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1.
J Neuroinflammation ; 18(1): 270, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789272

RESUMO

Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5' UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymus of myasthenia gravis (MG) patients, a prototypical autoimmune disease. We thus analyzed the number of CGG triplets in FMR1 in MG, and explored the regulatory mechanisms affecting thymic FMR1 expression. We measured the number of CGGs using thymic DNA from MG and controls, but no abnormalities in CGGs were found in MG that could explain thymic decrease of FMR1. We next analyzed by RT-PCR the expression of FMR1 and its transcription factors in thymic samples, and in thymic epithelial cell cultures in response to inflammatory stimuli. In control thymuses, FMR1 expression was higher in males than females, and correlated with CTCF (CCCTC-binding factor) expression. In MG thymuses, decreased expression of FMR1 was correlated with both CTCF and MAX (Myc-associated factor X) expression. Changes in FMR1 expression were supported by western blot analyses for FMRP. In addition, we demonstrated that FMR1, CTCF and MAX expression in thymic epithelial cells was also sensitive to inflammatory signals. Our results suggest that FMR1 could play a central role in the thymus and autoimmunity. First, in relation with the higher susceptibility of females to autoimmune diseases. Second, due to the modulation of its expression by inflammatory signals that are known to be altered in MG thymuses.


Assuntos
Proteína do X Frágil da Deficiência Intelectual/biossíntese , Miastenia Gravis/metabolismo , Timo/metabolismo , Adolescente , Adulto , Autoimunidade/genética , Fator de Ligação a CCCTC/biossíntese , Fator de Ligação a CCCTC/genética , Células Cultivadas , DNA/química , DNA/genética , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto Jovem
2.
J Card Surg ; 35(4): 912-915, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32092176

RESUMO

BACKGROUND AND AIM: Over the past years, three-dimensional (3D) models of patient-specific anatomical conditions are being used to improve the comprehension and surgical management of a variety of diseases. It is an additional diagnostic tool that aids clinical decision-making. Furthermore, this technology is still not routinely used in the medical field since its availability is limited by cost and complex process. METHODS AND RESULTS: We describe a patient with a balanced-type double aortic arch encircling trachea and esophagus. Considering the clinical symptoms, surgical decompression of these structures and defined aortic arch reconstruction was indicated. The 3D printed model revealed narrowing of the left aortic arch at the junction of the descending thoracic aorta that did not clearly appear on the conventional images reconstruction. The left aortic arch was divided and the symptoms completely disappeared. No immediate or late complications occurred. CONCLUSION: 3D printed models can be helpful in surgical planning of congenital heart malformations. It should be strongly considered as an additional tool in complex cases.


Assuntos
Aorta Torácica/anormalidades , Aorta Torácica/cirurgia , Modelos Anatômicos , Planejamento de Assistência ao Paciente , Impressão Tridimensional , Tomada de Decisões , Descompressão Cirúrgica/métodos , Esôfago/irrigação sanguínea , Humanos , Lactente , Masculino , Procedimentos de Cirurgia Plástica/métodos , Traqueia/irrigação sanguínea , Anel Vascular/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos
3.
J Surg Oncol ; 117(7): 1570-1574, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29573419

RESUMO

BACKGROUND: Traditionally, treatment for stage IIIB (T4N2M0 and T1-4N3M0) NSCLC consists in definitive chemoradiation. Surgery is used only anecdotally. Here, we studied outcome for patients treated with multimodality including surgery. METHODS: Patients who underwent surgery for stage IIIB between 2000 and 2015 were retrospectively reviewed and data analyzed. Patients were selected for surgery if they would tolerate multimodality treatment, the tumor was deemed upfront resectable, and N2-N3 involvement was limited to a non-bulky single site. Survival was calculated from the date of surgery until last follow-up. Univariate and multivariate analysis were performed to identify prognostic factors. RESULTS: During the study period, 5416 patients underwent resection for NSCLC in our center. Sixty patients (1%) had clinical stage IIIB. Thirty-two patients had T4N2 NSCLC involving the carina and/or superior vena cava (n = 25, 78%), left atrium (n = 5, 16%), or other (n = 2, 6%). Half of the 28 patients with N3-disease had supraclavicular node involvement. Pneumonectomy was performed in 27 patients (45%). Twenty-nine patients (48%) had induction therapy, with chemotherapy alone. Adjuvant therapy was administered to 52 patients (87%), mostly chemoradiation. Complete resection rate was 92%. Post-operative mortality was 3%. Three- and 5-year overall survivals were 51% and 39%, respectively. Multivariate analysis identified incomplete resection (P = 0.008) and absence of adjuvant treatment (P = 0.032) as poor survival prognostic factors. CONCLUSIONS: Surgery can be considered as a component of multimodality therapy in highly selected patients with stage IIIB NSCLC based on encouraging 5-year survival of 39%.


Assuntos
Adenocarcinoma/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/mortalidade , Pneumonectomia/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
4.
Anaerobe ; 32: 32-33, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25448620

RESUMO

Post-sternotomy mediastinitis, a nosocomial infection mostly caused by staphylococci, can be life-threatening. A case of mediastinitis due to Finegoldia magna after a coronary artery bypass graft surgery was reviewed. Although this bacterium is difficult to be isolated from routine blood cultures, a F. magna bacteriemia associated with mediastinitis was diagnosed.


Assuntos
Firmicutes , Infecções por Bactérias Gram-Positivas/microbiologia , Mediastinite/microbiologia , Complicações Pós-Operatórias , Esternotomia , Idoso , Infecção Hospitalar , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Masculino , Mediastinite/diagnóstico , Mediastinite/tratamento farmacológico , Resultado do Tratamento
5.
Rev Esp Cardiol (Engl Ed) ; 76(1): 10-18, 2023 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35570123

RESUMO

INTRODUCTION AND OBJECTIVES: Diagnosis, management, and surgical decision-making in children and adults with congenital heart disease are largely based on echocardiography findings. A recent development in cardiac imaging is fusion of different imaging modalities. Our objective was to evaluate the feasibility of computed tomography (CT) and 3-dimensional (3D) transthoracic echocardiography (TTE) fusion in children and adults with congenital heart disease. METHODS: We prospectively included 14 patients, 13 of whom had congenital heart disease, and who underwent both CT and 3D TTE as part of their usual follow-up. We described the steps required to complete the fusion process (alignment, landmarks, and superimposition), navigation, and image evaluation. RESULTS: Median age was 9.5 [2.7-15.7] years, 57% were male, and median body surface area was 0.9 m2 [0.6-1.7]. Congenital heart disease was classified as simple (n=4, 29%), moderate (n=4, 29%), or complex (n=6, 42%). 3D TTE-CT fusion was successful in all patients. Median total time to complete the fusion process was 735 [628-1163] seconds, with no significant difference according to the degree of complexity of the defects. Landmarks were significantly modified in complex congenital heart disease. CONCLUSIONS: We established the feasibility and accuracy of 3D TTE-CT fusion in a population of children and adults with a variety of congenital heart diseases. The simultaneous visualization of many intracardiac structures may help to understand the anatomical features of congenital heart disease without limitations regarding age, weight, or complexity of the congenital defects.


Assuntos
Ecocardiografia Tridimensional , Cardiopatias Congênitas , Criança , Adulto , Humanos , Masculino , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Ecocardiografia/métodos , Coração/diagnóstico por imagem , Ecocardiografia Tridimensional/métodos , Tomografia Computadorizada por Raios X
6.
Pulm Circ ; 12(1): e12017, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35506099

RESUMO

A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week-0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two- to three-fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points, r² = 0.95); (2) in the subgroup studied at W16 (n = 21, r² = 0.97); and (3) when all data were pooled (n = 91, r² = 0.97, sPAP range 9-112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species- and/or model-dependent and thus must be validated.

7.
J Thorac Cardiovasc Surg ; 157(2): 655-666.e7, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30669226

RESUMO

BACKGROUND: Right ventricular (RV) failure is the main prognostic factor in pulmonary hypertension, and ventricular capillary density (CD) has been reported to be a marker of RV maladaptive remodeling and failure. Our aim was to determine whether right intracoronary endothelial progenitor cell (EPC) infusion can improve RV function and CD in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: We compared 3 groups: sham (n = 5), CTEPH (n = 6), and CTEPH with EPC infusion (CTEPH+EPC; n = 5). After EPC isolation from CTEPH+EPC piglet peripheral blood samples at 3 weeks, the CTEPH and sham groups underwent right intracoronary infusion of saline, and the CTEPH+EPC group received EPCs at 6 weeks. RV function, pulmonary hemodynamics, and myocardial morphometry were investigated in the animals at 10 weeks. RESULTS: After EPC administration, the RV fractional area change increased from 32.75% (interquartile range [IQR], 29.5%-36.5%) to 39% (IQR, 37.25%-46.50%; P = .030). The CTEPH+EPC piglets had reduced cardiomyocyte surface areas (from 298.3 µm2 [IQR, 277.4-335.3 µm2] to 234.6 µm2 (IQR, 211.1-264.7 µm2; P = .017), and increased CD31 expression (from 3.12 [IQR, 1.27-5.09] to 7.14 [IQR, 5.56-8.41; P = .017). EPCs were found in the RV free wall at 4 and 24 hours after injection but not 4 weeks later. CONCLUSIONS: Intracoronary infusion of EPC improved RV function and CD in a piglet model of CTEPH. This novel cell-based therapy might represent a promising RV-targeted treatment in patients with pulmonary hypertension.


Assuntos
Células Progenitoras Endoteliais/transplante , Neovascularização Fisiológica , Hipertensão Arterial Pulmonar/cirurgia , Embolia Pulmonar/complicações , Transplante de Células-Tronco , Disfunção Ventricular Direita/prevenção & controle , Função Ventricular Direita , Remodelação Ventricular , Animais , Animais Recém-Nascidos , Pressão Arterial , Células Cultivadas , Modelos Animais de Doenças , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Embolia Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Sus scrofa , Fatores de Tempo , Transplante Autólogo , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
8.
Pulm Circ ; 8(2): 2045893218755979, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29480154

RESUMO

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by an increase in pulmonary arterial pressure due to pathological changes to the pulmonary vascular bed. As a result, the right ventricle (RV) is subject to an increased afterload and undergoes multiple changes, including a decrease in capillary density. All of these dysfunctions lead to RV failure. A number of studies have shown that RV function is one of the main prognostic factors for PAH patients. Many stem cell therapies targeting the left ventricle are currently undergoing development. The promising results observed in animal models have led to clinical trials that have shown an improvement of cardiac function. In contrast to left heart disease, stem cell therapy applied to the RV has remained poorly studied, even though it too may provide a therapeutic benefit. In this review, we discuss stem cell therapy as a treatment for RV failure in PAH. We provide an overview of the results of preclinical and clinical studies for RV cell therapies. Although a large number of studies have targeted the pulmonary circulation rather than the RV directly, there are nonetheless encouraging results in the literature that indicate that cell therapies may have a direct beneficial effect on RV function. This cell therapy strategy may therefore hold great promise and warrants further studies in PAH patients.

9.
Ann Thorac Surg ; 106(1): 207-213, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29551629

RESUMO

BACKGROUND: Radiotherapy has long been the treatment of choice for local control of Ewing sarcoma of the chest wall (ESCW). However, there is debate regarding the use of surgery versus radiotherapy. The objective of this study was to identify risk factors that may affect long-term outcomes of nonmetastatic ESCW treated with preoperative chemotherapy (CT) followed by en bloc resection and adjuvant CT or chemoradiation. METHODS: Between 1996 and 2014, 30 patients with a median age of 25 years (SD ± 8.9 years) were treated at Marie-Lannelongue Hospital in Le Plessis-Robinson, France. Adjuvant therapy was used in 27 patients: CT for 6, chemoradiation for 20, and radiotherapy for 1. Patients' demographics, treatment data, tumor features, and outcomes were collected. RESULTS: In this cohort of patients who received multimodal therapy, including neoadjuvant CT and en bloc resection, there was no postoperative mortality. Eight patients (27%) experienced postoperative complications. Resection included at least one rib (n = 27) and the sternum (n = 1) or the spine (n = 8). Negative and microscopic disease resections were achieved in 28 and 2 patients, respectively. Tumor viability (TV) was ≤5% in 18 patients (60%). In patients with TV >5% at definitive histologic examination, adjuvant chemoradiation was associated with a better long-term outcome than was treatment with adjuvant CT alone. The 5-year overall survival and disease-free survival rates were 60.7% and 41.0%, respectively, with a median survival of 87 months. By univariate analysis, TV >5% and pleural extension at diagnosis were associated with poorer long-term survival (p < 0.05). CONCLUSIONS: Multimodality treatment of ESCW, including neoadjuvant CT followed by en bloc resection and adjuvant CT or chemoradiation, is associated with excellent long-term outcomes.


Assuntos
Neoplasias Ósseas/cirurgia , Recidiva Local de Neoplasia/mortalidade , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Parede Torácica/cirurgia , Adulto , Fatores Etários , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteotomia/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/patologia , Fatores Sexuais , Análise de Sobrevida , Parede Torácica/patologia , Adulto Jovem
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