•This study describes a sensitive and accurate ELISA method for quantification of nivolumab in human plasma.•Plasma concentration of nivolumab was assayed in non-small-cell lung cancer patients.•The ...assay is applicable to investigate pharmacokinetics of nivolumab and its PK/PD relationship.•Endogenous IgG level contributes to the interindvidual variability in nivolumab pharmacokinetics.
Nivolumab, an anti PD-1 monoclonal antibody, has been approved for the treatment of previously treated advanced or metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to develop and validate an ELISA method for the quantification of nivolumab in plasma from patients with NSCLC in order to perform future pharmacokinetic/pharmacodynamic (PK/PD) studies. A home-made ELISA was developed and validated according to the general recommendations for the immunoassays. Then, the ELISA method was applied to quantify plasma trough levels (Cmin) of nivolumab (3mg/kg every two weeks) in 27 NSCLC patients at days 14, 28 and 42 after start of treatment. Blood samples were collected just before the infusion on days 0 (baseline), 14, 28 and 42 after start of treatment. The dynamic calibration range for nivolumab assay was 5–100μg/mL. Within- and between-day imprecision for quality controls (5, 20 and 75μg/mL) were less than 5 and 12%, respectively. The mean (±standard deviation) nivolumab Cmin was 17.3±4.8μg/mL (coefficient of variation, CV=27.8%), 25.0±9.7μg/mL (CV=38.8%) and 33.0±12.9μg/mL (CV=39.1%) on days 14, 28 and 42, respectively. IgG (p=0.002) and ALT (p=0.041) were independently associated with plasma nivolumab Cmin at day 42. The present ELISA method for quantification of nivolumab in plasma from NSCLC patients is sensitive and accurate enough to be used for further PK/PD investigations.
Orbital lesions are rare but serious. Their characterization remains challenging. Diagnosis is based on biopsy or surgery, which implies functional risks. It is necessary to develop noninvasive ...diagnostic tools. The goal of this study was to evaluate the diagnostic performance of dynamic contrast-enhanced MR imaging at 3T when distinguishing malignant from benign orbital tumors on a large prospective cohort.
This institutional review board-approved prospective single-center study enrolled participants presenting with an orbital lesion undergoing a 3T MR imaging before surgery from December 2015 to May 2021. Morphologic, diffusion-weighted, and dynamic contrast-enhanced MR images were assessed by 2 readers blinded to all data. Univariable and multivariable analyses were performed. To assess diagnostic performance, we used the following metrics: area under the curve, sensitivity, and specificity. Histologic analysis, obtained through biopsy or surgery, served as the criterion standard for determining the benign or malignant status of the tumor.
One hundred thirty-one subjects (66/131 50% women and 65/131 50% men; mean age, 52 SD, 17.1 years; range, 19-88 years) were enrolled. Ninety of 131 (69%) had a benign lesion, and 41/131 (31%) had a malignant lesion. Univariable analysis showed a higher median of transfer constant from blood plasma to the interstitial environment (
) and of transfer constant from the interstitial environment to the blood plasma (minute
) (Kep) and a higher interquartile range of
in malignant-versus-benign lesions (1.1 minute
versus 0.65 minute
,
= .03; 2.1 minute
versus 1.1 minute
,
= .01; 0.81 minute
versus 0.65 minute
,
= .009, respectively). The best-performing multivariable model in distinguishing malignant-versus-benign lesions included parameters from dynamic contrast-enhanced imaging, ADC, and morphology and reached an area under the curve of 0.81 (95% CI, 0.67-0.96), a sensitivity of 0.82 (95% CI, 0.55-1), and a specificity of 0.81 (95% CI, 0.65-0.96).
Dynamic contrast-enhanced MR imaging at 3T appears valuable when characterizing orbital lesions and provides complementary information to morphologic imaging and DWI.
Objectif : Des consultations avancées avaient été identifiées lors d’un état des lieux des coopérations ville-hôpital réalisé en 2016 à l’Assistance publique – Hôpitaux de Paris. L’étude réalisée ...vise à apprécier leurs avantages et inconvénients. Méthodes : Des entretiens ont été menés avec les praticiens réalisant les consultations, les chefs de service, les directions (hôpitaux et centres de santé). Un recueil quantitatif a été réalisé pour sept consultations. Résultats : Ces consultations proposaient des soins en secteur 1 dans des zones défavorisées, le recours à une structure de taille plus humaine que l’hôpital et des délais de rendez-vous parfois plus courts. Pour les praticiens, elles permettaient une diversification de l’activité et une découverte de la médecine de ville. Pour le service hospitalier, elles engendraient le recrutement éventuel de patients et un déport du suivi vers le centre de santé pour les patients vivant à proximité. Il ressort que ces consultations permettent de renforcer des liens ville-hôpital déjà existants et informels. Parmi les difficultés, on note l’absence d’interopérabilité des systèmes d’information, la difficulté à mobiliser certains professionnels et une augmentation de la charge de travail. Conclusion : La mise en place de consultations avancées, si elle peut constituer une première étape dans l’organisation des liens entre la ville et l’hôpital, ne permet pas à elle seule d’assurer un maillage territorial. Les partenariats doivent s’élargir à plusieurs centres mais aussi à d’autres structures de ville. Par ailleurs, des partenariats plus larges permettent de formaliser des parcours de soins.
Importance:
An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of ...the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and could improve the clinical outcomes as an adjunct treatment. We proposed to test it by the stimulation of the auricular branch of the vagus nerve, i.e., auricular neuromodulation (AN), a non-invasive procedure through the insertion of semipermanent needles on the ears.
Objective:
The aim of this study was to assess the effect of AN on the clinical outcomes in patients affected by COVID-19.
Design, Setting, and Participants:
A multicenter, randomized, placebo-controlled, double-blind clinical trial included 31 patients with respiratory failure due to COVID-19 requiring hospitalization. Within 72 h after admission, patients received either AN (
n
= 14) or sham neuromodulation (SN,
n
= 15) in addition to the conventional treatments.
Main Outcome and Measures:
The primary endpoint of the study was the rate of a clinical benefit conferred by AN at Day 14 (D14) as assessed by a 7-point Clinical Progression Scale. The secondary endpoint of the study was the impact of AN on the rate of transfer to the intensive care unit (ICU) and on the survival rate at D14.
Results:
The AN procedure was well-tolerated without any reported side effects but with no significant improvement for the measures of both primary (
p
> 0.3) and secondary (
p
> 0.05) endpoints at the interim analysis. None of the AN-treated patients died but one in the SN group did (81 years). Two AN-treated patients (73 and 79 years, respectively) and one SN-treated patient (59 years) were transferred to ICU. Remarkably, AN-treated patients were older with more representation by males than in the SN arm (i.e., the median age of 75 vs. 65 years, 79% male vs. 47%).
Conclusion:
The AN procedure, which was used within 72 h after the admission of patients with COVID-19, was safe and could be successfully implemented during the first two waves of COVID-19 in France. Nevertheless, AN did not significantly improve the outcome of the patients in our small preliminary study. It is pertinent to explore further to validate AN as the non-invasive mass vagal stimulation solution for the forthcoming pandemics.
Clinical Trial Registration:
https://clinicaltrials.gov/
, identifier NCT04341415.
Objectives
To assess the accuracy of magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS) fusion to guide first‐round biopsies in the diagnosis of localised prostate cancer (PCa) in ...men with a prostate‐specific antigen (PSA) ≤10 ng/mL.
Patients and Methods
A prospective study was conducted on men who met the following criteria: first‐round biopsy, multiparametric MRI (mpMRI) showing a lesion with a Likert score ≥2 and a PSA <10 ng/mL. All men underwent a extended 12‐core protocol plus a protocol of two or three targeted cores on the mpMRI index lesion. The UroStation™ (Koelis, Grenoble, France) and a V10 ultrasound system with an end‐fire three‐dimensional TRUS transducer were used for the fusion imaging procedure. Significant PCa was defined as: at least one core with a Gleason score of 3 + 4 or 6 with a maximum cancer core length ≥4 mm.
Results
A total of 152 men, whose median PSA level was 6 ng/mL, were included in the study. The proportion of positive cores was significantly higher with the targeted‐core protocol than with the extended 12‐core protocol (P < 0.001). The proportion of men with clinically significant PCa was higher with the targeted‐core protocol than with the extended 12‐core protocol (P = 0.03). The proportion of patients having at least one positive biopsy (targeted‐core protocol) was significantly different among the Likert score categories (P < 0.001).
Conclusions
For the first round of biopsies, MRI/TRUS‐fusion targeted biopsies detected more men with clinically significant PCa than did standard extended 12‐core biopsy alone.
Abstract Background Both surgeon and hospital procedure volumes have been found to be associated with total hip arthroplasty (THA) outcomes. However, little research has been conducted on the ...relative influence. We studied the association between THA survivorship and both hospital and surgeon procedure volumes, considering their relative impact. Methods A population-based cohort included all patients aged ≥40 years having received a unilateral primary THA from 2010 to 2011, from the French National Health Insurance Database. Patients were followed up until the end of 2014. The outcome was THA revision. Exposures of interest were procedure volumes, divided into tertiles: <1.5, 1.5-4, >4 and <7, 7-15, >15 procedures per month defined as low, medium, and high volumes for surgeon and hospital, respectively. Results The cohort had 62,906 patients, with mean age 69 years and women 57%. Mean surgeon and hospital volumes were 8 and 23 procedures per month, respectively, and 5%, 72%, 22% and 7%, 28%, 65% of THAs were implanted by a low-, medium-, and high-volume surgeon or in a low-, medium-, and high-volume hospital, respectively. Median follow-up was 45 months (range, 0-57 months). In multivariate analysis, adjusted for both surgeon and hospital volumes, for patient and THA characteristics, a lower surgeon volume was associated with poorer THA survivorship (adjusted hazard ratio aHR = 1.19; 95% confidence interval CI, 1.07-1.34 and aHR = 1.70; 95% CI, 1.40-2.05, for medium- and low-volume surgeon, respectively, compared with that of high volume), whereas hospital volume was not. Conclusion This study brings evidence to support the notion that THAs performed by high-volume surgeons in French private hospitals have higher survivorship in the first 4 years.
Atypical Foveal Hypoplasia in Best Disease Moret, Emmanuelle; Lejoyeux, Raphaël; Bonnin, Sophie ...
Journal of personalized medicine,
02/2023, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
To determine the prevalence and characteristics of foveal hypoplasia (also called fovea plana) in patients with Best disease using spectral-domain (SD) optical coherence tomography (OCT) and ...OCT-angiography (OCT-A).
A retrospective observational study including patients diagnosed with Best disease.
Fifty-nine eyes of thirty-two patients (fifteen females (46.9%) and seventeen males (53.1%),
= 0.9) diagnosed with Best disease were included. Patients' eyes were categorized into two groups: Eyes with a fovea plana appearance ('FP group') and eyes without fovea plana appearance ('no FP group'), based on the foveal appearance on B-scan SD-OCT.
Cross-sectional OCT images were assessed for the persistence of inner retinal layers (IRL) and OCT-A was analyzed for the presence of a foveal avascular zone (FAZ), the size of which was determined when applicable.
Overall, 16 eyes (27.1%) of 9 patients had a fovea plana appearance ('FP group') with the persistence of IRL, and 43 eyes (72.9%) of 23 patients did not have fovea plana appearance ('no FP group'). Among FP eyes, OCT-A performed in 13 eyes showed bridging vessels through the FAZ in 100% of eyes with OCT-A. Using Thomas classification, 14 out of the 16 eyes with fovea plana (87.5%) had atypical foveal hypoplasia, and the 2 others (12.5%) had a grade 1b fovea plana.
In our series, foveal hypoplasia was present in 27.1% of patients with Best disease. OCT-A showed bridging vessels through the FAZ in all eyes. These findings highlight the microvascular changes associated with Best disease, which can be an early sign of the disease in patients with a family history.
Les lésions orbitaires sont rares mais graves, notamment en raison du risque fonctionnel. La caractérisation des lésions orbitaires reste difficile et le diagnostic basé sur la biopsie, geste risqué. ...Il est nécessaire de développer des outils diagnostiques non invasifs.
L'objectif de cette étude était de déterminer la performance diagnostique de l'imagerie de perfusion Dynamic Contrast Enhanced (DCE) en IRM 3Tesla pour la caractérisation des lésions orbitaires.
Cette étude prospective monocentrique approuvée par l'IRB a recruté des patients présentant une lésion orbitaire, ayant eu une IRM 3Tesla avant chirurgie, entre décembre 2015 et mai 2021. Des séquences morphologiques, de diffusion et de perfusion DCE ont été effectuées. Des analyses bivariées puis multivariées ont été réalisées, en considérant les lésions malignes versus bénignes puis les lymphomes versus les inflammations.
131 patients (66/131 (50 %) femmes et 65/131 (50 %) hommes, âge moyen 52 ± 17 ans 19-88) ont été recrutés. L'analyse bivariée a montré des médianes de Ktrans et de Kep plus élevées pour les lésions malignes par rapport aux lésions bénignes (1,1 min−1 versus 0,65 min−1, p=0,03 et 2,1 min−1 versus 1,1 min−1, p=0,01) et pour les lymphomes par rapport aux inflammations orbitaires (1,2 min−1 versus 0,6 min−1, p=0,001 et 2,3 min−1 versus 1,1 min−1, p<0,001). En multivarié, le modèle le plus performant pour distinguer les lésions malignes des lésions bénignes incluait des paramètres de DCE, d'ADC et d'imagerie morphologique, avec une AUC de 0,81 0,67-0,96, une sensibilité de 0,82 0,55-1 et une spécificité de 0,81 0,65-0,96. Ce modèle avait une AUC de 0,84 0,65-0,1, une sensibilité de 0,83 0,5-1 et une spécificité de 0,85 0,62-1 pour distinguer lymphomes et inflammations orbitaires.
L'imagerie de perfusion Dynamic Contrast Enhanced peut être utile pour caractériser les lésions orbitaires, seule ou combinée à l'imagerie morphologique et de diffusion.
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