Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
J Neuroinflammation ; 20(1): 9, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639663

RESUMEN

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.


Asunto(s)
Interleucina-23 , Miastenia Gravis Autoinmune Experimental , Ratones , Humanos , Animales , Subunidad p19 de la Interleucina-23 , Receptores Colinérgicos , Unión Neuromuscular/patología , Autoanticuerpos
2.
Clin Lung Cancer ; 24(1): 1-10, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36180314

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Femenino , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Estudios Prospectivos , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Receptores ErbB/genética , Biomarcadores , Mutación/genética , Estadificación de Neoplasias
4.
Ann Thorac Surg ; 112(6): 1870-1876, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33333085

RESUMEN

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.


Asunto(s)
COVID-19 , Neoplasias Torácicas/cirugía , Procedimientos Quirúrgicos Torácicos , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Procedimientos Quirúrgicos Torácicos/efectos adversos
5.
Transplant Proc ; 51(10): 3375-3384, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31733791

RESUMEN

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.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus/sangre , Hemoglobina Glucada/análisis , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias/sangre , Adulto , Diabetes Mellitus/etiología , Diabetes Mellitus/mortalidad , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo
6.
Chest ; 155(4): e91-e96, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30955586

RESUMEN

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%).


Asunto(s)
Alveolitis Alérgica Extrínseca/diagnóstico , ADN/genética , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/diagnóstico por imagen , Mutación , No Fumadores , Proteína C Asociada a Surfactante Pulmonar/genética , Adulto , Alveolitis Alérgica Extrínseca/etiología , Biopsia , Análisis Mutacional de ADN , Diagnóstico Diferencial , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/genética , Masculino , Proteína C Asociada a Surfactante Pulmonar/metabolismo , Radiografía Torácica , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X
7.
Ann Thorac Surg ; 108(3): e195-e198, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30825451

RESUMEN

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.


Asunto(s)
Albendazol/uso terapéutico , Equinococosis Pulmonar/diagnóstico por imagen , Hamartoma/patología , Leiomioma/patología , Leiomioma/cirugía , Neoplasias Pulmonares/cirugía , Biopsia con Aguja , Diagnóstico Diferencial , Progresión de la Enfermedad , Equinococosis Pulmonar/diagnóstico , Equinococosis Pulmonar/cirugía , Femenino , Hamartoma/diagnóstico , Humanos , Histerectomía/métodos , Inmunohistoquímica , Leiomioma/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Persona de Mediana Edad , Neumonectomía/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Medición de Riesgo , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía
8.
J Autoimmun ; 98: 59-73, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30578016

RESUMEN

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.


Asunto(s)
Inflamación/inmunología , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Miastenia Gravis/inmunología , Células Th17/inmunología , Timo/metabolismo , Adolescente , Adulto , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Transducción de Señal , Timo/patología , Adulto Joven
9.
Clin Lung Cancer ; 19(6): e919-e931, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30217639

RESUMEN

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.


Asunto(s)
Antineoplásicos/uso terapéutico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación/genética , Pemetrexed/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Taxoides/uso terapéutico , Anciano , Biomarcadores Farmacológicos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Análisis de Supervivencia
10.
Heart Lung ; 47(3): 248-249, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29506763

RESUMEN

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.


Asunto(s)
Ecocardiografía Transesofágica , Paro Cardíaco/complicaciones , Atrios Cardíacos/lesiones , Hematoma/complicaciones , Reanimación Cardiopulmonar , Humanos
11.
Eur J Cardiothorac Surg ; 53(6): 1173-1179, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29377988

RESUMEN

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.


Asunto(s)
Educación de Postgrado en Medicina/métodos , Procedimientos Quirúrgicos Robotizados/educación , Cirujanos/educación , Cirugía Torácica/organización & administración , Procedimientos Quirúrgicos Torácicos/educación , Competencia Clínica , Consenso , Curriculum , Humanos , Curva de Aprendizaje , Procedimientos Quirúrgicos Robotizados/métodos , Cirujanos/organización & administración , Procedimientos Quirúrgicos Torácicos/métodos
12.
Ann Surg Oncol ; 25(4): 1069-1078, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29362963

RESUMEN

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.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Exones , Neoplasias Pulmonares/genética , Mutación , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia
14.
Ann Thorac Surg ; 104(4): 1194-1199, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28760464

RESUMEN

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.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Metástasis Linfática/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Anciano , Errores Diagnósticos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Estudios Retrospectivos , Sensibilidad y Especificidad
15.
Ann Thorac Surg ; 104(2): e207-e209, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28734456

RESUMEN

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.


Asunto(s)
Implantes Absorbibles , Clavos Ortopédicos , Trasplante de Pulmón , Esternotomía/efectos adversos , Dehiscencia de la Herida Operatoria/cirugía , Toracotomía/efectos adversos , Técnicas de Cierre de Heridas , Humanos , Esternón/cirugía , Receptores de Trasplantes
16.
JCI Insight ; 2(7): e89665, 2017 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-28405609

RESUMEN

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.


Asunto(s)
Linfocitos B/inmunología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Miastenia Gravis Autoinmune Experimental/terapia , Receptores Colinérgicos/inmunología , Adolescente , Adulto , Animales , Anticuerpos Monoclonales/sangre , Niño , Modelos Animales de Enfermedad , Femenino , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Adulto Joven
17.
Eur J Cardiothorac Surg ; 51(2): 255-262, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28186237

RESUMEN

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.


Asunto(s)
Antineoplásicos/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Proteínas Proto-Oncogénicas p21(ras)/genética , Anciano , Antineoplásicos/administración & dosificación , Bevacizumab/administración & dosificación , Biomarcadores de Tumor/genética , Quimioterapia Adyuvante , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Masculino , Metastasectomía , Persona de Mediana Edad , Mutación , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos
18.
Circ J ; 81(5): 660-667, 2017 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-28202855

RESUMEN

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.


Asunto(s)
Arritmias Cardíacas/etiología , Trasplante de Pulmón/efectos adversos , Adolescente , Adulto , Anciano , Arritmias Cardíacas/mortalidad , Fibrilación Atrial , Aleteo Atrial , Niño , Humanos , Incidencia , Trasplante de Pulmón/mortalidad , Persona de Mediana Edad , Mortalidad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo
19.
Ann Thorac Surg ; 103(3): 881-889, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28168966

RESUMEN

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.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Neumonectomía/efectos adversos , Síndrome de Dificultad Respiratoria/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Respiración Artificial , Estudios Retrospectivos
20.
Surg Endosc ; 31(3): 1250-1256, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27405483

RESUMEN

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.


Asunto(s)
Enfermedades Pulmonares/cirugía , Neumonectomía/métodos , Cirugía Torácica Asistida por Video , Anciano , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA