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1.
J Neuroinflammation ; 20(1): 9, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639663

RESUMO

Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR+ autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR+ MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects.


Assuntos
Interleucina-23 , Miastenia Gravis Autoimune Experimental , Camundongos , Humanos , Animais , Subunidade p19 da Interleucina-23 , Receptores Colinérgicos , Junção Neuromuscular/patologia , Autoanticorpos
2.
Clin Lung Cancer ; 24(1): 1-10, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36180314

RESUMO

INTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Receptores ErbB/genética , Biomarcadores , Mutação/genética , Estadiamento de Neoplasias
4.
Ann Thorac Surg ; 112(6): 1870-1876, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33333085

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has decreased surgical activity, particularly in the field of oncology, because of the suspicion of a higher risk of COVID-19-related severe events. This study aimed to investigate the feasibility and safety of thoracic cancer surgery in the most severely affected European and Canadian regions during the COVID-19 pandemic. METHODS: The study investigators prospectively collected data on surgical procedures for malignant thoracic diseases from January 1 to April 30, 2020. The study included patients from 6 high-volume thoracic surgery departments: Nancy and Strasbourg (France), Freiburg (Germany), Milan and Turin (Italy), and Montreal (Canada). The centers involved in this research are all located in the most severely affected regions of those countries. An assessment of COVID-19-related symptoms, polymerase chain reaction (PCR)-confirmed COVID-19 infection, rates of hospital and intensive care unit admissions, and death was performed for each patient. Every deceased patient was tested for COVID-19 by PCR. RESULTS: In the study period, 731 patients who underwent 734 surgical procedures were included. In the whole cohort, 9 cases (1.2%) of COVID-19 were confirmed by PCR, including 5 in-hospital contaminants. Four patients (0.5%) needed readmission for oxygen requirements. In this subgroup, 2 patients (0.3%) needed intensive care unit and mechanical ventilatory support. The total number of deaths in the whole cohort was 22 (3%). A single death was related to COVID-19 (0.14%). CONCLUSIONS: Maintaining surgical oncologic activity in the era of the COVID-19 pandemic seems safe and feasible, with very low postoperative morbidity or mortality. To continue to offer the best care to patients who do not have COVID-19, reports on other diseases are urgently needed.


Assuntos
COVID-19 , Neoplasias Torácicas/cirurgia , Procedimentos Cirúrgicos Torácicos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Torácicos/efeitos adversos
5.
Transplant Proc ; 51(10): 3375-3384, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31733791

RESUMO

OBJECTIVE: To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. MATERIAL AND METHODS: Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. RESULTS: DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. CONCLUSIONS: Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.


Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Transplante de Pulmão/mortalidade , Complicações Pós-Operatórias/sangue , Adulto , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco
6.
Chest ; 155(4): e91-e96, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30955586

RESUMO

A nonsmoker man in his 40s underwent bilateral lung transplantation with a referral diagnosis of genetic-related idiopathic pulmonary fibrosis (IPF). The patient had no medical history in childhood and early adulthood, nor was there a family history of IPF. His nonsmoker father presented with lung cancer at 59 years of age. The patient was a professional brass instrument player; he had started playing at 9 years of age, and he was recently playing 3 to 4 h per day. He had a 7-year clinical history of chronic cough and shortness of breath. Bilateral fine crackles were present at clinical examination. There was no digital clubbing. Data had been collected since 2015: no clinical or immunologic signs of connective tissue disease were evident, including autoantibodies for myositis or anti-synthetase syndrome. Chest radiograph showed diffuse interstitial lung disease. Results of pulmonary function tests yielded a restrictive pattern with decreased FVC and decreased total lung capacity (69% and 47% of predicted, respectively). The FEV1/FVC ratio was 86%, and carbon monoxide transfer coefficient was 36% of predicted. BAL cellular analysis consisted of macrophages (66%), lymphocytes (19%; CD4+/CD8+ ratio, 0.16), neutrophils (10%), and eosinophils (5%).


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , DNA/genética , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/diagnóstico por imagem , Mutação , não Fumantes , Proteína C Associada a Surfactante Pulmonar/genética , Adulto , Alveolite Alérgica Extrínseca/etiologia , Biópsia , Análise Mutacional de DNA , Diagnóstico Diferencial , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/genética , Masculino , Proteína C Associada a Surfactante Pulmonar/metabolismo , Radiografia Torácica , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
7.
Ann Thorac Surg ; 108(3): e195-e198, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30825451

RESUMO

We report an unusual case of a 53-year-old woman who presented with multiple lung cystic lesions presumed to be related to pulmonary hydatidosis, treated and followed for 3 years before surgical removal was decided. Unexpectedly, pathologic findings showed benign spindle cell proliferation. Immunohistochemical staining confirmed the smooth-muscle nature of the spindle cells, which were also positive for hormonal receptors and corresponded to multiple cystic pulmonary hamartomas.


Assuntos
Albendazol/uso terapêutico , Equinococose Pulmonar/diagnóstico por imagem , Hamartoma/patologia , Leiomioma/patologia , Leiomioma/cirurgia , Neoplasias Pulmonares/cirurgia , Biópsia por Agulha , Diagnóstico Diferencial , Progressão da Doença , Equinococose Pulmonar/diagnóstico , Equinococose Pulmonar/cirurgia , Feminino , Hamartoma/diagnóstico , Humanos , Histerectomia/métodos , Imuno-Histoquímica , Leiomioma/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Pessoa de Meia-Idade , Pneumonectomia/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medição de Risco , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
8.
J Autoimmun ; 98: 59-73, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30578016

RESUMO

IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17 cell pathway in the thymic inflammatory and pathogenic events. We found that thymuses of MG patients displayed overexpression of Interleukin-17, signature cytokine of activated Th17 cells. This activation was sustained by a higher secretion of Interleukin-23 by TEC, in addition to the increased expression of cytokines involved in Th17 cell development. The overexpression of Interleukin-23 was due to a dysregulation of interferon type I pathway. Besides, Interleukin-17 secreted, and Th17 cells were localized around thymic ectopic germinal centers. These cells expressed podoplanin, a protein involved in B-cell maturation and antibody secretion. Finally, production of Interleukin-23 was also promoted by Interleukin-17 secreted itself by Th17 cells, highlighting a chronic loop of inflammation sustained by thymic cell interaction. Activation of the IL-23/Th17 pathway in the thymus of autoimmune myasthenia gravis patients creates an unstoppable loop of inflammation that may participate in ectopic germinal center maintenance. To alleviate the physio-pathological events in myasthenia gravis patients, this pathway may be considered as a new therapeutic target.


Assuntos
Inflamação/imunologia , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Miastenia Gravis/imunologia , Células Th17/imunologia , Timo/metabolismo , Adolescente , Adulto , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Transdução de Sinais , Timo/patologia , Adulto Jovem
9.
Clin Lung Cancer ; 19(6): e919-e931, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30217639

RESUMO

BACKGROUND: Emerging data highlight different clinical behaviors according to KRAS amino acid substitutions (AASs) in patients with non-small-cell lung cancer (NSCLC). We aimed to evaluate whether different KRAS AASs were associated with different responses to chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed data from 1190 patients with KRAS mutations who underwent first-line platinum-based chemotherapy for stage IV NSCLC. The response to different chemotherapy regimens was evaluated using the Response Evaluation Criteria In Solid Tumors criteria (v 1.1). Overall survival and time to progression (TTP) were secondary endpoints. RESULTS: Taxane was associated with the best response in the entire cohort (odds ratio, 2.52; 95% confidence interval [CI], 1.82-3.48; P < .001), especially in G12V patients (odds ratio, 2.15; 95% CI, 1.05-4.41; P = .036). Taxane was associated with improved TTP in the entire cohort (hazard ratio [HR], 0.31; 95% CI, 0.26-0.38; P < .001), especially in G13D patients (HR, 0.47; 95% CI, 0.22-1.01; P = .054). Pemetrexed was associated with the worst TTP in the entire cohort, particularly in G12V patients, who had the worst response rates (HR, 0.55; 95% CI, 0.30-0.99; P = .049). No impact on overall survival was observed according to different chemotherapy regimens and AASs. CONCLUSION: KRAS-specific AAS appears to induce different responses to chemotherapy regimens after first-line platinum-based chemotherapy in advanced NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação/genética , Pemetrexede/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxoides/uso terapêutico , Idoso , Biomarcadores Farmacológicos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida
10.
Heart Lung ; 47(3): 248-249, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29506763

RESUMO

BACKGROUND: Adequate strategies using either transthoracic (TTE) or transesophageal (TEE) echocardiography in patients receiving cardiopulmonary resuscitation (CPR) is an ongoing area of research. OBJECTIVES: As transthoracic point-of-care ultrasound (POCUS) during cardiac arrest resuscitation might result in an increased duration of interruptions in the delivery of chest compressions; the use of TEE has been proposed as an alternative. METHODS: No technical complications of either TTE nor TEE are so far being reported in the literature. RESULTS: We report the case of a left intramural atrial hematoma complicating TEE procedure during cardiac arrest. This highlights a unique and to our knowledge, first-in-man, described complicating TEE procedure during CPR. CONCLUSIONS: Further research on the safety of transesophageal echo during CRP is mandatory and the question about any potential harm of particular interest.


Assuntos
Ecocardiografia Transesofagiana , Parada Cardíaca/complicações , Átrios do Coração/lesões , Hematoma/complicações , Reanimação Cardiopulmonar , Humanos
11.
Eur J Cardiothorac Surg ; 53(6): 1173-1179, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29377988

RESUMO

OBJECTIVES: As the adoption of robotic procedures becomes more widespread, additional risk related to the learning curve can be expected. This article reports the results of a Delphi process to define procedures to optimize robotic training of thoracic surgeons and to promote safe performance of established robotic interventions as, for example, lung cancer and thymoma surgery. METHODS: In June 2016, a working panel was spontaneously created by members of the European Society of Thoracic Surgeons (ESTS) and European Association for Cardio-Thoracic Surgery (EACTS) with a specialist interest in robotic thoracic surgery and/or surgical training. An e-consensus-finding exercise using the Delphi methodology was applied requiring 80% agreement to reach consensus on each question. Repeated iterations of anonymous voting continued over 3 rounds. RESULTS: Agreement was reached on many points: a standardized robotic training curriculum for robotic thoracic surgery should be divided into clearly defined sections as a staged learning pathway; the basic robotic curriculum should include a baseline evaluation, an e-learning module, a simulation-based training (including virtual reality simulation, Dry lab and Wet lab) and a robotic theatre (bedside) observation. Advanced robotic training should include e-learning on index procedures (right upper lobe) with video demonstration, access to video library of robotic procedures, simulation training, modular console training to index procedure, transition to full-procedure training with a proctor and final evaluation of the submitted video to certified independent examiners. CONCLUSIONS: Agreement was reached on a large number of questions to optimize and standardize training and education of thoracic surgeons in robotic activity. The production of the content of the learning material is ongoing.


Assuntos
Educação de Pós-Graduação em Medicina/métodos , Procedimentos Cirúrgicos Robóticos/educação , Cirurgiões/educação , Cirurgia Torácica/organização & administração , Procedimentos Cirúrgicos Torácicos/educação , Competência Clínica , Consenso , Currículo , Humanos , Curva de Aprendizado , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgiões/organização & administração , Procedimentos Cirúrgicos Torácicos/métodos
12.
Ann Surg Oncol ; 25(4): 1069-1078, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29362963

RESUMO

BACKGROUND: The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. OBJECTIVE: We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. METHODS: We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. RESULTS: EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027-0.999; p = 0.05). CONCLUSION: The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Éxons , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
14.
Ann Thorac Surg ; 104(4): 1194-1199, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28760464

RESUMO

BACKGROUND: Minimally invasive surgery, stereotactic radiotherapy, and radiofrequency ablation are commonly proposed in the case of pulmonary colorectal-metastasis as alternatives to conventional open surgery. Preoperative imaging assessment by computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (FDG-PET) are critical to guide oncologic radical treatment. Our aim was to investigate the accuracy of CT and FDG-PET for the evaluation of the number of pulmonary colorectal metastases and thoracic lymph nodal involvement (LNI). METHODS: Patients who underwent lung surgical resection for pulmonary colorectal metastases from 2004 to 2014 were analyzed. Concordance between histology, CT scan, and FDG-PET findings were assessed. RESULTS: Data of 521 patients were analyzed. Of those, FDG-PET was performed in 435 (83.5%). A moderate agreement between both CT scan (kappa index: 0.42) and FDG-PET (kappa index: 0.42) findings and the histologically proven number of metastases was observed. The number of histologically proven metastases was correctly discriminated in 61.7% of cases with CT scan and in 61.8% of cases with FDG-PET. Multiple metastases were discovered in 20.9% of clinical single metastasis cases with CT scan, and in 24.4% of those cases with FDG-PET. One hundred fifty patients (29.1%) presented with pathologic LNI. A poor agreement was observed between LNI and CT scan findings (kappa index: 0.02), and a weak agreement was observed concerning LNI and FDG-PET findings (kappa index: 0.39). CONCLUSIONS: Computed tomography and FDG-PET have limitations if the objective is to detect all malignant nodules and to discriminate the LNI in cases of pulmonary metastases of colorectal cancer.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Metástase Linfática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Erros de Diagnóstico , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Ann Thorac Surg ; 104(2): e207-e209, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28734456

RESUMO

Clamshell (bilateral anterolateral thoracotomy combined to transverse sternotomy) is an invasive surgical approach that is helpful in particular situations, especially bilateral lung transplantation. The closure technique remains challenging because clamshell incision can end with override, separation, or sternal pseudarthrosis complications. We describe the use of new absorbable sternal pins to stabilize the sternal closure and to help avoid additional sternal complications.


Assuntos
Implantes Absorvíveis , Pinos Ortopédicos , Transplante de Pulmão , Esternotomia/efeitos adversos , Deiscência da Ferida Operatória/cirurgia , Toracotomia/efeitos adversos , Técnicas de Fechamento de Ferimentos , Humanos , Esterno/cirurgia , Transplantados
16.
JCI Insight ; 2(7): e89665, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28405609

RESUMO

Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether and how in vitro-preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model by subcutaneously grafting thymic MG fragments into immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed human anti-AChR Abs in the serum, and 50% of the animals displayed MG-like symptoms that correlated with the loss of AChR at the muscle endplates. Interestingly, each mouse experiment recapitulated the MG features of each patient. We next demonstrated that cMSCs markedly improved MG, reducing the level of anti-AChR Abs in the serum and restoring AChR expression at the muscle endplate. Resting MSCs had a smaller effect. Finally, we showed that the underlying mechanisms involved (a) the inhibition of cell proliferation, (b) the inhibition of B cell-related and costimulatory molecules, and (c) the activation of the complement regulator DAF/CD55. In conclusion, this study shows that a preconditioning step promotes the therapeutic effects of MSCs via combined mechanisms, making cMSCs a promising strategy for treating MG and potentially other autoimmune diseases.


Assuntos
Linfócitos B/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Miastenia Gravis Autoimune Experimental/terapia , Receptores Colinérgicos/imunologia , Adolescente , Adulto , Animais , Anticorpos Monoclonais/sangue , Criança , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Adulto Jovem
17.
Eur J Cardiothorac Surg ; 51(2): 255-262, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28186237

RESUMO

OBJECTIVES: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status. METHODS: We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known. RESULTS: A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58­98.42) vs 24 months (1.15­46.86), P = 0.001] and OS [101 vs 55 months (49.77­60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97­118.02) vs 60 months (53­66.99), P < 0.001; median LRRFS: 76 months (64.62­87.38) vs 44 months (35.27­52.73), P < 0.001]. CONCLUSION: Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.


Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Antineoplásicos/administração & dosagem , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Masculino , Metastasectomia , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
18.
Circ J ; 81(5): 660-667, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28202855

RESUMO

BACKGROUND: Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. CONCLUSIONS: Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.


Assuntos
Arritmias Cardíacas/etiologia , Transplante de Pulmão/efeitos adversos , Adolescente , Adulto , Idoso , Arritmias Cardíacas/mortalidade , Fibrilação Atrial , Flutter Atrial , Criança , Humanos , Incidência , Transplante de Pulmão/mortalidade , Pessoa de Meia-Idade , Mortalidade , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco
19.
Ann Thorac Surg ; 103(3): 881-889, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28168966

RESUMO

BACKGROUND: Postpneumonectomy acute respiratory distress syndrome (ppARDS) is a life-threatening condition with a disastrous prognosis. This study assessed the efficacy of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with unresponsive severe ppARDS. METHODS: We retrospectively reviewed data of all patients treated with VV-ECMO for ppARDS from January 2009 to December 2015. We calculated the Sequential Organ Failure Assessment score before ECMO insertion and monitored the subsequent mechanical ventilation settings. The primary end point was hospital survival. The secondary end point was the ability to achieve a protective ventilatory strategy allowing lung recovery on ECMO. RESULTS: VV-ECMO was indicated in 8 ppARDS patients for refractory hypoxemia (median partial pressure of arterial oxygen/fraction of inspired oxygen: 68 [range, 60 to 75] mm Hg). Median Sequential Organ Failure Assessment before ECMO was 15 (range, 12 to 17), predicting a mortality rate greater than 80%. Median duration of ECMO was 9.5 (range, 5 to 16) days. Tidal volumes and plateau pressures both decreased on ECMO (pre-ECMO tidal volume: 412 [range, 250 to 450 mL] vs ECMO tidal volume: 277 [range, 105 to 367 mL], p = 0.0156; pre-ECMO plateau pressure: 34 [range, 32 to 40] cm H2O vs ECMO plateau pressure: 24.5 [range, 23.3 to 27.3] cm H2O, p = 0.0195). ECMO could be weaned in 7 patients (87.5%). Hospital survival was 50%. CONCLUSIONS: Hospital survival was better than predicted before ECMO insertion. In severe and refractory ppARDS, VV-ECMO allows lung recovery and therefore increased survival.


Assuntos
Oxigenação por Membrana Extracorpórea , Pneumonectomia/efeitos adversos , Síndrome do Desconforto Respiratório/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Respiração Artificial , Estudos Retrospectivos
20.
Surg Endosc ; 31(3): 1250-1256, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27405483

RESUMO

BACKGROUND: Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated. METHODS: We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the χ 2 test and Student's t test; any p value ≤0.05 was considered as significant. RESULTS: Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p < 0.001), history of cancer (p < 0.001), history of stroke (p = 0.05), and the presence of pleural adhesions (p = 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate. CONCLUSIONS: We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context.


Assuntos
Pneumopatias/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Idoso , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade
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