the safety and effectiveness of tibiopedal and distal femoral access for retrograde crossing of chronic total occlusion (CTO) in Rutherford stage III to VI peripheral arterial occlusive disease, and to determine factors that correlate with technical success. MATERIAL AND METHODS: One hundred seventy-one consecutive patients were included in this retrospective study. Rutherford stages were III, IV, and V/VI in 24%, 8%, and 67% of patients. Inclusion criteria were CTO at the superficial femoral (SFA), popliteal (PA), and/or below-the-knee (BTK) level, and a failed antegrade treatment followed by a distal retrograde approach. The numbers of occluded vascular levels (OVL), lesion length, degree of calcification, technical success rate, complications, and clinical outcome were noted. RESULTS: OVL were 1 in 72%, 2 in 20%, and 3 in 8% of patients. CTOs were longer than 20 cm in 45.6% of cases and showed severe calcifications in 50.3%. Target vessels for distal access were the distal SFA/PA in 17% and BTK in 83%. The overall technical success rate was 82%. Severe calcification decreased technical success (p = 0.01) despite lesion length and Rutherford stage. Clinical outcome improved in 123/152 patients with a significant increase of the median ABI (N = 158) from 0.53 (interquartile range 0.39 to 0.61) to 0.85 (0.59 to 1.03; p < 0.001). Complications were reported in 7.6% cases with 2.3% related to the distal vascular access. CONCLUSION: The tibiopedal and distal femoral retrograde access presents a safe and effective treatment option of CTOs at the thigh and/or BTK after a failed antegrade attempt improving clinical outcome. Technical success decreased with lesion's degree of calcification. KEY POINTS: ⢠Safety and effectiveness of the tibiopedal and distal femoral access for retrograde crossing of chronic total occlusion. ⢠Target lesion's degree of calcification decreases technical success. ⢠Complications related to the distal vascular access were rare.
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Artéria Femoral , Doença Arterial Periférica , Doença Crônica , Estudos de Coortes , Artéria Femoral/diagnóstico por imagem , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Leg ulcers remain an increased burden to healthcare cost and morbidity in modern society. While most leg ulcers are venous in origin, recognition and prompt identification of concomitant arterial occlusive disease is critical to determine underlying aetiology and subsequent management. This integrative review presents the current evidence to establish the role of modified compression therapy (MCT) in treatment of mixed arterial venous leg ulcers (MAVLU). A literature search was conducted using the electronic databases CINAHL, MEDLINE, PUBMED, and Embase. Ten studies met the eligibility criteria and were subsequently analysed. Our review concludes that MCT, with compression pressures between 20 and 30 mmHg, can promote healing in MAVLU with moderate arterial insufficiency (0.5 ≤ ABPI ≤0.8). If ABPI is <0.5, MCT can be considered once restoration of acceptable ABPI is achieved. Intolerance, lack of response or further deterioration of disease within 3 months should prompt further arterial imaging and intervention. MCT is generally well tolerated with no adverse outcomes reported. A holistic yet individualised approach is vital in order to account for all factors influencing this patient-led decision-making process, ultimately ensuring effective treatment, which improves patient's quality of life and reduces socioeconomic burden of the disease.
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Úlcera da Perna , Úlcera Varicosa , Bandagens Compressivas , Humanos , Úlcera da Perna/terapia , Qualidade de Vida , Úlcera Varicosa/terapia , Veias , CicatrizaçãoRESUMO
BACKGROUND: Arterial diseases represent a severe public health problem in the 21st century. Although men have a higher overall prevalence, reports have suggested that women may exhibit atypical manifestations, be asymptomatic, and have hormonal peculiarities, resulting in worse outcomes and severe emergencies, such as acute limb ischemia (ALI). OBJECTIVES: To analyze the morbidity and mortality profile of ALI emergencies in Brazil between 2008 and 2019. METHODS: An ecological study was carried out with secondary data from SIH/SUS, using ICD-10 code I.74 The proportions of emergency hospital admissions and in-hospital mortality rates (HMR) by gender, ethnicity, and age were extracted from the overall figures. P<0.05 was considered significant. RESULTS: From 2008 to 2019, there were 195,567 urgent hospitalizations due to ALI in Brazil, 111,145 (56.8%) of which were of men. Women had a higher HMR (112:1,000 hospitalizations) than men (85:1,000 hospitalizations) (p<0.05), and a higher chance of death (OR=1.36; p<0.05). Furthermore, mean survival was significantly higher among men (8,483/year versus 6,254/year; p<0.05). Stratified by ethnicity, women who self-identified as white (OR=1.44; p<0.05), black (OR=1.33; p<0.05), and brown (RR=1.25; p <0.05) had greater chances of death than men in the same ethnicity categories. Moreover, women over the age of 50 years had a higher chance of death, with a progressive increment in risk as age increased. CONCLUSIONS: There was a trend to worse prognosis in ALI emergencies associated with women, especially in older groups. The literature shows that the reasons for these differences are still poorly investigated and more robust studies of this relevant disease in the area of vascular surgery are encouraged.
CONTEXTO: Doenças arteriais representam um grave problema de saúde pública no século XXI. Apesar de homens apresentarem maior prevalência geral, estudos sugerem que mulheres podem cursar com quadros assintomáticos, clínica atípica e particularidades hormonais, que resultam em desfechos desfavoráveis e urgências graves, como oclusões arteriais aguda (OAA). OBJETIVOS: Analisar o perfil de morbimortalidade das urgências em OAA no Brasil entre 2008 e 2019. MÉTODOS: Realizou-se estudo ecológico com dados secundários do Sistema de Informações Hospitalares/Sistema Único de Saúde, utilizando-se o código I.74 do Código Internacional de Doenças-10. Dos números absolutos, obteve-se proporções de internamentos de urgência e taxa de mortalidade intra-hospitalar (TMH) por gênero, etnia e idade. Considerou-se p < 0,05 significativo. RESULTADOS: Entre 2008 e 2019, houve 195.567 internamentos de urgência por OAA no Brasil, dos quais 111.145 (56,8%) eram homens. Mulheres tiveram maior TMH (112:1.000 hospitalizações) em comparação a homens (85:1.000 hospitalizações) (p < 0,05), assim como maior chance de morte (odds ratio [OR] = 1,36; p < 0,05). Ademais, a média de sobrevida anual foi maior entre homens do que entre mulheres (8.483/ano vs. 6.254/ano, respectivamente; p < 0,05). Estratificando por etnia, mulheres apresentaram maior chance de óbitos entre brancas (OR = 1,44; p < 0,05), pretas (OR = 1,33; p < 0,05) e pardas (razão de risco [RR] = 1,25; p < 0,05), comparadas a homens das mesmas etnias. Nas análises etárias, mulheres com mais de 50 anos apresentaram maior chance de óbito, com aumento progressivo do risco com o envelhecimento. CONCLUSÕES: Nossas análises comparativas evidenciaram tendência de pior prognóstico nas urgências em OAA associadas a mulheres, sobretudo em grupos de idade avançada. A literatura evidencia que as razões para essas diferenças ainda são pouco estudadas, estimulando investigações mais robustas sobre essa importante casuística da cirurgia vascular.
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A severely calcified lesion is the most challenging entity in endovascular therapy (EVT) for below-the-knee (BTK) arteries. In this report, we introduce a challenging plaque modification technique known as the inner PIERCE technique. A 65-year-old man on hemodialysis with multiple toe ulcerations underwent an EVT for his BTK artery diseases. During EVT, the guidewire passed through the severely calcified posterior tibial and plantar arteries; however, the other devices could not pass through the lesion. Therefore, a novel inner PIERCE technique was performed. After guidewire externalization, an 18G 20 cm needle was advanced from the retrograde approach site, following the guidewire, for percutaneous transhepatic cholangiodrainage (PTCD). The PTCD needle was advanced into the severely calcified plaque using a rotational motion. Finally, the needle could pass through the lesion. After the inner PIERCE technique, an angioplasty was performed with a 2.5 mm balloon. The final angiography showed sufficient blood flow. After the EVT, complete wound healing was achieved in 4 months. This challenging technique may be an additional option for EVT to treat severely calcified BTK arteries.
Assuntos
Procedimentos Endovasculares , Isquemia/terapia , Doença Arterial Periférica/terapia , Calcificação Vascular/terapia , Idoso , Doença Crônica , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Masculino , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/fisiopatologiaRESUMO
BACKGROUND: The presence of obstructive sleep apnea (OSA), a novel cardiovascular risk factor, contributes to the development of peripheral arterial diseases (PAD). There is a lack of data showing how often these diseases coexist. AIMS: The aim of the study was to determine the prevalence of OSA in the population of patients with PAD. METHODS: Patients previously qualified for the first revascularization due to PAD were included in the study. All patients underwent an overnight sleep study to detect OSA. Diagnosis of OSA was made when the apnea-hypopnea index (AHI) was ≥5 per hour. RESULTS: From 141 patients (60% men, age 69.6 ± 9.5 years), OSA was diagnosed in 68 patients (48%). OSA occurred in mild form (5 ≤ AHI < 15/h) in 39 cases (28%), in moderate form (15 ≤ AHI < 30/h) in 21 cases (15%), and in severe form (AHI ≥ 30/h) in 8 cases (6%). Patients without OSA had significantly lower body mass index (BMI; 26.9 ± 5.5 vs. 27.7 ± 5.3 kg/m2, p = 0.01) and lower hip circumference (97.4 ± 11.7 vs. 98.7 ± 7.4, p = 0.04). There were no differences in the distribution of other investigated cardiovascular risk factors and diseases between these groups. There were no significant differences in OSA distribution or its severity between patients with lower extremity artery disease and carotid artery disease. CONCLUSIONS: The prevalence of OSA in patients with PAD is very high, affecting nearly half of the studied population.
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Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/etiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: In primary care, measurement of the ankle-brachial index (ABI) by using hand Doppler is recommended for screening of peripheral arterial disease. Despite being relatively a simple procedure, the ABI is rarely measured in primary care due to unpracticality of the hand Doppler method. Oscillometry is an accessible, reliable, and an easy to use method for the measurement of ABI. With a little training, it can be used by anybody. Aim: The aim of the study is to compare the oscillometric method with a reference test (i.e. hand Doppler) for the screening of peripheral arterial disease (PAD) and arterial stiffness (AS) in primary care. METHODS: A prospective observational diagnostic study was designed. Participants were 45 years of age or older. A survey including demographic data, risk factors, and symptoms of the peripheral arterial disease was applied to the participants besides measuring ABI both by Doppler and oscillometric methods. RESULTS: Three hundred and forty participants included in our study with 59.78 ± 9.8 mean age. 60.9% of the participants were men. Even though the results of the oscillometric calculations were higher, a strong correlation was observed between the measurements of two methods. Using the Doppler-derived ABI, as the gold standard, and 0, 9 as a cutoff point, the sensitivity and specificity of the oscillometric method was 74.4% and 100%, respectively, with an area under the curve of 0.98 (95% CI: 0.96-0.99). CONCLUSION: Oscillometry seemed to be a reliable screening method in primary care both for peripheral arterial disease and AS.
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Índice Tornozelo-Braço/métodos , Oscilometria , Doença Arterial Periférica/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia DopplerRESUMO
BACKGROUND/OBJECTIVE: Endovascular interventions for femoropopliteal (FP) arterial diseases are limited by the development of restenosis. Current drug coated devices are capable of preventing restenosis by releasing antiproliferative agents to the vessel wall. However, default strategies for the treatment of FP diseases remain controversial. The aim of this study was to investigate the efficacy differences between drug eluting stents (DES), covered stents (CS), and other commonly used endovascular treatments in FP lesions, including drug coated balloons (DCBs), bare metal stents (BMS), and percutaneous transluminal angioplasty (PTA). METHODS: A comprehensive network meta-analysis was conducted using data from relevant randomised control trials published up to 16 December 2018. Primary patency and target lesion revascularisation (TLR) at 12 months were set as the primary and secondary end points, respectively. RESULTS: Twenty-eight eligible trials including 4728 patients were selected. DES was ranked as the most effective treatment in the multidimensional analysis of primary patency; however, there was no significant difference in the efficacy of DES and that of CS, DCB, and BMS. However, in short lesions (<10 cm), DES was significantly more effective than DCB (odds ratio 0.35; 95% confidence interval 0.15-0.83). Primary patency at 12 months was significantly lower with PTA. In terms of preventing TLR, DCB was ranked first, followed by DES, CS, BMS, and PTA. TLR was significantly higher with PTA than with other treatment strategies. CONCLUSION: The findings of this network meta-analysis suggest that this is not the appropriate time to identify the best endovascular treatment strategy for the FP segment. DES is effective in maintaining mid-term patency, especially in short lesions, whereas DCB seems more suitable for clinical use.
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Angioplastia , Arteriopatias Oclusivas/cirurgia , Stents Farmacológicos , Artéria Femoral/cirurgia , Oclusão de Enxerto Vascular , Artéria Poplítea/cirurgia , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Angioplastia/métodos , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/etiologia , Humanos , Metanálise em RedeRESUMO
BACKGROUND: Reducing women's cardiovascular risk and the economic costs associated with cardiovascular diseases (CVD) and diabetes (DM) continues to be a challenge. Whether a multifaceted CVD screening programme is beneficial as a preventive strategy in women remains uncertain. The aim of this study was to investigate the prevalence of CVD and DM as well as the acceptability toward screening and preventive actions. METHODS: An observational study was performed among all women born in 1936, 1941, 1946 and 1951 living in Viborg Municipality, Denmark, from October 2011. In total, 1984 were invited to screening for abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), carotid plaque (CP), hypertension (HT), atrial fibrillation (AF), DM and dyslipidaemia. Participants with positive tests were offered prophylactic intervention including follow-up consultations in case of AAA, PAD and/or CP. Participants with AAA ≥ 50 mm were referred to specialists in vascular surgery. Women with AF or potential familial hypercholesterolaemia (FH) were referred to cardiology work-up. RESULTS: Among those invited, 1474 (74.3%) attended screening, but the attendees' share decreased with increasing age groups (p < 0.001). AAA was diagnosed in 10 (0.7%) women, PAD in 101 (6.9%) and CP in 602 (40.8%). The percentage of women with these conditions rose with increasing age group (p < 0.05). Unconfirmed potential HT was observed in 94 (6.4%), unknown AF in 6 (0.4%), DM in 14 (1%) and potential FH in 35 (2.4%). None of these findings differed across age groups. Among the 631 women diagnosed with AAA, PAD and/or CP, 182 (28.8%) were already in antiplatelet and 223 (35.3%) in lipid-lowering therapy prior to screening. Antiplatelet therapy was initiated in 215 (34.1%) and lipid-lowering therapy in 191 (30.3%) women. Initiation of antiplatelet and lipid-lowering therapy was further recommended to 134 (21.2%) and 141 (22.4%) women, respectively, who hesitated to follow the recommendation. CONCLUSIONS: The study recorded an acceptable total attendance rate, even though a significantly lower attendance rate was observed in the eldest women. The identified hesitation towards prophylactic therapy may affect the rationale and effectiveness of CVD screening, and hesitation seems a critical issue that should be addressed in the design of future screening programmes.
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Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Pós-Menopausa , Fatores Etários , Idoso , Doenças Cardiovasculares/terapia , Dinamarca/epidemiologia , Diabetes Mellitus/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Avaliação de Programas e Projetos de Saúde , Encaminhamento e Consulta , Fatores SexuaisRESUMO
OBJECTIVE: Surgical hindlimb ischemia (HLI) in mice has become a valuable preclinical model to study peripheral arterial disease. We previously identified that the different phenotypic outcomes after HLI across inbred mouse strains is related to a region on the short arm of mouse chromosome 7. The gene coding the interleukin-21 receptor (IL-21R) lies at the peak of association in this region. APPROACH AND RESULTS: With quantitative real-time polymerase chain reaction, we found that a mouse strain with a greater ability to upregulate IL-21R after HLI had better perfusion recovery than a strain with no upregulation after HLI. Immunofluorescent staining of ischemic hindlimb tissue showed IL-21R expression on endothelial cells (ECs) from C57BL/6 mice. An EC-enriched fraction isolated from ischemic hindlimb muscle showed higher Il-21R levels than an EC-enriched fraction from nonischemic limbs. In vitro, human umbilical vein ECs showed elevated IL-21R expression after hypoxia and serum starvation. Under these conditions, IL-21 treatment increased cell viability, decreased cell apoptosis, and augmented tube formation. In vivo, either knockout Il21r or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) in C57BL/6 mice resulted in less perfusion recovery after HLI. Both in vitro and in vivo modulation of the IL-21/IL-21R axis under hypoxic conditions resulted in increased signal transducer and activator of transcription 3 phosphorylation and a subsequent increase in the B-cell lymphoma leukemia-2/BCL-2-associated X protein ratio. CONCLUSION: Our data indicate that IL-21R upregulation and ligand activation in hypoxic ECs may help perfusion recovery by limiting/preventing apoptosis and favoring cell survival and angiogenesis through the signal transducer and activator of transcription 3 pathway.
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Membro Posterior/irrigação sanguínea , Isquemia/genética , Receptores de Interleucina-21/genética , Animais , Apoptose/genética , Hipóxia Celular/fisiologia , Sobrevivência Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Isquemia/patologia , Isquemia/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Recuperação de Função Fisiológica , Reperfusão , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: To develop models for prevalence estimation of peripheral arterial disease (PAD) and to validate them in an external cohort. METHODS: Model training cohort was a population based cross-sectional survey. Age, sex, smoking status, body mass index, total cholesterol (TC), high density lipoprotein (HDL), TC/HDL ratio, low density lipoprotein, fasting glucose, diabetes, hypertension, pulse pressure, and stroke history were considered candidate predicting variables. Ankle brachial index ≤ 0.9 was defined as the presence of peripheral arterial disease. Logistic regression method was used to build the prediction models. The likelihood ratio test was applied to select predicting variables. The bootstrap method was used for model internal validation. Model performance was validated in an external cohort. RESULTS: The final models included age, sex, pulse pressure, TC/HDL ratio, smoking status, diabetes, and stroke history. Area under receiver operating characteristics (AUC) with 95% confidence interval (CI) of the final model from the training cohort was 0.74 (0.70, 0.77). Model validation in another cohort revealed AUC (95% CI) of 0.72 (0.70, 0.73). P value of Hosmer-Lemeshow's model goodness of fit test was 0.75 indicating good model calibration. CONCLUSIONS: The developed model yielded a moderate usefulness for predicting the prevalence of PAD in general population.
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Modelos Teóricos , Doença Arterial Periférica/epidemiologia , Fatores Etários , Idoso , Índice Tornozelo-Braço , Área Sob a Curva , Biomarcadores/sangue , China/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Funções Verossimilhança , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Valor Preditivo dos Testes , Prevalência , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
Lumbar sympathetic blocks (LSBs) have long been used for the treatment of chronic lower extremity pain and for conditions such as complex regional pain syndrome (CRPS). With a better understanding of the autonomic nervous system and its function, these blocks have grown in their utility. Through this growth, however, our understanding of sympathetic-mediated pain is still vaguely understood. Here, we present a case of a patient who underwent a point-of-care ultrasound (POCUS) before and after an LSB, and we were able to show significant dilation of the posterior tibial artery (PTA) following the block. We propose that this arterial dilation plays a mechanistic role in providing pain relief to patients who undergo LSB. This increased blood flow can not only enhance healing properties to surrounding tissues but also allow for nitric oxide to play potential regulatory roles in pain pathways. Here, we also review potential mechanisms of the amelioration of sympathetic-mediated pain as well as the potential utilization of LSBs and neuromodulation in treating visceral pathologies through a better understanding of visceral somatic relationships.