RESUMO
OBJECTIVE: The aim of this study was to evaluate the use of clopidogrel at the time of carotid endarterectomy (CEA) and its association with postoperative complications. METHODS: Single-institution, retrospective review of a prospective database. RESULTS: From 2010 to 2017, CEA was performed in 1066 consecutive patients (median age, 73 years; 66% men). The indications for operation included ≥70% asymptomatic stenosis (458; 43%), prior stroke (314; 29%), and transient cerebral or retinal ischemia (294; 28%). At the time of operation, 509 (48%) patients were taking aspirin alone, 441 (41%) were taking clopidogrel (374 in combination with aspirin, 67 as sole therapy), 83 (8%) were on no documented antiplatelet medication, and 33 (3%) were taking warfarin (with therapeutic international normalized ratio). The likelihood of clopidogrel use at the time of operation was higher for patients with a history of symptomatic carotid disease (P = .002). Over the study period, clopidogrel use increased from 31.9% in 2010 to 56.8% in 2017, which corresponds to an 11% (95% confidence interval, 6%-15%) increase annually. Postoperative strokes occurred in 15 patients (overall incidence, 1.4%), the majority of which were minor (12/15; 80%). Six strokes occurred in patients taking aspirin alone (6/509; 1.2%), two in patients on clopidogrel and aspirin (2/441; 0.5%), two in patients taking clopidogrel alone (2/67; 2.9%), three in patients on no documented antiplatelet medication (3/83; 3.6%), and two in those taking warfarin (one of which was secondary to a fatal intracranial hemorrhage within 30 days of discharge [2/33; 6.1%]). The 30-day mortality rate was 0.03% (3/1066); the risk for the combined endpoint of any stroke, death, or myocardial infarction (MI) was 2.3% (25/1066), and the risk for major stroke, death, or MI was 1.2%. There was no apparent association between clopidogrel use and the incidence of postoperative bleeding (P = .59) or any other postoperative complication (stroke, death, MI, cranial nerve injury; P = .15). CONCLUSIONS: Clopidogrel use in our CEA practice has increased over time and has not been associated with an increased risk of postoperative complications, including bleeding. These data suggest that clopidogrel should not be discontinued prior to CEA and should be considered as part of 'optimal medical therapy' in patients undergoing CEA.
Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Infarto do Miocárdio , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , Clopidogrel/efeitos adversos , Endarterectomia das Carótidas/efeitos adversos , Ticlopidina/efeitos adversos , Varfarina/efeitos adversos , Fatores de Risco , Inibidores da Agregação Plaquetária/efeitos adversos , Aspirina/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Infarto do Miocárdio/etiologia , Resultado do Tratamento , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicaçõesRESUMO
PURPOSE: To report the safety and effectiveness outcomes through 2 years of the BioMimics 3D Vascular Stent System in the treatment of symptomatic patients with atherosclerotic femoropopliteal disease. MATERIALS AND METHODS: The tubular, nitinol BioMimics 3D stent, which was designed to impart a helical shape to the arterial segment, was implanted in 271 patients (mean age 68.4±9.5 years; 180 men) with de novo femoropopliteal lesions enrolled at 43 investigational sites [31 US (n=162), 6 German (n=78), and 6 Japanese (n=31)] in the prospective, single-arm MIMICS-2 investigational device exemption trial (ClinicalTrials.gov identifier NCT02400905) between June 2015 and October 2016. Mean lesion length was 81.2±38.4 mm, 30.0% of patients had total occlusions, and 45.9% had moderate to severe calcification. Primary safety and effectiveness endpoints were compared at 1 year with prespecified objective performance goals (OPGs) set by the VIVA Physicians organization. Outcomes through 2 years are reported. RESULTS: The primary effectiveness endpoint of 12-month primary stent patency was met by 182 of 249 patients (73.1%, 95% CI 67.3% to 78.2%), exceeding the OPG of 66%. The primary safety endpoint of 30-day freedom from major adverse events (MAEs) was met in 268 of 269 patients (99.6%, 95% CI 97.7% to 100%), exceeding the OPG of 88%. Kaplan-Meier estimates of freedom from loss of primary patency were 83.1% at 12 months and 70.2% at 24 months, freedom from MAEs estimates were 86.9% at 12 months and 79.2% at 24 months, and freedom from clinically-driven target lesion revascularization estimates were 88.0% at 12 months and 83.0% at 24 months. At 24 months, 88.2% of patients showed improvement of ≥1 Rutherford category; the ankle-brachial index was >0.9 for 64.4% vs 11.3% at baseline. There were no cases of stent fracture. CONCLUSION: Through 24 months, the BioMimics 3D Vascular Stent System provided safe and effective treatment for femoropopliteal lesions in patients with symptomatic peripheral artery disease.
Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Idoso , Procedimentos Endovasculares/efeitos adversos , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Artéria Poplítea/diagnóstico por imagem , Estudos Prospectivos , Desenho de Prótese , Stents , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, patients with PAD are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.
Assuntos
Doença Arterial Periférica , Anticolesterolemiantes , Doenças Cardiovasculares , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Lipídeos , Inibidores de PCSK9 , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Pró-Proteína Convertase 9RESUMO
BACKGROUND: The objective of this study was to compared outcomes of patients with aortoiliac occlusive disease (AIOD), limited to the common iliac artery, who underwent either aortoiliac thromboendarterectomy (AIE) or aortobiiliac bypass grafting (ABIB). METHODS: A single-center, retrospective analysis of consecutive patients with AIOD who underwent either AIE or ABIB between 2010 and 2019 from a prospective database. Patients with disease extending to the external iliac or common femoral arteries were excluded. Data collected included demographics, cardiovascular risk factors, indication for surgery, preoperative and postoperative ankle brachial indexes (ABIs), estimated blood loss, major adverse events (MAEs), and long-term patency. The study end point was clinical success, defined as improvement in ABIs with resolution of symptoms. MAEs included return to the operating room for any reason, postoperative myocardial infarction, stroke, pneumonia, or venous thromboembolism. RESULTS: Thirty-three patients, who met inclusion criteria, underwent repair for AIOD (AIE: 13; ABIB: 20) at our institution during this time. In both groups, there were more women than men (AIE: 11, ABIB: 10) with a mean age of 55 ± 7 years and 58 ± 6 years in the AIE and ABIB group, respectively. Indication for surgery included disabling claudication in 19 patients, ischemic rest pain in 13 patients, and tissue loss in one patient. No difference in cardiovascular risk factors or AIOD severity was noted between groups. Patients in the AIE group had slightly higher body mass index (30 ± 5 vs. 26 ± 6, P = 0.06). Two patients in each group required concomitant renal/mesenteric artery endarterectomy. One patient in the AIE group required bilateral femoral artery exposure and external iliac thrombectomy. MAEs (4 vs. 0) were higher in the ABIB group including, pneumonia in one patient, myocardial infarction in another, return to the operating room for evacuation of hematoma in the third and bypass graft thrombectomy with lower extremity angiography in the fourth patient. There were no differences in the intensive care unit or hospital length of stay between groups. Patients in both groups achieved return of normal ABI and complete resolution of their symptoms. At mean follow-up time of 43.4 ± 25.2 and 52.9 ± 35.4 months in the AIE and ABIB group, respectively, there was no symptomatic recurrence or need for reintervention while two patients in the ABIB group died of non-aortic-related issues. CONCLUSIONS: Both procedures were safe, effective, and conferred high long-term primary patency with no need for reintervention in patients with AIOD limited to the common iliac arteries.
Assuntos
Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular , Endarterectomia , Artéria Ilíaca/cirurgia , Adulto , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/fisiopatologia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Endarterectomia/efeitos adversos , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Tuberous sclerosis complex 2 (TSC2), or tuberin, is a pivotal regulator of the mechanistic target of rapamycin signaling pathway that controls cell survival, proliferation, growth, and migration. Loss of Tsc2 function manifests in organ-specific consequences, the mechanisms of which remain incompletely understood. Recent single cell analysis of the kidney has identified ATP-binding cassette G2 (Abcg2) expression in renal proximal tubules of adult mice as well as a in a novel cell population. The impact in adult kidney of Tsc2 knockdown in the Abcg2-expressing lineage has not been evaluated. We engineered an inducible system in which expression of truncated Tsc2, lacking exons 36-37 with an intact 3' region and polycystin 1, is driven by Abcg2. Here, we demonstrate that selective expression of Tsc2fl36-37 in the Abcg2pos lineage drives recombination in proximal tubule epithelial and rare perivascular mesenchymal cells, which results in progressive proximal tubule injury, impaired kidney function, formation of cystic lesions, and fibrosis in adult mice. These data illustrate the critical importance of Tsc2 function in the Abcg2-expressing proximal tubule epithelium and mesenchyme during the development of cystic lesions and remodeling of kidney parenchyma.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Fibrose/patologia , Doenças Renais Policísticas/patologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Linhagem da Célula , Feminino , Fibrose/genética , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Miofibroblastos/fisiologia , Doenças Renais Policísticas/metabolismo , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/farmacologia , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismoRESUMO
White adipocytes in adults are typically derived from tissue resident mesenchymal progenitors. The recent identification of de novo production of adipocytes from bone marrow progenitor-derived cells in mice challenges this paradigm and indicates an alternative lineage specification that adipocytes exist. We hypothesized that alternative lineage specification of white adipocytes is also present in human adipose tissue. Bone marrow from transgenic mice in which luciferase expression is governed by the adipocyte-restricted adiponectin gene promoter was adoptively transferred to wild-type recipient mice. Light emission was quantitated in recipients by in vivo imaging and direct enzyme assay. Adipocytes were also obtained from human recipients of hematopoietic stem cell transplantation. DNA was isolated, and microsatellite polymorphisms were exploited to quantify donor/recipient chimerism. Luciferase emission was detected from major fat depots of transplanted mice. No light emission was observed from intestines, liver, or lungs. Up to 35% of adipocytes in humans were generated from donor marrow cells in the absence of cell fusion. Nontransplanted mice and stromal-vascular fraction samples were used as negative and positive controls for the mouse and human experiments, respectively. This study provides evidence for a nontissue resident origin of an adipocyte subpopulation in both mice and humans.
Assuntos
Adipócitos Brancos/fisiologia , Tecido Adiposo/fisiologia , Células-Tronco/fisiologia , Animais , Células da Medula Óssea/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Fusão Celular/métodos , Linhagem da Célula/genética , Linhagem da Célula/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: Type II endoleak is the most commonly encountered endoleak after endovascular abdominal aortic aneurysm repair (EVAR). Some have advocated preoperative inferior mesenteric artery (IMA) embolization as a valid method for reducing the incidence of this endoleak, but controversies exist. We sought to demonstrate the impact of IMA embolization using a meta-analysis of currently available studies combined with our own experience. METHODS: We conducted an institutional review board-approved, retrospective analysis of all patients undergoing IMA embolization before EVAR between the years 2010 and 2015 and used as a control a similar group of patients with patent IMA. We divided patients from our own experience and 5 other studies into 2 groups: those who did not undergo IMA embolization (control) before EVAR and those who did. Rates of type II endoleaks, aneurysm sac regression, and secondary interventions were analyzed. RESULTS: A total of 620 patients from 6 studies were analyzed, including 258 patients who underwent an attempted IMA embolization before EVAR with a cumulative success rate of 99.2% (range, 93.8% to 100%). There was 1 fatality associated with IMA embolization. A meta-analysis showed that preoperative IMA embolization protected against type II endoleaks compared to the control group (odds ratio [OR], 0.31 [0.17-0.57]; P < 0.001, I2 = 43%). Furthermore, the rate of secondary intervention was significantly lower in the treatment group (OR, 0.12 [0.004-0.36]; P < 0.001, I2 = 0%). After IMA embolization, type II endoleak resulted from patent lumbar arteries in all 62 patients with persistent endoleak. CONCLUSIONS: Preoperative embolization of the IMA protects against the development of type II endoleaks and secondary interventions and may potentially lead to a rapid aneurysm sac regression. The procedure can be performed with a high technical success rate and minimal complications and should be considered in patients with IMA >3 mm before EVAR. A randomized trial, however, is required to clearly delineate the clinical significance of this technique.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Embolização Terapêutica/métodos , Endoleak/prevenção & controle , Procedimentos Endovasculares/efeitos adversos , Artéria Mesentérica Inferior , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Angiografia por Tomografia Computadorizada , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/mortalidade , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Artéria Mesentérica Inferior/diagnóstico por imagem , Minnesota , Razão de Chances , Retratamento , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Current recommendations suggest lifetime follow-up for endovascular aortic aneurysm repair (EVAR) patients to avoid consequences associated with endoleak and aneurysm enlargement. Follow-up compliance has been reported between 43% and 92%, with most single-center studies citing successful follow-up surveillance at less than 60%. We investigated follow-up completeness with a defined surveillance program and subsequent secondary intervention prevalence from a single center. METHODS: Our surveillance program notified patients of the need for follow-up imaging and surgeon review. Data were obtained from retrospective review of a prospective database, including operative and follow-up details, follow-up imaging completeness, endoleak incidence, and secondary intervention prevalence. RESULTS: Five hundred seventeen patients received elective EVAR from 2005 to 2015. Surveillance was achieved in 425 (82.3%). Mean number of follow-up studies was 4.2 ± 2.9 and median time to first follow-up was 36 days. Four hundred forty-eight patients (86.7%) had freedom from intervention. Sixty-nine unique patients (13.3%) had 107 secondary interventions. Median time to first secondary intervention in 69 patients was 476 days. Mean number of imaging studies for secondary intervention patients was 6.1 ± 3.9, compared with mean 3.4 ± 2.3 for patients without (P < 0.001). Overall mortality was 24.6% (n = 127), including 32 deaths of unknown cause (6.2% overall) and 95 of non-EVAR-related causes (18.3%). No aneurysm-related deaths were reported. CONCLUSIONS: Regular post-EVAR surveillance through a dedicated program resulted in a high rate of follow-up compliance, 13.3% rate of secondary intervention, and low aneurysm-related mortality. Careful lifetime surveillance remains important in long-term care following elective EVAR.
Assuntos
Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular , Diagnóstico por Imagem/métodos , Procedimentos Endovasculares , Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Diagnóstico por Imagem/normas , Intervalo Livre de Doença , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/terapia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Fidelidade a Diretrizes/normas , Humanos , Estimativa de Kaplan-Meier , Masculino , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Retratamento , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Thoracic aortic aneurysms can be found incidentally, however, patients can also present with acute dissection and or rupture that can be fatal. Symptoms that might indicate dissection include chest and back pain as well as lightheadedness. The diagnosis can be made with imaging studies such as computed tomography or magnetic resonance angiogram and sometimes transesophageal echocardiogram. Management is based on the aneurysmal size, location, extension, and the presence of complications. Although smaller localized and slow growing aneurysms can be monitored, larger and or complicated ones may warrant immediate repair. Less-common complications include compression over anatomic structures in the vicinity including vessels and the mediastinum. We report a unique case of a 71-year-old man who presented with a very large thoracic aortic aneurysm with dissection causing compression over the brachiocephalic veins and the mediastinum leading to facial and upper extremity swelling, dysphagia, and cough. This case represents a rare but significant complication of thoracic aortic aneurysm and emphasizes the challenges of its management.
Assuntos
Aneurisma da Aorta Torácica/complicações , Dissecção Aórtica/complicações , Veias Braquiocefálicas , Tosse/etiologia , Transtornos de Deglutição/etiologia , Edema/etiologia , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia/métodos , Veias Braquiocefálicas/diagnóstico por imagem , Veias Braquiocefálicas/fisiopatologia , Constrição Patológica , Tosse/diagnóstico , Transtornos de Deglutição/diagnóstico , Edema/diagnóstico , Face , Evolução Fatal , Hemodinâmica , Humanos , Angiografia por Ressonância Magnética , Masculino , Flebografia , Tomografia Computadorizada por Raios X , Extremidade SuperiorRESUMO
Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2(-/-) mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O(2), 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2(-/-) mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2(-/-) mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH.
Assuntos
Ventrículos do Coração/enzimologia , Hipertensão Pulmonar/etiologia , Hipertrofia Ventricular Direita/etiologia , Hipóxia/complicações , MAP Quinase Quinase Quinase 2/metabolismo , Miócitos Cardíacos/enzimologia , Remodelação Ventricular , Animais , Doença Crônica , Modelos Animais de Doenças , Regulação da Expressão Gênica , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertrofia Ventricular Direita/enzimologia , Hipertrofia Ventricular Direita/genética , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Hipóxia/enzimologia , Hipóxia/genética , Mediadores da Inflamação/metabolismo , MAP Quinase Quinase Quinase 2/deficiência , MAP Quinase Quinase Quinase 2/genética , Masculino , Camundongos , Camundongos Knockout , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Miócitos Cardíacos/patologia , Fosforilação , Fatores de Tempo , UltrassonografiaRESUMO
Hypoxia-induced pulmonary hypertension is characterized by progressive remodeling of the pulmonary artery (PA) system and loss of the transcription factor, cAMP response element binding protein (CREB) in PA smooth muscle cells (SMCs). Previous in vitro studies suggested that platelet-derived growth factor, a mitogen produced in the hypoxic arterial wall, elicits loss of CREB in medial SMCs via the PI3K/Akt pathway. These events trigger switching of SMCs from a quiescent, contractile phenotype to a proliferative, migratory, dedifferentiated, and synthetic phenotype, which contributes to PA thickening. Here, we investigated whether inhibition of PI3K or Akt could attenuate arterial remodeling in the lung and prevent CREB loss in PA medial SMCs in rats subjected to chronic hypoxia. Inhibition of either enzyme-blunted hypoxia-induced PA remodeling and SMC CREB depletion and diminished SMC proliferation and collagen deposition. Inhibition of Akt, but not PI3K, suppressed muscularization of distal arterioles and blunted right ventricular hypertrophy. Interestingly, mean PA pressure was elevated equally by hypoxia in untreated and inhibitor-treated groups but was normalized acutely by the Rho kinase inhibitor, Fasudil. We conclude that PI3K and Akt inhibitors can attenuate hypoxia-induced PA remodeling and SMC CREB depletion but fail to block the development of pulmonary hypertension because of their inability to repress Rho kinase-mediated vasoconstriction.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/agonistas , Hipertensão Pulmonar/prevenção & controle , Músculo Liso Vascular/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/metabolismo , Arteríolas/patologia , Proliferação de Células/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Inibidores Enzimáticos/uso terapêutico , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Hipertensão Pulmonar/etiologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/prevenção & controle , Hipóxia/fisiopatologia , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Estabilidade Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Circulação Pulmonar/efeitos dos fármacos , Ratos , Ratos Endogâmicos WKY , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Quinases Associadas a rho/metabolismoRESUMO
Congenital anomalies of the inferior vena cava (IVC) are rare and are estimated to be present in 0.07-8.7% of the general population. IVC agenesis (IVCA) is found in approximately 5% of cases of unprovoked lower extremity deep vein thrombosis in patients <30 years of age. Renal vein thrombosis (RVT) is an extremely rare and unusual presentation of IVCA. We report a unique case of a 23-year-old previously healthy man presenting with infrahepatic IVCA-induced bilateral RVT with azygos and hemiazygos continuation. To our knowledge, this is the third reported case in the literature of IVCA-induced RVT and the first to affect the bilateral renal veins in the absence of any other thrombogenic risk factors or any lower extremity venous complications. We also present a literature review of IVCA-induced vein thrombosis and highlight the lack of literature to manage this condition.
Assuntos
Veias Renais , Malformações Vasculares/complicações , Veia Cava Inferior/anormalidades , Trombose Venosa/etiologia , Anticoagulantes/uso terapêutico , Veia Ázigos/anormalidades , Humanos , Masculino , Flebografia/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Malformações Vasculares/diagnóstico , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Adulto JovemRESUMO
Takayasu arteritis is a rare, chronic form of large vessel vasculitis that characteristically involves the aorta and its branches. Its origin and disease process are currently unknown, although T lymphocytes and, most recently, B cells are thought to play a role. Common variable immunodeficiency (CVID) is a collection of heterogeneous disorders resulting in an antibody deficiency and recurrent infections, and is the most common symptomatic primary immunodeficiency disorder. This report presents a unique case of possible Takayasu arteritis with a history of CVID in a young man admitted with multiple cerebrovascular accidents. Takayasu arteritis may serve as the main cause of this presentation. The rarity of this case is further accentuated by the presence of moyamoya disease. Finally, the possible disease process and novel treatment of Takayasu arteritis is discussed briefly.
Assuntos
Imunodeficiência de Variável Comum/complicações , Doença de Moyamoya/complicações , Arterite de Takayasu/complicações , Adulto , Anticoagulantes/uso terapêutico , Biópsia , Angiografia Cerebral/métodos , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/tratamento farmacológico , Imunodeficiência de Variável Comum/imunologia , Humanos , Imunossupressores/uso terapêutico , Angiografia por Ressonância Magnética , Masculino , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/tratamento farmacológico , Doença de Moyamoya/imunologia , Imagem de Perfusão/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/etiologia , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/imunologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A subpopulation of adipocytes in the major adipose depots of mice is produced from hematopoietic stem cells rather than mesenchymal progenitors that are the source of conventional white and brown/beige adipocytes. To analyze the impact of hematopoietic stem cell-derived adipocytes (HSCDAs) in the adipose niche we transplanted HSCs in which expression of a diphtheria toxin gene was under the control of the adipocyte-specific adiponectin gene promoter into irradiated wild type recipients. Thus, only adipocytes produced from HSC would be ablated while conventional white and brown adipocytes produced from mesenchymal progenitor cells would be spared. Wild type mice transplanted with HSCs from mice containing a reporter gene, but not the diphtheria toxin gene, regulated by the adiponectin gene promoter served as controls. In mice in which HSCDA production was suppressed, adipocyte size declined while adipose depot weights were unchanged and the number of conventional adipocyte progenitors significantly increased. We also measured a paradoxical increase in circulating leptin levels while physical activity was significantly decreased in the HSCDA depleted mice. Finally, insulin sensitivity was significantly reduced in HSCDA depleted mice. In contrast, loss of HSCDA production had no effect on body weight, components of energy balance, or levels of several circulating adipokines and tissue-resident inflammatory cells. These data indicate that ablation of this low-abundance subpopulation of adipocytes is associated with changes in circulating leptin levels and leptin-regulated endpoints associated with adipose tissue function. How they do so remains a mystery, but our results highlight the need for additional studies to explore the role of HSCDAs in other physiologic contexts such as obesity, metabolic dysfunction or loss of sex hormone production.
Assuntos
Insulina , Leptina , Adipócitos/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Animais , Toxina Diftérica , Feminino , Células-Tronco Hematopoéticas , Insulina/metabolismo , Leptina/metabolismo , CamundongosRESUMO
Restenosis requiring treatment after carotid angioplasty/stenting is uncommon in clinical practice. Treatment options include repeat angioplasty (with or without another stent) or carotid endarterectomy. This report describes a patient with recurrent stenosis treated with eversion carotid endarterectomy and stent removal.
Assuntos
Angioplastia/instrumentação , Estenose das Carótidas/terapia , Endarterectomia das Carótidas/métodos , Stents , Estenose das Carótidas/diagnóstico , Remoção de Dispositivo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Live case demonstrations (LCDs) are now prevalent in medical education courses despite ethical concerns including that they may expose patients to undue risk. However, there are limited data regarding many aspects of LCDs to help inform policies and guidelines regarding them. METHODS: We conducted an Internet-based survey of clinicians who have served as faculty or attended the 2009 and 2010 professional meetings sponsored by VIVA (Vascular Interventional Advances). RESULTS: There were 106 VIVA 2009 respondents and 165 VIVA 2010 respondents. Observing an LCD was more valuable than watching a prerecorded video for most (70% in 2009; 82% in 2010) respondents. About one-third of respondents thought that LCD patients are exposed to more risk than non-LCD patients. Respondents who had been operators were more likely to agree that LCD patients are exposed to more risk (p = 0.001 in 2009; p = 0.022 in 2010). Approximately one-third of respondents in 2009 and one-half in 2010 thought that patients experience direct medical benefit in an LCD. The majority (71% in 2009; 76% in 2010) indicated that they would support the decision of a family member or friend to be an LCD patient, few (44% in 2009; 58% in 2010) indicated that they personally would agree to be an LCD patient. CONCLUSIONS: This survey provides new insights into the value and risk of LCDs. Obtaining the perspective of patients would be extremely valuable in helping to ensure that the ethical aspects of LCDs are addressed properly and thoroughly.
Assuntos
Atitude do Pessoal de Saúde , Educação Médica Continuada/ética , Ética Médica , Conhecimentos, Atitudes e Prática em Saúde , Segurança do Paciente , Gravação em Vídeo/ética , Congressos como Assunto , Educação Médica Continuada/métodos , Educação Médica Continuada/normas , Feminino , Humanos , Consentimento Livre e Esclarecido/ética , Internet , Masculino , Segurança do Paciente/normas , Guias de Prática Clínica como Assunto , Medição de Risco , Inquéritos e Questionários , Gravação em Vídeo/normasRESUMO
BACKGROUND: The number of cases involving patients undergoing vascular procedures who are prescribed clopidogrel or warfarin as treatment options continues to rise. Our aim was to examine outcomes related to antiplatelet or anticoagulation therapy in patients undergoing carotid endarterectomy (CEA). METHODS: A retrospective review of 260 consecutive patients undergoing CEA. Data including patient demographics, operative details, perioperative use of aspirin (ASA), clopidogrel, or warfarin, and early and/or late outcome(s) were collected. Endpoints included postoperative morbidity and/or mortality rate(s) and bleeding complications. RESULTS: The study included 152 men and 108 women (mean age = 69.3 years), with a mean follow-up of 406 days. In all, 46% of endarterectomies were for a symptomatic disease. The technique of eversion endarterectomy was applied in 126 (48.5%), Dacron-patch in 112 (43.1%), and bovine pericardial-patch in 14 (5.4%) of the cases. Among the patients, 171 were taking ASA, 50 were taking clopidogrel ± ASA, and 10 were taking warfarin (mean INR = 1.62; range, 1.2-2.1); the remaining 29 were not on any antiplatelet therapy. All patients who were on warfarin therapy underwent an eversion endarterectomy. Overall, there were 19 (7.3%) complications (12 major and seven minor). The 30-day stroke rate and stroke death rate was 0.7% and 1.1%, respectively. Patients taking clopidogrel developed more number of neck hematomas (16% vs. 1.7%, p = 0.0004) compared with patients who were on ASA alone. For patients taking clopidogrel, Dacron-patch repair resulted in more hematomas than eversion endarterectomy (35% vs. 4.2%, p = 0.012). There was no difference in the incidence of neck hematoma on the basis of endarterectomy technique in patients who were on ASA alone. The patients taking warfarin neither had a perioperative complication nor developed a neck hematoma. CONCLUSIONS: In this study, clopidogrel use during CEA resulted in a significant risk for developing a neck hematoma, particularly when using a Dacron-patch. The risk of a neck hematoma in patients who were on clopidogrel was much less when an eversion endarterectomy was performed.
Assuntos
Anticoagulantes/uso terapêutico , Endarterectomia das Carótidas , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/uso terapêutico , Distribuição de Qui-Quadrado , Clopidogrel , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Hematoma/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Infarto do Miocárdio/etiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Varfarina/uso terapêuticoRESUMO
Some adipocytes are produced from bone marrow hematopoietic stem cells. In vitro studies previously indicated that these bone marrow-derived adipocytes (BMDAs) were generated from adipose tissue macrophage (ATM) that lose their hematopoietic markers and acquire mesenchymal markers prior to terminal adipogenic differentiation. Here we interrogated whether this hematopoietic-to-mesenchymal transition drives BMDA production In vitro. We generated transgenic mice in which the lysozyme gene promoter (LysM) indelibly labeled ATM with green fluorescent protein (GFP). We discovered that adipose stroma contained a population of LysM-positive myeloid cells that simultaneously expressed hematopoietic/myeloid markers (CD45 and CD11b), and mesenchymal markers (CD29, PDGFRa and Sca-1) typically found on conventional adipocyte progenitors. These cells were capable of adipogenic differentiation In vitro and In vitro, while other stromal populations deficient in PDGFRa and Sca-1 were non-adipogenic. BMDAs and conventional adipocytes expressed common fat cell markers but exhibited little or no expression of hematopoietic and mesenchymal progenitor cell markers. The data indicate that BMDAs are produced from ATM simultaneously expressing hematopoietic and mesenchymal markers rather than via a stepwise hematopoietic-to-mesenchymal transition. Because BMDA production is stimulated by high fat feeding, their production from hematopoietic progenitors may maintain adipocyte production when conventional adipocyte precursors are diminished.
Assuntos
Adipócitos , Células da Medula Óssea , Tecido Adiposo , Animais , Diferenciação Celular , Células-Tronco Hematopoéticas , CamundongosRESUMO
BACKGROUND: The transcription factor CREB is diminished in smooth muscle cells (SMCs) in remodeled, hypertensive pulmonary arteries (PAs) in animals exposed to chronic hypoxia. Forced depletion of cyclic adenosine monophosphate response element binding protein (CREB) in PA SMCs stimulates their proliferation and migration in vitro. Platelet-derived growth factor (PDGF) produced in the hypoxic PA wall promotes CREB proteasomal degradation in SMCs via phosphatidylinositol-3-kinase/Akt signaling, which promotes phosphorylation of CREB at 2 casein kinase 2 (CK2) sites. Here we tested whether thiazolidinediones, agents that inhibit hypoxia-induced PA remodeling, attenuate SMC CREB loss. METHODS: Depletion of CREB and changes in casein kinase 2 catalytic subunit expression and activity were measured in PA SMC treated with PDGF. PA remodeling and changes in medial PA CREB and casein kinase 2 levels were evaluated in lung sections from rats exposed to hypoxia for 21 days. RESULTS: We found that the thiazolidinedione rosiglitazone prevented PA remodeling and SMC CREB loss in rats exposed to chronic hypoxia. Likewise, the thiazolidinedione troglitazone blocked PA SMC proliferation and CREB depletion induced by PDGF in vitro. Thiazolidinediones did not repress Akt activation by hypoxia in vivo or by PDGF in vitro. However, PDGF-induced CK2 alpha' catalytic subunit expression and activity in PA SMCs, and depletion of CK2 alpha' subunit prevented PDGF-stimulated CREB loss. Troglitazone inhibited PDGF-induced CK2 alpha' subunit expression in vitro and rosiglitazone blocked induction of CK2 catalytic subunit expression by hypoxia in PA SMCs in vivo. CONCLUSION: We conclude that thiazolidinediones prevent PA remodeling in part by suppressing upregulation of CK2 and loss of CREB in PA SMCs.