The Hôpital Cochin is a hospital of public assistance in the rue du Faubourg-Saint-Jacques Paris 14e. It houses the central burn treatment centre of the city. The Hôpital Cochin is a section of the Faculté de Médecine Paris-Descartes. It commemorates Jean-Denis Cochin, curé of the parish of Saint-Jacques-du-Haut-Pas and founder of a hospital for the workers and poor of that quarter of Paris.Since 1990, a biomedical research centre, the Institut Cochin, has been associated with the hospital. It was reorganised in 2002 to embrace genetic research, molecular biology and cellular biology, with a staff of about 600. It is part of both INSERM and CNRS, integrated with the Université Paris V.In 2004 the Maison de Solenn, a shelter for adolescents, was opened within the hospital with the active support of Bernadette Chirac; its name commemorates Solenn Poivre d'Arvor..
BACKGROUND:Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care. METHODS:This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively. RESULTS:Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS. CONCLUSION:Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose.
Per-oral endoscopic myotomy (POEM) achieves an 80–90
Objectives To determine whether adults with sickle cell disease (SCD) without glaucoma exhibit subclinical optic neuropathy (ON) on optical coherence tomography (OCT) and to identify genetic, clinical, and biologic correlates of optic nerve thinning. Methods Monocentric, retrospective cross-sectional study of 185 eyes from 96 adults with SCD (116 eyes/59 HbSS; 69 eyes/37 HbSC) and 40 eyes from 20 controls. Spectral-domain OCT measured Bruch’s membrane opening–minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC). ON was defined as concordant thinning across all three parameters. Patient-clustered models with Holm adjustment compared groups; multivariable clustered logistic regression identified risk factors. Results Compared with controls, SCD eyes showed thinner BMO-MRW, RNFL, and GCC (all p < 0.001). Within SCD, HbSC exhibited greater thinning than HbSS, especially in temporal and superonasal BMO-MRW sectors and RNFL average, inferotemporal, and superotemporal sectors. Proliferative SCR showed more pronounced loss than non-proliferative disease, including lower BMO-MRW, temporal RNFL thinning, and global GCC reduction. Hemoglobin correlated positively with BMO-MRW in HbSS (ρ = 0.41, p = 0.001), hematocrit tended toward a negative association with RNFL in HbSC (ρ=−0.29, p = 0.06), and reticulocytes were inversely associated with GCC in HbSS (ρ=−0.25, p = 0.038) and HbSC (ρ=−0.31, p = 0.038). Older age, recent acute chest syndrome, and ≥ 1 vaso-occlusive crisis within 2 years independently increased ON odds, whereas higher hemoglobin was protective. Conclusions Adults with SCD show OCT-detectable subclinical ON linked to genotype, retinopathy stage, anemia severity, and vaso-occlusive burden; combined BMO-MRW, RNFL, and GCC may aid risk-stratified surveillance.
The TNM classification applies to three types of thoracic tumors: lung cancer, thymic epithelial tumors (thymomas, neuroendocrine neoplasms, carcinomas), and pleural mesotheliomas. This 9th edition introduces two changes for the lung: category N2 (mediastinal lymph node metastases) is divided into N2a and N2b, when one N2 station or several N2 stations are affected, respectively, regardless of the number of lymph nodes; category M1c (multiple extrathoracic metastases) is divided into M1c1 and M1c2 when multiple extrathoracic metastases are present in one or more organs, respectively. There are no changes for category T. With regard to the thymus, the changes only concern the T descriptor with the introduction of size: T1a represents tumors ≤5cm and T1b tumors >5cm; and the invasion of the lung parenchyma and phrenic nerve becomes T2, which also includes invasion of the pericardium. Invasion of the mediastinal pleura is no longer a TNM criterion and is considered as an additional histological parameter. Regarding pleural mesotheliomas, as curative surgical resection is exceptional, the proposed changes only involve the clinical T descriptor, with no change to the pathological T descriptor or the N and M descriptors. T is defined on CT scan and depends on the sum of the maximum thickness of the pleura measured on three axial sections at the upper, middle, and lower hemithorax levels, and on the maximum pleural thickness in the fissure on a sagittal section.
El dolor crónico posquirúrgico (DCPQ) se define por una duración superior a 3 meses. Dependiendo del estudio, su incidencia varía del 3,3% al 30% a los 12 meses. Pueden dividirse en tres grupos: el grupo en el que normalmente hay poco o ningún dolor preoperatorio, a menudo asociado a lesiones nerviosas; el grupo en el que el dolor es preexistente en el momento de la cirugía, con frecuencia asociado a un mecanismo de inflamación con sus propias repercusiones psicológicas; y un grupo mixto en el que el dolor puede ser preexistente pero se exacerba en el postoperatorio, y cuyo mecanismo combina exceso de nocicepción, inflamación y dolor neuropático. Los diversos factores predictivos preoperatorios son el dolor preoperatorio, el consumo de opiáceos, la ansiedad, el catastrofismo, los antecedentes de cirugía, la existencia de dolor neuropático, etc. La investigación de los factores genéticos aún no es una práctica habitual, pero es posible realizar una fenotipificación familiar. El manejo preoperatorio se considera en el contexto de una mejor recuperación en cirugía, lo que demuestra la importancia del ñqnejo multidisciplinario. En la fase operatoria, la prevención quirúrgica es esencial para reducir la incidencia del DCPQ. En cuanto a la anestesia, la prevención farmacológica abarca la ketamina, la gabapentina, la analgesia local y locorregional, la lidocaína intravenosa, la dexametasona y los α2-agonistas. En el postoperatorio inmediato se analiza, a partir de ejemplos prácticos, la gestión de los opiáceos y otros analgésicos prescritos en el preoperatorio. La Sociedad Francesa de Anestesia y Cuidados Intensivos (Société française d'anesthésie-réanimation) recuerda el principio de la analgesia multimodal basada en analgésicos, antiinflamatorios, antihiperalgésicos y anestesia locorregional (catéter perineural y sus coadyuvantes). Por último, es esencial anticipar el alta de los pacientes y proporcionarles un seguimiento analgésico y psicológico adecuado en su domicilio. La creación de unidades y consultas especializadas en el manejo del dolor perioperatorio parece esencial para el tratamiento personalizado de estos pacientes recién operados.
