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1.
Int Rev Cell Mol Biol ; 376: 1-36, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36997266

RESUMEN

Charged particle radiotherapy, mainly using protons and carbon ions, provides physical characteristics allowing for a volume conformal irradiation and a reduction of the integral dose to normal tissue. Carbon ion therapy additionally features an increased biological effectiveness resulting in peculiar molecular effects. Immunotherapy, mostly performed with immune checkpoint inhibitors, is nowadays considered a pillar in cancer therapy. Based on the advantageous features of charged particle radiotherapy, we review pre-clinical evidence revealing a strong potential of its combination with immunotherapy. We argue that the combination therapy deserves further investigation with the aim of translation in clinics, where a few studies have been set up already.


Asunto(s)
Radioterapia de Iones Pesados , Protones , Radioterapia de Iones Pesados/métodos , Iones , Inmunoterapia , Carbono
2.
Rev Mal Respir ; 40(1): 78-93, 2023 Jan.
Artículo en Francés | MEDLINE | ID: mdl-36528503

RESUMEN

Since 2005, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a standard pulmonological tool. The procedure is safe and well tolerated by patients, with minimal morbidity and almost no mortality. A previous review on the technique was published in 2012. However, over the last ten years, a number of new studies have been published on "benign" (sarcoidosis, tuberculosis…) as well as "malignant" diseases (lung cancer, metastases of extra-thoracic cancers, search for mutations and specific oncogenic markers…). These developments have led to expanded indications for EBUS-TBNA, with which it is indispensable to be familiar, in terms of "staging" as well as "diagnosis". In view of optimizing lymph node sampling, several publications have described and discussed EBUS exploration by means of newly available tools (biopsy forceps, larger needles…), and proposed interpretation of the images thereby produced. Given the ongoing evolution of linear EBUS, it seemed indispensable that information on this marvelous tool be updated. This review is aimed at summarizing the novel elements we have found the most important.


Asunto(s)
Neoplasias Pulmonares , Mediastino , Humanos , Mediastino/patología , Broncoscopía/métodos , Neoplasias Pulmonares/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Endoscopía , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Estudios Retrospectivos
5.
Diagn Interv Imaging ; 101(11): 739-746, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32739123

RESUMEN

PURPOSE: The purpose of this study was to identify sagittal spinopelvic parameters predictive of adjacent segment disease (ASD) on postoperative whole spine weight-bearing stereoradiography. MATERIALS AND METHODS: A total of 84 patients with previous spinal fusion surgery and documented radiological follow-up with early weight-bearing postoperative whole spine stereoradiography (EOS® Imaging System) were retrospectively included. A pathological group of 42 patients (9 men, 33 women; mean age, 63.1±11.5 [SD] years) who developed documented ASD (mean follow-up, 76.75 months; range: 31.5-158.5 months) was compared with a control group of 42 asymptomatic patients (7 men, 35 women; mean age, 60.9±11.8 [SD] years) (mean follow-up, 115 months; range: 60-197 months) based on sagittal balance evaluation and routinely used spino-pelvic parameters. Comparisons were made using uni- and multivariate analyses. RESULTS: At univariate analysis, patients with ASD had an anteriorly displaced sagittal vertical axis (CAM plumb line) and an inadequate lumbar lordosis (LL) in reference to pelvic incidence (PI) compared to controls. They also had higher C7 slope and C2-C7 offset. At multivariate analysis, C2-C7 offset (OR=1.152; 95% CI: 1.056-1.256; P=0.001) and a lack of LL (OR=5.063; 95% CI: 1.139-22.498; P=0.033) were significantly associated with ASD. CONCLUSION: Anterior cervical imbalance, reflected by an increase in C2-C7 offset and insufficient restoration of LL are postoperative predictive factors of ASD on stereoradiography.


Asunto(s)
Lordosis , Femenino , Humanos , Lordosis/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Pelvis/diagnóstico por imagen , Periodo Posoperatorio , Radiografía , Estudios Retrospectivos
6.
Cuad. Hosp. Clín ; 61(1): [11], jul. 2020. ilus.
Artículo en Español | LILACS, LIBOCS | ID: biblio-1118902

RESUMEN

Los tumores de células gigantes (TDG) llamados también osteoclastomas o tumores pardos cuando se hallan dentro la esfera endocrinológica, son uno de los tumores menos frecuentes, más controversial y menos predecible en su comportamiento. Se producen como consecuencia del exceso de la actividad osteoclastica, como ocurre en el caso del hiperparatiroidismo, mismo que es un desorden endocrino común, por lo general asintomático y diagnosticado por el hallazgo fortuito de hipercalcemia. El diagnóstico de los osteoclastomas suele ser un reto, el alto índice de sospecha es esencial y la biopsia es el estándar de oro para el diagnóstico. Presentamos el caso de un hombre de 42 años quien presentó fracturas patológicas de radio derecho y tibia izquierda, gammagrama óseo con Tc ­ 99m con múltiples lesiones óseas , hormona paratiroidea (PTH) elevada, hipercalcemia, gammagrama de paratiroides con MIBI con presencia de adenoma paratiroideo, la biopsia de las lesiones óseas con presencia de células gigantes multinucleadas correspondientes a osteoclastomas; se llevó a cabo paratiroidectomia y el examen histopatológico confirmó la presencia de un adenoma paratiroideo.


Giant cell tumors (TDG), also called osteoclastomas or brown tumors when they are within the endocrinological sphere, are one of the least frequent, most controversial and least predictable tumors in their behavior. They occur as a consequence of excess osteoclastic activity, as occurs in the case of hyperparathyroidism, which is a common endocrine disorder, generally asymptomatic and diagnosed by the fortuitous finding of hypercalcemia. Diagnosing osteoclastomas is usually challenging, the high index of suspicion is essential, and biopsy is the gold standard for diagnosis. We present the case of a 42-year-old man who presented pathological fractures of the right radius and left tibia, a bone scan with Tc-99m with multiple bone lesions, elevated parathyroid hormone (PTH), hypercalcemia, parathyroid scan with MIBI with the presence of parathyroid adenoma, the biopsy of the bone lesions with the presence of multinucleated giant cells corresponding to osteoclastomas; parathyroidectomy was performed and histopathological examination confirmed the presence of a parathyroid adenoma.


Asunto(s)
Masculino , Adulto , Heridas y Lesiones , Biopsia , Diagnóstico , Hipercalcemia
8.
Nat Commun ; 10(1): 3407, 2019 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-31431620

RESUMEN

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.


Asunto(s)
Biomarcadores de Tumor/genética , Tumor Carcinoide/genética , Carcinoma de Células Grandes/genética , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tumor Carcinoide/mortalidad , Tumor Carcinoide/patología , Carcinoma de Células Grandes/mortalidad , Carcinoma de Células Grandes/patología , Hibridación Genómica Comparativa , Conjuntos de Datos como Asunto , Femenino , Genómica , Proteínas de Homeodominio/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Aprendizaje Automático , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Tasa de Supervivencia , Adulto Joven
9.
Respir Med Res ; 75: 1-4, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31235451

RESUMEN

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.


Asunto(s)
Broncoscopía/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/secundario , Mediastino/patología , Neoplasias/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Biopsia Guiada por Imagen/métodos , Ganglios Linfáticos/diagnóstico por imagen , Linfadenopatía/diagnóstico , Linfadenopatía/etiología , Metástasis Linfática , Masculino , Mediastinoscopía/métodos , Mediastino/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias/diagnóstico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
10.
Rev Mal Respir ; 36(4): 455-460, 2019 Apr.
Artículo en Francés | MEDLINE | ID: mdl-31005425

RESUMEN

INTRODUCTION: In the diagnostic approach to interstitial lung disease (ILD), the use of transbronchial cryobiopsy (TBC) may offer an alternative to surgical lung biopsy (SLB). We report the diagnostic effectiveness and the safety of TBC in ILD based on the preliminary experience in two French university centers. METHODS: Twenty four patients underwent TBC for the diagnosis of ILD in the operating room between 2014 and 2017. All the histological diagnoses obtained were then reviewed and validated during multidisciplinary discussions (MDD). RESULTS: Patients had an average of 3 TBC.TBC samples were analyzable in 22/24 (91.7%) patients. In these, samples allowed a histological diagnosis to be made in 14/22 (63.6%) patients and a diagnosis with certainty in 13/22 (59%) after MDD. The overall diagnostic yield from TBC was 13/24 (54.2%). Nine (37.5%) patients had a pneumothorax. Five (20.8%) patients had a bleeding. There were no deaths. Taking into account a possible initial learning curve and considering only the 15 patients who had their TBC after 2015, we note that a diagnosis could be made after MDD for 12 of them, that is, 80%. CONCLUSION: A prospective randomized study is needed to evaluate the technique in France in order to specify its diagnostic performance and its safety profile in comparison to SLB.


Asunto(s)
Broncoscopía/métodos , Enfermedades Pulmonares Intersticiales/diagnóstico , Pulmón/patología , Anciano , Anestesia General/efectos adversos , Anestesia General/métodos , Biopsia/efectos adversos , Biopsia/métodos , Biopsia/estadística & datos numéricos , Broncoscopía/efectos adversos , Broncoscopía/estadística & datos numéricos , Criobiología/métodos , Femenino , Francia/epidemiología , Humanos , Tiempo de Internación/estadística & datos numéricos , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
11.
Neurogenetics ; 19(2): 93-103, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29511999

RESUMEN

Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.


Asunto(s)
Discapacidad Intelectual/genética , Complejo Mediador/genética , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Masculino , Mutación Missense , Fenotipo
12.
Andrology ; 6(3): 436-445, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29499098

RESUMEN

The purpose of this study was to investigate the relationship between the proportion of sperm chromatin linked to remaining histone and assisted reproductive technology (ART) outcome. A prospective cohort study was performed on couples undergoing ART process at the Department of Reproduction Medicine (HFME, Bron, France). The histone-to-protamine ratio (HPR) was measured using the method described by Wykes & Krawetz (2003) J Biol Chem 278, 29471. The correlations with sperm DFI, blastocyst formation, pregnancy rate, and delivery rate were investigated. A total of 291 ART cycles were included (42 c-IVF and 249 ICSI procedures): 3870 oocytes were punctured and 2211 embryos were obtained, among which 507 were transferred and 336 frozen. The mean HPR was 18.9%. A significant negative correlation was found between HPR and DFI (r = -0.12, p < 0.05). Regarding the type of ART procedure (c-IVF or ICSI), the same kind of relationship between HPR and ART parameters was observed. Regardless of the type of ART procedure used, when the HPR was within the range [6%; 26%], the blastocyst formation rate was higher: 87.8% vs. 71.2% (HPR<6%; p < 0.01) and 74.6% (HPR >26%; p < 0.01). The highest delivery rate (DR; 24.5%) was obtained for HPR within the range [6%; 26%]; DR was 21.9% for HPR<6% and 18.3% for HPR>26%; however, the differences were not statistically significant. The procedure described in this study seems to be a reliable evaluation of the HPR. The HPR parameter seems to be correlated to embryonic development up to the blastocyst stage, but its involvement in clinical pregnancy/delivery could not be confirmed. HPR should be further investigated for confirming the relationship with blastocyst formation. After this, the next step will be to investigate the etiologies of HPR alterations for improving the sperm nucleus quality for increasing the chance of pregnancy.


Asunto(s)
Cromatina , Desarrollo Embrionario , Histonas , Protaminas , Técnicas Reproductivas Asistidas , Espermatozoides , Adulto , Cromatina/metabolismo , Cromatina/patología , Estudios de Cohortes , Femenino , Histonas/metabolismo , Humanos , Masculino , Embarazo , Índice de Embarazo , Estudios Prospectivos , Protaminas/metabolismo , Espermatozoides/metabolismo , Espermatozoides/patología
13.
J Viral Hepat ; 25(1): 63-71, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28772350

RESUMEN

Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.


Asunto(s)
Apolipoproteínas E/metabolismo , Claudina-1/metabolismo , Hepacivirus/crecimiento & desarrollo , Hepatocitos/fisiología , Hepatocitos/virología , MicroARNs/metabolismo , Apolipoproteínas E/genética , Línea Celular Tumoral , Claudina-1/genética , Humanos , MicroARNs/genética , Transducción Genética
14.
Eur J Clin Microbiol Infect Dis ; 36(3): 523-528, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27815777

RESUMEN

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.


Asunto(s)
Quemaduras/complicaciones , Portador Sano/microbiología , Neumonía Estafilocócica/epidemiología , Staphylococcus aureus/aislamiento & purificación , Heridas y Lesiones/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Estafilocócica/microbiología , Neumonía Estafilocócica/terapia , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo
15.
Osteoporos Int ; 27(11): 3365-3376, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27341811

RESUMEN

Chronic protein malnutrition leads to child mortality in developing countries. Spirulina alga (Spi), being rich in protein and growing easily, is a good candidate as supplementation. We showed that Spi completely prevents bone growth retardation and liver disturbances observed in young rats fed a low protein diet. This supports Spi as a useful source of vegetable protein to fight against protein malnutrition. INTRODUCTION: Chronic malnutrition is a main factor of child mortality in developing countries. A low protein diet impairs whole-body growth and leads to fatty liver in growing rats. Spi has great potential as a supplementation as it has a 60 % protein content and all essential amino acids. However, its specific impact on bone growth and the related secretion of hepatokines have not yet been studied. METHODS: To address this question, 6-week-old female rats were fed isocaloric diets containing 10 % casein, 5 % casein, or 5 % casein + 5 % protein from Spi during 9 weeks. Changes in tibia geometry, microarchitecture, BMC, BMD, and biomechanical properties were analyzed. Serum IGF-I, FGF21, follistatin, and activin A were assessed as well as their hepatic gene expressions in addition to those of Sirt1, Ghr, and Igf1r. Hepatic fat content was also assessed. RESULTS: A low protein diet altered bone geometry and reduced proximal tibia BMD and trabecular bone volume. In addition, it increased hepatic fat content and led to hepatic GH resistance by decreasing serum IGF-I and increasing serum FGF21 without altering serum activin A and follistatin. Spi prevented low protein diet-induced bone, hepatic, and hormonal changes, and even led to higher biomechanical properties and lower hepatic fat content in association with specific InhbA and Follistatin expression changes vs. the 10 % casein group. CONCLUSIONS: Altogether our results demonstrate the preventive impact of Spi on bone growth delay and hepatic GH resistance in conditions of isocaloric dietary protein deficiency.


Asunto(s)
Desarrollo Óseo , Suplementos Dietéticos , Hígado Graso/prevención & control , Spirulina , Activinas/sangre , Animales , Dieta con Restricción de Proteínas/efectos adversos , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Folistatina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratas , Ratas Sprague-Dawley
16.
Am J Transplant ; 16(10): 3024-3032, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27273845

RESUMEN

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement.


Asunto(s)
Biomarcadores/análisis , Tasa de Filtración Glomerular , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Donadores Vivos , Adulto , Femenino , Estudios de Seguimiento , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
17.
Rev Mal Respir ; 33(9): 751-756, 2016 Nov.
Artículo en Francés | MEDLINE | ID: mdl-27017063

RESUMEN

BACKGROUND: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma. METHODS: This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy. RESULTS: Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001. CONCLUSION: An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Biomarcadores de Tumor/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Terapia Molecular Dirigida , Oncogenes , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Crizotinib , Detección Precoz del Cáncer/métodos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Receptor ErbB-2/genética , Análisis de Supervivencia , Factores de Transcripción/genética
18.
Clin Microbiol Infect ; 22(5): 438-43, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26802215

RESUMEN

Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [(18)F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for ≥12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [(18)F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI.


Asunto(s)
Fluorodesoxiglucosa F18/administración & dosificación , Meningitis/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Sensibilidad y Especificidad
19.
Target Oncol ; 11(2): 167-74, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26315967

RESUMEN

UNLABELLED: Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67 ± 12.7 years, women: 69 %, non smokers: 68 %, PS 0-1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients. CLINICAL TRIAL INFORMATION: NCT02293733.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Mutación , Estudios Retrospectivos
20.
Rev Mal Respir ; 32(5): 477-84, 2015 May.
Artículo en Francés | MEDLINE | ID: mdl-26072007

RESUMEN

INTRODUCTION: Endobronchial resection is now the standard treatment for tracheobronchial narrowing due to malignancy. The clinical and functional respiratory improvement has been evaluated previously but only in heterogeneous population. METHODS: Between February 2009 and February 2011, we conducted a prospective single centre study at the University Hospital of Lille. Twenty-five patients with malignant tracheobronchial stenosis received a clinical and functional respiratory evaluation before and after a rigid bronchoscopy procedure to reduce the obstruction followed where appropriate by placement of an endobronchial stent. RESULTS: Thirteen patients (52%) had primary lung cancer and in 12 the tumor had another origin. Nineteen patients (76%) received a stent after bronchial unblocking. Clinically, all patients felt an improvement in their dyspnea estimated by the Borg score with a median improvement of -2 points [-1; -4] following the procedure (P<0.001). In 96% the dyspnea visual analogic scale improved by 40 mm [27; 67] (P<0.0001). The FEV1 increased significantly after unblocking by 9% [-3.5; 28.5] (P<0.05). The Rint decreased significantly by -0.19 kPa/L per second [-0.06; -0.023] (P=0.001). Correlations between scales of dyspnea and spirometric values were not significant (P>0.05). The survival rate at 1 year was 29%. CONCLUSION: Interventional bronchoscopy decreases dyspnea. It modestly improves respiratory function and decreases the Rint. However, lung function and dyspnea scales are not correlated. No spirometry factor can predict clinical dyspnea response but an elevated Borg dyspnea scale might be a good indicator.


Asunto(s)
Obstrucción de las Vías Aéreas/cirugía , Broncoscopía/métodos , Carcinoma/cirugía , Neoplasias Pulmonares/cirugía , Anciano , Obstrucción de las Vías Aéreas/etiología , Resistencia de las Vías Respiratorias , Broncoscopios , Broncoscopía/instrumentación , Carcinoma/complicaciones , Carcinoma/secundario , Constricción Patológica , Disnea/etiología , Neoplasias Esofágicas/patología , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Estudios Prospectivos , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Espirometría , Stents
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