To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by ...immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-β42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD.
To the Editor:
In a trial of initial therapy for advanced melanoma, Tawbi et al. (Jan. 6 issue)
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found that dual blockade of lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) with ...relatlimab and nivolumab resulted in an improved outcome as compared with nivolumab therapy alone (hazard ratio for progression or death, 0.75; 95% confidence interval CI, 0.62 to 0.92). The incidence of treatment-related adverse events of grade 3 or 4 in the relatlimab–nivolumab group (18.9%, vs. 9.7% in the nivolumab group) in this trial (RELATIVITY-047) compares favorably with the incidence that was observed with nivolumab plus ipilimumab (55.0%) . . .
Biodegradable interpenetrating polymer networks (IPNs) were conceived. Polyvinyl alcohol (PVA) was chosen as synthetic polymer network in which serum albumin (SA) was added to allow the material ...forthcoming degradation by enzymes. The PVA–SA co-networks were synthesized by free radical copolymerization of polyvinyl alcohol (PVAm) and serum albumin (SAm), both previously modified with methacrylate functions. Fibrin gel which plays a key role in wound healing and hemostasis, was selected as second partner in the IPN. Fibrin/PVA–SA IPNs were synthesized rapidly through an in situ process and they are easy to handle. The homogeneous distribution of SA and fibrin in the IPN was checked by confocal laser scanning microscopy. As expected, the copolymerization of SA with PVA allows enzyme hydrolysis of both the co-networks and the corresponding IPNs with rates depending on the total protein concentration, following the Michaelis–Menten kinetic model. IPN proteolysis is therefore easily tunable. This original approach allows for the production of IPNs enzymatically degradable. Finally, these biodegradable IPNs are good supports for cell growth because their degradability enhances viability of fibroblasts cultured on their top compared to non-biodegradable material. As they mimic the physiological microenvironment of tissues, they are promising candidates for tissue engineering.
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•Biodegradable materials with interpenetrating polymer network (IPN) architecture.•Co-networks of methacrylate-modified polyvinyl alcohol (PVA) and serum albumin (SA).•Enzymatically degradable PVA-co-BSA/fibrin interpenetrating polymer networks (IPNs).•IPN's hydrolysis depends on protein content and follows the Michaelis–Menten model.•Biodegradable fibrin-based IPNs as good supports for cell growth.
L’endocardite infectieuse (EI) sur valve native est une pathologie rare mais grave. Le pronostic dépend de la rapidité du diagnostic. Il repose actuellement sur les critères de Duke modifié, où ...l’échocardiographie conserve une place majeure, mais peut manquer de sensibilité, notamment quand les valves sont remaniées. Pour les valves prothétiques, les recommandations de l’ESC 2015 ont ajouté la TEP-TDM au 18F-FDG comme critère majeur d’imagerie. L’objectif de cette étude est d’évaluer les performances diagnostiques de la TEP-TDM au 18F-FDG dans l’EI sur valve native.
Il s’agit d’une étude rétrospective concernant 59 patients du CHU de Bordeaux hospitalisés pour suspicion d’EI sur valve native entre 2011 et 2019 et ayant bénéficié d’une TEP-TDM au 18F-FDG. La probabilité d’EI était évaluée à la phase initiale selon les critères de Duke. Le diagnostic final était établi selon les critères de Duke à 3 mois de la prise en charge et était considéré comme gold standard. Les TEP-TDM ont été relues en aveugle conjointement par un junior et un senior de médecine nucléaire.
Cinquante-neuf patients ont été inclus. À 3 mois, 26 patients avaient une EI « certaine », 22 patients avaient une « EI rejetée » et 11 patients avaient une EI « possible ». Douze patients avaient une TEP-TDM au 18F-FDG positive au niveau valvulaire. La sensibilité des critères de Duke modifiés à la phase initiale était de 77 % et la spécificité de 81 %. La sensibilité de la TEP-TDM au 18F-FDG seule était de 46 %. La sensibilité des critères de Duke en ajoutant la TEP-TDM au 18F-FDG était augmentée à 96 % avec conservation de la spécificité à 81 %. Tous les patients classés EI certaine à 3 mois avec un abcès para-valvulaire diagnostiqué à l’échographie cardiaque avaient une TEP-TDM positive. Quatorze patients (54 %) des EI certaines à 3 mois avaient au moins un embole à distance diagnostiqué sur la TEP-TDM.
L’ajout de la TEP-TDM au 18F-FDG aux critères de Duke modifiés permet d’augmenter la sensibilité dans le diagnostic d’endocardite infectieuse sur valve native à la phase initiale, en plus de son apport dans le bilan d’extension. Il aide au diagnostic d’abcès para-valvulaire.
Native valve endocarditis (NVE) is a rare but serious disease. The prognosis depends on the rapidity of diagnosis, and is currently based on modified Duke criteria, where echocardiography has a key role but may lack sensitivity if valves are calcified. For prosthetic valves, the European Society of Cardiology 2015 recommendations added 18F-FDG PET/CT as a major imaging criterion as well as for extension assessment. This study evaluated the diagnostic accuracy of 18F-FDG PET/CT in NVE and in extension assessment.
This retrospective study involved 59 patients suspected of NVE at Bordeaux university hospital between 2011 and 2019 and received 18F-FDG PET/CT. The final diagnosis was established according to Duke criteria after 3 months of management. Infective endocarditis (IE) was assessed in the initial phase according to the Duke criteria. All PET/CTs were blindly reviewed jointly by a junior and senior nuclear-medicine physician.
In total, 59 patients were included. At 3 months, 26 patients had definite IE, 22 had rejected IE, and 11 possible IE. Twelve patients had positive PET/CT results. The sensitivity of the modified Duke criteria in the initial phase was 77% and the specificity was 81%. When combined with 18F-FDG PET/CT, the sensitivity of the Duke criteria increased to 96% and the specificity was 81%. The sensitivity of 18F-FDG PET/CT alone was 46%. All three patients with perivalvular abscess had positive PET/CT results. Of the 22 patients with NVE definite at 3 months, fourteen (54%) had at least one septic embolism diagnosed on PET/CT.
The implementation of 18F-FDG PET/CT with modified Duke criteria increased the sensitivity for NVE diagnosis in the initial phase and contributed to IE extension assessment. It may contribute to making the diagnosis of a local cardiac complication.
The purpose of this study was to evaluate MRI and fluorocholine PET/CT diagnostic performances for the detection of local recurrence following prostate brachytherapy for localised prostate cancer.
In ...this single-centre study, we retrospectively reviewed data from 21 patients treated by brachytherapy for localised prostate cancer and diagnosed with biochemical recurrence according to Phoenix Criteria, who underwent MRI and fluorocholine PET/CT. We included patients with local relapse suspicion according to imaging exams, with biopsy for the final assessment of local recurrence. Patient analysis data were supplemented by segment analysis using an 8-segment model.
The fluorocholine PET/CT was positive for 81% and negative for 19% of patients. The sensitivity and specificity were 92% and 33% with diagnosis accuracy of 67%. The MRI was positive for 57% and negative for 43% of patients. The sensitivity and specificity were 67% and 56% with diagnosis accuracy of 62%. There was no statistically significant difference between fluorocholine PET/CT and MRI accuracy (P=0.63). On a segment-based analysis, the sensitivity and specificity were 44% and 82% for fluorocholine PET/CT with diagnosis accuracy of 78%. For MRI, specificity was 91% diagnosis accuracy was 82%.
Both MRI and fluorocholine PET/CT permit to highlight local recurrence sites after prostate brachytherapy. Confirmation biopsies are, however, necessary since this accuracy is insufficient.
L’objectif de ce travail était d’évaluer les performances de la tomographie par émission de positons (TEP)–scanographie à la (18F)-fluorocholine ou l’IRM en cas de rechute biochimique après curiethérapie d’un cancer de la prostate localisé, qui sont peu décrites dans la littérature.
Il s’agit d’une étude monocentrique rétrospective incluant 21 patients pris en charge par curiethérapie pour un cancer de la prostate localisé en rechute biochimique selon les critères de Phoenix. Tous les patients ont eu une IRM et une TEP–scanographie à la (18F)-fluorocholine. Nous avons inclus les patients avec une suspicion de la rechute locale selon l’imagerie et pour qui une biopsie confirmait le diagnostic d’adénocarcinome de prostate. Un modèle d’analyse par patient et par segment a été utilisé.
La TEP–scanographie à la (18F)-fluorocholine était positive chez 81% des patients, négative chez 19%. La sensibilité et la spécificité étaient de 92% et 33%. L’IRM était positive pour 57% des patients, avec respectivement une sensibilité et une spécificité de 67% et 56%. Aucune différence significative n’a été retrouvée entre les deux méthodes d’imagerie pour la détection (p=0,63). En analyse par segment, la sensibilité était de 44% et la spécificité était de 82% pour la TEP–scanographie à la (18F)-fluorocholine. Pour l’IRM, la spécificité était de 91%.
L’IRM ou la TEP–scanographie à la (18F)-fluorocholine permet de mettre en évidence une rechute locale après curiethérapie d’un cancer de la prostate localisé. Cependant, les biopsies de confirmation sont nécessaires du fait des limites de ces deux imageries en termes de détection.
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