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Abstract Background Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. Methods A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. Results The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. Conclusions The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.

Abstract Introduction Neurosarcoidosis (NS) is a systemic inflammatory granulomatous disease affecting of patients with sarcoidosis. Its diagnosis is difficult as there is no specific test for it. Because of its rarity, the management of NS has so far only been described in case series and short retrospective cohorts. The objective of this study is description of the clinical, paraclinical presentation and the therapeutic management of central nervous system (CNS) involvement in NS patients in France. Methods This multicenter, retrospective, observational study involved patients hospitalized between 2010 and 2019 with a diagnosis of sarcoidosis and CNS involvement. Results We included 118 patients (38 with isolated NS, 80 with NS associated with systemic sarcoidosis). NS was the initial presentation in 78% of patients, with cranial nerve involvement (36%), medullary symptoms (23%), and seizures (21%). Twenty‐one percent of the patients had already been diagnosed with systemic sarcoidosis. The most frequent biological abnormality was lymphopenia (62.5%), while angiotensin‐converting enzyme was increased in 21%. Meningitis was present in 45% and hyperproteinorachia in 69.5% of cases. MRI mainly revealed white matter abnormalities and leptomeningeal enhancement (34%). Corticosteroids were the most useful treatment, and immunosuppressive agents were used in steroid‐resistant patients and to limit side effects. Methotrexate, cyclophosphamide, and anti‐TNFα were also used, exhibiting good efficacy. Conclusions This cohort contributes to a better understanding of the clinical phenotype and associated imaging and biological abnormalities. Sharing of clinical, biological, and imaging data, as well as the therapeutic responses, of patients with NS helps to better understand and manage this disease that affects a small number of patients per center. A database project could be implemented in the future to enable this.

Abstract Background Infliximab is currently recommended as a third-line treatment for refractory sarcoidosis. Data in function of clinical phenotype are currently lacking. We evaluated patients’ characteristics and responses to infliximab according to their GenPhenReSa cluster. Methods We evaluated clinical and biological characteristics of patients diagnosed with sarcoidosis who received infliximab between September 2008 and April 2019 at our centre. Results Fifty-five patients (median disease duration, 87 months) received infliximab: 48 (87%) as a second- or third-line treatment, and 7 (13%) as a first-line treatment. After a median duration of 12 months, 24 (45%) and 14 (25%) patients achieved complete and partial responses, respectively, together with a significant decrease in the number of affected organs and tapering of steroid doses. All patients with neurosarcoidosis (OR 17), 90% in group 2 (ocular-cardiac-cutaneous-CNS, OR 7.4), and approximately two-thirds of those in groups 1 (abdominal organs), 4 (pulmonary-lympho-nodal), and 5 (extrapulmonary), achieved a response, whereas patients in group 3 (musculoskeletal-cutaneous) had a treatment-failure OR of 9. Infliximab could be stopped after complete remission was achieved in 7 patients: 4 relapsed after a median of 6 months. Overall, 36% of patients experienced serious adverse events, mainly infections, which led to treatment cessation in 29% of patients and caused two deaths. Conclusions Other than patients with musculoskeletal-cutaneous involvement (group 3), infliximab led to a good response for patients with CNS (group 2) and liver (group 1) organ-predominant sarcoidosis. However, it led to serious infections and merely suspended sarcoidosis, so further research on factors predictive of relapse is needed.

Acute hepatic porphyrias are inherited metabolic disorders of heme biosynthesis characterized by the accumulation of toxic intermediate metabolites responsible for disabling acute neurovisceral attacks. Givosiran is a newly approved siRNA-based treatment of acute hepatic porphyria targeting the first and rate-limiting δ-aminolevulinic acid synthase 1 (ALAS1) enzyme of heme biosynthetic pathway. We described a 72-year old patient who presented with severe inaugural neurological form of acute intermittent porphyria evolving for several years which made her eligible for givosiran administration. On initiation of treatment, the patient developed a major hyperhomocysteinemia (>400 μmol/L) which necessitated to discontinue the siRNA-based therapy. A thorough metabolic analysis in the patient suggests that hyperhomocysteinemia could be attributed to a functional deficiency of cystathionine β-synthase (CBS) enzyme induced by givosiran. Long-term treatment with vitamin B6, a cofactor of CBS, allowed to normalize homocysteinemia while givosiran treatment was maintained. We review the recently published cases of hyperhomocysteinemia in acute hepatic porphyria and its exacerbation under givosiran therapy. We also discuss the benefits of vitamin B6 supplementation in the light of hypothetic pathophysiological mechanisms responsible for hyperhomocysteinemia in these patients. Our results confirmed the importance of monitoring homocysteine metabolism and vitamin status in patients with acute intermittent porphyria in order to improve management by appropriate vitamin supplementation during givosiran treatment.

BackgroundStrong interactions between art and health are well-known. While advances in brain surgery resulted in an improved preservation of sensorimotor, visuospatial, language and cognitive functions, creative abilities received less attention. However, creativity may represent a critical issue to resume an optimal quality of life, especially in artists. Here, a unique case of sudden change in creative style in a painter who underwent glioma resection is described. This prompts to explore further creative thinking and its clinical implications in routine practice.MethodsA 36-year-old right-handed woman experienced inaugural seizures, allowing the discovery of a right frontal lesion. The patient was a professional painter and did not complain about any decline in her creativity. The preoperative neurological examination was normal.ResultsSurgery was achieved with a maximal tumor resection through a frontal lobectomy. A WHO grade II oligodendroglioma was diagnosed. A regular surveillance was performed without adjuvant oncological treatment. The patient did not exhibit postoperative functional deterioration and she returned to normal activities including painting during 15 years. Remarkably, even though her creative activity was judged by the patient herself to be rich and satisfying, her style drastically changed from surrealism and mysticism to cubism whereas she was not able to explain why.ConclusionThis is the first report of acute modification of the painting style following frontal lobectomy for a low-grade glioma, supporting that brain resective surgery may impact creativity. While neglected for many decades, this complex human ability should be evaluated more regularly in neurosurgical practice, particularly in artists.

Abstract We evaluated people living with Human Immunodeficiency Virus’ (PLWH) quality of life (QoL) and assessed whether their demographic, disease-related, socioeconomic, or behavioral characteristics were associated with poorer QoL. ANRS CO3 AQUIVIH-NA cohort participants (Nouvelle Aquitaine, France) were recruited to a cross-sectional study (2018–2020) and their QoL assessed (WHOQOL-BREF). We calculated median (Q1, Q3) QoL domain scores and assessed factors associated with poorer median QoL using bivariable and multivariable quartile regression. Of the 965 PLWH included, 98.4% were on antiretroviral therapy, 94.7% were virally-suppressed, 63.5% reported good/very good QoL. Median scores (0–100) were highest for physical (69;Q1, Q3: 56, 81) and environmental (69; 56, 75) QoL and lowest for social (56; 44, 69) and psychological (56; 44, 69) QoL. PLWH with ≥ 3 comorbidities, HIV-related stigma, or income of

Direct electrical stimulation, the transient 'lesional' method probing brain function, has been utilized in identifying the language cortex and preserving language function during epilepsy and neuro-oncological surgeries for about a century. However, comparison of functional maps of the language cortex across languages/continents based on cortical stimulation remains unclear. We conducted a retrospective multicentre study including four cohorts of direct electrical stimulation mapping from four centres across three continents, where three indigenous languages (English, French and Mandarin) are spoken. All subjects performed the two most common language tasks: number counting and picture naming during stimulation. All language sites were recorded and normalized to the same brain template. Next, Spearman's correlation analysis was performed to explore the consistency of the distributions of the language cortex across centres, a kernel density estimation to localize the peak coordinates, and a hierarchical cluster analysis was performed to detect the crucial epicenters. A total of 598 subjects with 917 speech arrest sites (complete interruption of ongoing counting) and 423 anomia sites (inability to name or misnaming) were included. Different centres presented highly consistent distribution patterns for speech arrest (Spearman's coefficient r ranged from 0.60 to 0.85, all pair-wise correlations P

Background: Neurosarcoidosis is a rare manifestation of sarcoidosis with heterogeneous presentations. Patient management is challenging due to the current lack of knowledge about the long-term disease course. Objective: To identify specific disease courses of neurosarcoidosis according to the clinical and paraclinical presentations at onset. Methods: We conducted an observational multicenter cohort study by retrospectively collecting data from the medical records of 84 patients diagnosed with definite, probable, or possible neurosarcoidosis in three tertiary referral centers in France (Nancy, Strasbourg, and Bordeaux). We collected demographic characteristics, clinical and paraclinical data at the beginning of patient management, and during follow-up under the different treatment lines. Two expert neurologists determined disease course profiles. Results: The mean follow-up was 6.6 years. Almost every patient (96.4%) received steroids at some point of their follow-up. Tumor Necrosis Factor-alpha blockers were given in 10.7% as first-line treatment and in 33.3% during follow-up. Every patient presented with a relapsing disease, often monophasic (75%) and sometimes polyphasic with the recurrence of identical manifestations (11.9%). Patients developing new neurological symptoms during follow-up were a minority (13.1%). No patients exhibited a progressive course. Patients with isolated cranial nerves injury or aseptic meningitis always exhibited a monophasic course, and 62.5–75% of them had a full recovery after first-line treatments. This proportion was 15.6% in other forms of the disease. Those with peripheral presentations were more likely to present a polyphasic course than patients with other forms of neurosarcoidosis. Spinal cord presentations were monophasic, but resulted in sequelae and exhibited poor response to first-line treatments despite frequent use of TNF-alpha blockers. Conclusion: Identification of these disease course profiles, based on the initial clinical and paraclinical presentation, could guide the clinician to select the optimal therapeutic approach and follow-up modalities for their patients with neurosarcoidosis.

IntroductionNeurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy.Methods and analysisPatients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery.Ethics and disseminationEthics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses.Clinical trial registrationClinicalTrials.gov, identifier NCT05844605.

Abstract Background To evaluate drug use (alcohol, tobacco, cannabis and other drugs) and its association with mean CD4/CD8 T cell count ratio, a marker of chronic inflammation, in virally suppressed people living with HIV-1 (PLWH) in Nouvelle Aquitaine, France. Methods A multi-centric, cross-sectional analysis was conducted in 2018–19 in the QuAliV study—ANRS CO3 AQUIVIH-NA cohort. Tobacco, alcohol, cannabis, and other drug use (poppers, cocaine, amphetamines, synthetic cathinones, GHB/GBL) were self-reported. CD4 and CD8 T cell counts and viral load measures, ± 2 years of self-report, and other characteristics were abstracted from medical records. Univariable and multivariable linear regression models, adjusted for age, sex, HIV risk group, time since HIV diagnosis, and other drug use were fit for each drug and most recent CD4/CD8 ratio. Results 660 PLWH, aged 54.7 ± 11.2, were included. 47.7% [315/660] had a CD4/CD8 ratio of

In March 1882, the Kingdom of Italy suspended diplomatic relations with the Republic of Uruguay because two Italian immigrants accused of murder, Raffaele Volpi and Vicenzo Patroni, had been tortured by the Uruguayan police. At that time, criminals and marginalized people were commonly stigmatized and persecuted by the authorities, who considered them to be blocking the political and cultural development of »modern« Uruguay. This context framed the episode. Through historical analysis of the Volpi-Patroni case, its broad press coverage and transnational impact, this article examines the complex process of social identity formation at the time of the massive arrival and inclusion of foreigners into Uruguay society in the last two decades of the 19th century.

PurposeThe management of recurrent WHO grades II–III (rGII–III) glioma is not well established. This study describes the clinical outcomes in patients who received bevacizumab as rescue treatment.MethodsIn this retrospective study, the main inclusion criteria were as follows: adult patients with histologicaly proved rGII–III glioma according 2016 WHO classification treated with bevacizumab from 2011 to 2019, T1 contrast enhancement on MRI. Efficacy was assessed using the high-grade glioma 2017 Response Assessment in Neuro-Oncology criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsEighty-one patients were included (M/F ratio: 1.7, median age at diagnosis: 38 years) among whom 46 (56.8%) had an initial diagnosis of grade II glioma. Previous treatments included at least one surgical intervention, radiotherapy (98.8%), and ≥ 2 chemotherapy lines (64.2%). After bevacizumab initiation, partial response, stable disease, and progressive disease were observed in 27.2%, 22.2%, and 50.6% of patients. The median PFS and OS were 4.9 months (95% confidence interval [CI] 3.7–6.1) and 7.6 months (95% CI 5.5–9.9). Bevacizumab severe toxicity occurred in 12.3%. Twenty-four (29.6%) patients discontinued bevacizumab without radiological progression. Oligodendroglioma and age ≥ 38 years at diagnosis were more frequent in this subgroup (odds ratio = 0.24, 95% CI 0.07–0.84, p = 0.023 and 0.36, 95% CI 0.13–0.99, p = 0.042). Ten of these 24 patients were alive at 12 months and two patients at 8 years after bevacizumab initiation, without any subsequent treatment.ConclusionBevacizumab can be an option for heavily pretreated patients with rGII–III glioma with contrast enhancement. In our study, bevacizumab displayed prolonged activity in a subgroup of patients.

The aim of this study was to identify metabolomic signatures associated with the gliomagenesis pathway (IDH-mutant or IDH-wt) and tumor grade of diffuse gliomas (DGs) according to the 2021 WHO classification on frozen samples and to evaluate the diagnostic performances of these signatures in tumor samples that are formalin-fixed and paraffin-embedded (FFPE). An untargeted metabolomic study was performed using liquid chromatography/mass spectrometry on a cohort of 213 DG samples. Logistic regression with LASSO penalization was used on the frozen samples to build classification models in order to identify IDH-mutant vs. IDH-wildtype DG and high-grade vs low-grade DG samples. 2-Hydroxyglutarate (2HG) was a metabolite of interest to predict IDH mutational status and aminoadipic acid (AAA) and guanidinoacetic acid (GAA) were significantly associated with grade. The diagnostic performances of the models were 82.6% AUC, 70.6% sensitivity and 80.4% specificity for 2HG to predict IDH status and 84.7% AUC, 78.1% sensitivity and 73.4% specificity for AAA and GAA to predict grade from FFPE samples. Thus, this study showed that AAA and GAA are two novel metabolites of interest in DG and that metabolomic data can be useful in the classification of DG, both in frozen and FFPE samples.

In implant dentistry, plaque control and oral hygiene practices are essential to limit the risk of complication and failure in the long term. All conditions around an implant in function that influence the load and pathogenicity of the microbiota are considered local risk indicators. They concern the prosthetic suprastructure design and the possibility for the patient to easily access each implant for plaque removal. Use of cemented prostheses should be limited to avoid excess cement acting as a foreign body and leading to peri-implant disease. The crown margins should be supramucosal, and the connection should be precise to avoid a gap between the implant and the suprastructure. Every implant system is characterised by a specific design, surface texture and connection type. These features may influence peri-implantitis development and progression, and the clinician should consider the risk of infection when selecting an implant. The soft-tissue conditions around the implant, the width of keratinised mucosa, and the phenotype and thickness of the mucosa are also considered major risk indicators, as the presence of any mucosal defect around an implant can increase plaque accumulation and result in tissue inflammation. The pathogenicity of the microbiota around an implant is primarily dependent on pocket depth. Deep pockets around implants should be avoided and, if present, closely monitored and/or reduced. Proximity to natural teeth presenting endodontic and/or periodontal lesions may result in implant contamination, but the influence of the type of edentulism on perio-pathogen presence is still unclear. These local conditions around an implant have a clear influence on peri-implant diseases development and progression, but there is still only limited evidence regarding their role as true risk indicators.

Abstract We aimed to estimate the prevalence of depressive disorder in people living with HIV (PLWH) and evaluate its association with non-HIV-specific and HIV-specific factors in PLWH and in PLWH compared to the general population (GP). We used cross-sectional data from the QuAliV study, conducted within the ANRS-CO3 Aquitaine-AQUIVIH-NA cohort of PLWH in Nouvelle-Aquitaine (2018–2020), and a nationally-representative survey in the GP (EHIS-ESPS, 2014–2015), we included all participants aged ≥ 18 years old who had completed the Patient Health Questionnaire-8 (PHQ-8). Depressive disorder was defined as Patient Health Questionnaire-8 score greater or equal to 10. Its association with non-HIV-specific (demographic, socio-economic, behavioral, health status), HIV-specific factors (immuno-viral markers, antiretrovirals, level of perceived HIV-stigma), and HIV-status was assessed using Poisson regression models with robust variance in women and men separately. We included 914 PLWH (683 men/231 women). More than one in five PLWH had depressive disorder. It was strongly associated with being younger and experiencing severe pain in both sexes. Unemployment in women, being single, and lack of family ties in men were also associated with depressive disorder. More than 30% of our sample reported HIV-stigma, with a dose–response relationship between level of perceived HIV-stigma and depressive disorder. The crude prevalence of depressive disorder was 2.49 (95%CI 1.92–3.22) and 4.20 (95%CI 3.48–5.05) times higher in women and men living with HIV respectively compared to GP counterparts and 1.46 (95%CI 1.09–1.95) and 2.45 (95%CI 1.93–3.09) times higher after adjustment for non-HIV specific factors. The adjusted prevalence ratio of depressive disorder was not significantly different in HIV-stigma free women, but remained twice as high in HIV-stigma free men. The prevalence of depressive disorder compared to the GP tended to decrease with age in PLWH. Excess depressive disorder remains a major concern in PLWH. Our findings reaffirm the importance of regular screening. Tackling social inequalities and HIV-stigma should be prioritized to ensure that PLWH achieve good mental as well as physical health outcomes.

Abstract Background Lyme borreliosis is the most prevalent arthropod-borne infection in the Northern Hemisphere. In Europe, Borrelia afzelii is predominantly involved in cutaneous manifestations, Borrelia garinii and Borrelia bavariensis in neurological manifestations, and Borrelia burgdorferi sensu stricto in articular ones. Liver impairement is not classical in Lyme borreliosis. Diagnosis is currently mainly based on serological testing, and is challenging in immunocompromised patients. Case presentation We report the first case of B. garinii infection revealed by liver involvement in an immunocompromised man. A 73-year-old man with marginal zone lymphoma, treated with bendamustine and rituximab, developed intermittent fever and inflammatory syndrome. Microbial investigations were all negative and FDG-PET showed complete remission of the lymphoma. Three months later, liver biopsy was performed and histology revealed spirochetes-like bacteria. Microbial diagnosis was performed by 16S rDNA sequencing, flagellin (flaB) gene sequencing and multi-locus sequence typing and identified B. garinii. The patient recovered successfully after a three weeks course of antibiotics. Diagnosis was challenging because Borrelia hepatic involvement is unusual and no erythema migrans nor tick bite were notified. Conclusion This case highlights that unexplained fever and inflammatory syndrome in immunocompromised patients warrants specific investigations to identify bacteria such as spirochetes.