Early rise of glutamate-glutamine levels in mild cognitive impairment: Evidence for emerging excitotoxicity.

BACKGROUND: Use proton magnetic resonance spectroscopy (1H-MRS) non invasive technique to assess the modifications of glutamate-glutamine (Glx) and gammaaminobutyric acid (GABA) brain levels in patients reporting a cognitive complain METHODS: Posterior cingular cortex 1H-MRS spectra of 46 patients (19 male, 27 female) aged 57 to 87 years (mean : 73.32 ± 7.33 years) with a cognitive complaint were examined with a MEGA PRESS sequence at 3T, and compounds Glutamateglutamine (Glx), GABA, Creatine (Cr) and NAA were measured. From this data the metabolite ratios Glx/Cr, GABA/Cr and NAA/Cr were calculated. In addition, all patient performed the Mini Mental State Evaluation (MMSE) and 2 groups were realized with the clinical threshold of 24. RESULTS: 16 patients with MMSE 〈 24 and 30 patients with MMSE 〉 24. Significant increase of Glx/Cr in PCC of patients with MMSE 〈 24 compared to patients with MMSE 〉 24. Moreover, GABA/Cr ratio exhibited a trend for a decrease in PCC between the two groups, while they showed a significant decrease NAA/Cr ratio. CONCLUSION: Our results concerning Glx are in agreement with a physiopathological hypothesis involving a biphasic variation of glutamate levels associated with excitotoxicity, correlated with the clinical evolution of the disease. These observations suggest that MRS assessment of glutamate levels could be helpful for both diagnosis and classification of cognitive impairment in stage.

Diagnostic and Therapeutic Issues in Glioma Using Imaging Data: The Challenge of Numerical Twinning.

Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions. The significant development of digital technologies linked to high-resolution NMR exploration, coupled with the possibilities offered by AI, means that we can envisage the creation of digital twins of tumors and their host organs, thus reducing the use of physical sampling.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

Case Report: Pulmonary Leptospirosis Misdiagnosed as COVID-19.

We report the case of an 83-year-old woman with acute, febrile respiratory failure resulting from interstitial pneumonia that required high-flow oxygen therapy. This clinical picture, associated with the ongoing epidemiological situation, initially guided us toward a diagnosis of COVID-19. Based on SARS-CoV-2 reverse transcription-polymerase chain reaction negativity and the absence of anti-SARS-CoV-2 antibodies, a search for a differential diagnosis was conducted that led us to conclude a diagnosis of severe pulmonary leptospirosis This case highlights the need to engage in early discussions about differential diagnoses, including neglected tropical and subtropical diseases, during the COVID-19 era.

Refractory Auto-Immune Thrombotic Thrombocytopenic Pupura Successfully Treated With Caplacizumab.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by mechanical hemolytic anemia, profound thrombocytopenia, and neurological manifestations. Acquired auto-immune TTP, the most prevalent cause of TTP, is induced by the presence of inhibitory anti-ADAMTS13 auto-antibodies. Modern treatment of acquired TTP relies on plasma exchange, rituximab, and steroids. Caplacizumab (Cablivi®), a humanized single-variable domain immunoglobulin that targets the A1 domain of the ultra-large von Willebrand factor, inhibits the interaction between ultra-large vWFand platelets. In two clinical trials, caplacizumab, in addition to conventional treatment, shortened the delay to platelet count normalization in comparison to conventional treatment plus placebo, without increasing significantly hemorrhagic complications. Moreover, caplacizumab was associated with reduced occurrence of a secondary endpoint associating death, TTP recurrence, and major thromboembolic events. Here, we report the off-label use of caplacizumab in a 68-year-old patient with confirmed acquired TTP, severe thrombocytopenia, and generalized tonic-clonic seizures requiring mechanical ventilation and admission in the intensive care unit. Conventional treatment was rapidly started. Despite the intensification of plasma exchange treatment with twice-daily sessions, steroid continuation, and a second rituximab infusion on day 6, thrombotic microangiopathy worsened with thrombocytopenia at 21 g/L on day 8 from admission. We also considered using caplacizumab, which we could obtain and start on day 12 from admission, as it was available under a temporary authorization use in France. As soon as 12 h after caplacizumab initiation, we observed a significant increase of platelet count and improvement of other hemolytic parameters. We observed resolution of encephalopathy and complete recovery of motor paralysis, allowing us to stop mechanical ventilation on day 14. Caplacizumab was maintained for 128 days until day 139 from initial admission. The patient is going well 10 months after initial admission, without any neurological sequelae, and TTP did not relapse. To the best of our knowledge, this is the first reported use of caplacizumab in such a condition. This case report suggests that caplacizumab use may help to reduce the rate of refractory TTP episodes.

Adaptive curvature-guided image filtering for structure + texture image decomposition.

A preliminary structure + texture image decomposition is very useful for a number of digital image processing tasks, as different strategies are supposed to be employed for processing the structure and texture image components. In this paper, a new variational structure + texture image decomposition method is developed. The main ingredients of the proposed approach are: (1) using a low-pass filtered level-set curvature of the input image as a guidance image; (2) texture suppressing by minimizing a variable exponent energy, where the variable exponent is learned from the result of the curvature-guided image filtering. Numerical experiments demonstrate that the method is competitive with the current state of the art in structure + texture image decomposition. Several applications are considered.