Search

Background: Despite its potentially significant functional and emotional impact, acalculia is still too rarely assessed and managed by speech and language therapists. Research on the rehabilitation of numerical transcoding remains scarce in the literature and, despite positive results, presents a low level of evidence. Aims: The present study aims to evaluate the effectiveness of a targeted rehabilitation of numerical transcoding in two patients suffering from a chronic secondary acalculia. Methods & Procedures: Two post-brain injury females with secondary acalculia took part in a single-case experimental design with multiple baseline across subjects according to a three-phase experimental protocol: baseline involving global cognitive rehabilitation (5-7 measurements with randomized sequential introduction); targeted intervention (10 measurements); follow-up (2 immediate measurements and 1 month after the end of the intervention). Repeated outcome measures consisted of six lists composed of numbers of equivalent difficulty that were used alternately to assess numerical transcoding. We used a reverse digit span as a control measure to assess the specificity of the intervention. Rehabilitation lasted 5 weeks and consisted of errorless learning with colour cues, tables and number-words cards. Outcomes & Results: During baseline period involving global cognitive rehabilitation, transcoding scores remained unchanged. In contrast, there was a significant improvement in scores for both patients during the intervention phase targeting transcoding and maintenance of benefits 1-month post-intervention. Conclusions & Implications: This study demonstrates that a specific rehabilitation targeting numerical transcoding following chronic secondary acalculia can be effective in improving transcoding skills.

Abstract The cultivation of grapevines has spanned millennia, leading to thousands of varieties through exchanges, mutations, and crosses between genotypes, as well probably as gene flow from wild populations. These varieties are typically categorized by regional origin and primary use, either for wine production or fruit consumption. France, within the Western European group, hosts many of the world’s renowned wine grape varieties. However, the historical development of cultivated grapevines in France and in the world remains poorly understood. This study applies morphometry on 19,377 charred and waterlogged archaeological grape pips to investigate the evolutionary history of grapevine in France over the last 10,000 years. The study compares seed outlines and lengths, corrected for taphonomic distortions, with a reference collection of 80 wild and 466 modern domestic grapevine accessions. Findings reveal a shift from wild grapevine exploitation to the expansion of domestic varieties around 600–500 BCE, coinciding with Mediterranean cultural influences and the introduction of eastern grape types. The identification of the East-Table group, a group of varieties of eastern origin for fruit consumption, indicates that grapes were also grown for food, especially in Mediterranean regions and near urban areas, alongside wine production. Early French viticulture featured a notable presence of Western European wine-type grapevines. The abundance of pips with wild-like morphology suggests early cultivation involved plants at an initial domestication stage and gene flow between introduced and wild grapevines. As viticulture spread northward, wild and Eastern morphotypes declined, leading to the dominance of Western European wine types in inner France during the Middle Ages.

Summary: Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). Methods: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.Cg-Tg(SOD1∗G93A)1Gur/J). The BSCB was disrupted using a 1 MHz ultrasound transducer coupled to the spinal cord, with and without injection of insulin-like growth factor 1 (IGF1), a neurotrophic factor that has previously shown efficacy in ALS models. Findings: Results in wild-type (WT) animals demonstrated that the BSCB can be safely disrupted and IGF1 concentrations significantly enhanced after a single session of transient BSCB disruption (176 ± 32 μg/g vs. 0.16 ± 0.008 μg/g, p

Abstract Background Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. Methods This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. Results Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0–26.0), 9.0 (5.0–17.0), 7.5 (5.0–14.0), 8.0 (5.0–12.5) and 8.0 (5.0–12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8–73.3), 60.0 (54.0–65.0), 60.0 (50.3–53.0), 59.0 (50.0–63.0) and 58.0 (50.0–62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. Conclusion This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs.

Abstract Background Thoracic disc herniation is relatively uncommon, accounting for less than 1% of all spinal herniations. Although most often asymptomatic, they may represent a rare cause of spinal cord ischemia. Case report We report the case of a healthy 43-year-old North African male who presented with a Brown-Sequard syndrome revealing a spinal cord ischemia caused by a thoracic disc extrusion. The initial MRI revealed a calcified disc extrusion at the level of T5-T6 without significant spinal cord compression or signal abnormality. A pattern consistent with a medullary ischemia only appeared 48 h later. The patient was treated conservatively with Aspirin and Heparin, which were discontinued later because of a negative cardiovascular work-up. The calcified disc extrusion, which was later recognized as the cause of the ischemia, decreased spontaneously over time and the patient recovered within a few months. Conclusions Our case highlights the challenge in diagnosing and managing this uncommon condition. We propose a literature review showing the different therapeutic strategies and their corresponding clinical outcomes.

Abstract Background Drug consumption rooms (DCRs) have been developed in cities with open drug scenes, with the aim to reduce drug-related harm. In Lyon, France's second-largest city, there is no distinct drug use area, which raised doubts regarding the need for a DCR. Methods We conducted a face-to-face survey of 264 people who use drugs (PWUDs), recruited in harm reduction or addiction treatment centers, in the streets or in squats. We assess their willingness to use a DCR, and we collected sociodemographic and medical features. Bivariable comparisons and analyses adjusted for sociodemographic parameters explored the association between willing to use a DCR and other variables, thus providing crude (ORs) and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results In total, 193 (73.1%) PWUDs accepted to participate (mean age 38.5 ± 9.3 years; 80.3% men). Among them, 64.2% declared willing to use a DCR. Being treatment-seeker (aOR 0.20, 95% CI [0.08–0.51]; p

Abstract Background Movement sonification, the use of real-time auditory feedback linked to movement parameters, have been proposed to support rehabilitation. Nevertheless, if promising results have been reported, the effect of the type of sound used has not been studied systematically. The aim of this study was to investigate in a single session the effect of different types of sonification both quantitatively and qualitatively on patients with acquired brain lesions and healthy participants. Methods An experimental setup enabling arm sonification was developed using three different categories of sonification (direct sound modulation, musical interaction, and soundscape). Simple moving forward movements performed while sliding on a table with both arms were investigated with all participants. Quantitative analysis on the movement timing were performed considering various parameters (sound condition, affected arm and dominance, sonification categories). Qualitative analysis of semi-structured interviews were also conducted, as well as neuropsychological evaluation of music perception. Results For both the patient and healthy groups (15 participants each), average duration for performing the arm movement is significantly longer with sonification compared to the no-sound condition (p

Abstract Background Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia–reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. Methods HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. Discussion We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing. Trial registration ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.

Background: Acquired brain injury (ABI), especially to the right hemisphere, can result in difficulty using or understanding prosodic contours in speech. Prosody is used to convey emotional connotation or linguistic intent and includes pitch, loudness, rate, and voice quality. A disorder in the comprehension or production of prosody is known as aprosodia; despite the communication disability caused by prosodic disorders, the assessment and treatment of aprosodia following ABI has received scant attention. Aims: The aim of this scoping review is to gather and synthesise useful knowledge on aprosodia and provide therapists with an exhaustive document in order to guide clinical decision-making encouraging active identification and treatment of this disorder. Methods & Procedures: This scoping review, conducted in accordance with PRISMA-ScR guidelines, investigated the existing literature concerning the assessment and treatments of linguistic and affective aprosodia in adult patients after ABI. A systematic search in four electronic databases (PubMed, CINAHL, Web of Science, ScienceDirect) was conducted for articles written in English, French, or Italian published between 1970 and 2020. After all evaluative criteria were applied, 15 articles were included for final review. Outcomes & Results: Results show the presence of six assessment tools for affective aprosodia and five evaluation tools targeting affective and linguistic prosody. Assessment of aprosodia is generally accomplished through acoustic and perceptual approaches. Current treatments for prosodic disorders focus on expressive aprosodia and have applied mostly two different approaches: imitative and cognitive-linguistic methods. Conclusion & Implications: Findings suggest that aprosodia can be assessed by therapists through various techniques and may be amenable to behavioural treatments. Nevertheless, although there are several assessment tools available, no one currently offers a comprehensive assessment that incorporates an ecological dimension. It therefore seems necessary to continue research in this direction. The rehabilitation of receptive prosody abilities also remains to be explored.

Abstract Background In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. Methods To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. Results An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). Conclusions We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

Summary: Bacterial infections are the most frequent precipitating event in patients with acute decompensation of cirrhosis (AD) and are associated with high mortality. Early diagnosis is challenging due to cirrhosis-related systemic inflammation. Here we investigated the potential of circulating microRNAs to diagnose bacterial infections and predict survival in cirrhotic patients with AD. High throughput profiling of circulating microRNAs was performed using the Nanostring technology in 57 AD patients and 24 patients with compensated cirrhosis (CC). Circulating miRs profiling showed that: (a) miRs differentially detected in AD vs. CC were mostly down-regulated; (b) a composite score including absolute neutrophil count, C reactive protein and miR-362-3p could diagnose bacterial infection with an excellent performance (AUC of 0.825 [95% CI = 0.671–0.980; p

Abstract Background Fluid overload is associated with worse outcome in critically ill patients requiring continuous renal replacement therapy (CRRT). Net ultrafiltration (UFNET) allows precise control of the fluid removal but is frequently ceased due to hemodynamic instability episodes. However, approximately 50% of the hemodynamic instability episodes in ICU patients treated with CRRT are not associated with preload dependence (i.e., are not related to a decrease in cardiac preload), suggesting that volume removal is not responsible for these episodes of hemodynamic impairment. The use of advanced hemodynamic monitoring, comprising continuous cardiac output monitoring to repeatedly assess preload dependency, could allow securing UFNET to allow fluid balance control and prevent fluid overload. Methods The GO NEUTRAL trial is a multicenter, open-labeled, randomized, controlled, superiority trial with parallel groups and balanced randomization with a 1:1 ratio. The trial will enroll adult patients with acute circulatory failure treated with vasopressors and severe acute kidney injury requiring CRRT who already have been equipped with a continuous cardiac output monitoring device. After informed consent, patients will be randomized into two groups. The control group will receive protocolized fluid removal with an UFNET rate set to 0–25 ml h−1 between inclusion and H72 of inclusion. The intervention group will be treated with an UFNET rate set on the CRRT of at least 100 ml h−1 between inclusion and H72 of inclusion if hemodynamically tolerated based on a protocolized hemodynamic protocol aiming to adjust UFNET based on cardiac output, arterial lactate concentration, and preload dependence assessment by postural maneuvers, performed regularly during nursing rounds, and in case of a hemodynamic instability episode. The primary outcome of the study will be the cumulative fluid balance between inclusion and H72 of inclusion. Randomization will be generated using random block sizes and stratified based on fluid overload status at inclusion. The main outcome will be analyzed in the modified intention-to-treat population, defined as all alive patients at H72 of inclusion, based on their initial allocation group. Discussion We present in the present protocol all study procedures in regard to the achievement of the GO NEUTRAL trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial result report. Enrollment of patients in the GO NEUTRAL trial has started on June 31, 2021, and is ongoing. Trial registration ClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.

Classification and risk-stratification for Acute Myeloid Leukemia (AML) at diagnosis are primarily based on cytogenetics and only a few gene mutations. Here, the authors study the genomic landscape of 3653 AML patients and characterize 16 non-overlapping molecular subgroups of clinical relevance for disease classification and risk prognostication.

Abstract Background Successful pain management after outpatient surgery requires proper education leading to correct decisions on the analgesics use at home. Despite different strategies adopted, up to ½ of patients receive little or no information about the treatment of postoperative pain, 1/3 of them are not able to follow postoperative analgesia instructions. This leads to higher rates of unmet needs in pain treatment, post-discharge emergency calls, and readmissions. Structured educational interventions using psychological empowering techniques may improve postoperative pain management. We hypothesize that preoperative education on use of an improved pain scale to make correct pain management decisions will improve the quality of post-operative pain management at home and reduce analgesics-related side effects. Methods A total of 414 patients scheduled for an outpatient orthopedic surgery (knee/shoulder arthroscopic interventions) are included in this randomized (1:1) controlled trial. Patients in the control arm receive standard information on post-discharge pain management. Patients in the experimental arm receive structured educational intervention based on the rational perception of postoperative pain and discomfort (anchoring and improved pain scale), and the proper use of analgesics. There is no difference in post-discharge analgesics regimen in both arms. Patients are followed for 30 days post-discharge, with the primary outcome expressed as total pain relief score at 5 days. Secondary outcomes include the incidence of severe pain during 30 days, changes in sleep quality (Pittsburg Sleep Quality Assessment), and patients’ perception of postoperative pain management assessed with the International Pain Outcomes questionnaire at day 30 post-discharge. Discussion The developed intervention, based on an improved pain scale, offers the advantages of being non-surgery-specific, is easily administered in a short amount of time, and can be delivered individually or in-group, by physicians or nurses. Trial registration ClinicalTrials.gov NCT03754699 . Registered on November 27, 2018.

Abstract Background The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle‐secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology. Methods Sporadic ALS patients were confirmed to be ALS according to El Escorial criteria and were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS‐R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n = 27) or deltoids of aged‐matched healthy subjects (n = 30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RT‐qPCR, and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human‐derived iPSC MNs and on healthy human myotubes, with untreated cells used as controls. Results An accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy‐derived denervation‐naïve differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome‐like vesicles and disruption of RNA‐processing. Compared with vesicles from healthy control myotubes, when administered to healthy MNs the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA‐processing proteins. The RNA‐processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient MNs was abolished by anti‐CD63 immuno‐blocking of vesicle uptake. Conclusions ALS muscle vesicles are shown to be toxic to MNs, which establishes the skeletal muscle as a potential source of vesicle‐mediated toxicity in ALS.

This article discusses the use of MRI imaging techniques to study the progression of ALS and related neurodegenerative disorders. The study focuses on identifying biomarkers of degeneration and understanding the underlying pathogenic mechanisms. The research involves longitudinal cervical spinal cord pathology using MRI in asymptomatic C9Orf72 first-degree relatives, as well as clinical imaging and electrophysiology to detect cortical hyperexcitability in ALS patients. The findings suggest that stable white matter atrophy may indicate a neurodevelopmental condition, while changes in fractional anisotropy could be an early marker of progressive degeneration. Further studies are needed to confirm these hypotheses and improve diagnostic and prognostic tools for ALS. [Extracted from the article]

Abstract To assess the usefulness of a theoretical postural instability discrimination index (PIth) in amyotrophic lateral sclerosis (ALS). Prospective regression analyzes were performed to identify the biomechanical determinants of postural instability unrelated to lower limb motor deficits from gait initiation factors. PIth was constructed using a logit function of biomechanical determinants. Discriminatory performance and performance differences were tested. Backward displacement of the pression center (APAamplitude) and active vertical braking of the mass center (Braking-index) were the biomechanical determinants of postural instability. PIth = − 0.13 × APAamplitude − 0.12 × Braking-index + 5.67, (P

Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition. The clinical picture is dominated by upper and lower motor neuron degeneration, but extra-motor pathology is increasingly recognized, including cerebellar pathology. Post-mortem and neuroimaging studies primarily focus on the characterization of supratentorial disease, despite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis. Cardinal clinical features of amyotrophic lateral sclerosis, such as dysarthria, dysphagia, cognitive and behavioral deficits, saccade abnormalities, gait impairment, respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology. This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral sclerosis. Structural imaging studies consistently capture cerebellar grey matter volume reductions, diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alterations and functional imaging studies commonly report increased functional connectivity with supratentorial regions. Increased functional connectivity is commonly interpreted as evidence of neuroplasticity representing compensatory processes despite the lack of post-mortem validation. There is a scarcity of post-mortem studies focusing on cerebellar alterations, but these detect pTDP-43 in cerebellar nuclei. Cerebellar pathology is an overlooked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms, widespread connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.

The availability of patient cohorts with several types of omics data opens new perspectives for exploring the disease's underlying biological processes and developing predictive models. It also comes with new challenges in computational biology in terms of integrating high-dimensional and heterogeneous data in a fashion that captures the interrelationships between multiple genes and their functions. Deep learning methods offer promising perspectives for integrating multi-omics data. In this paper, we review the existing integration strategies based on autoencoders and propose a new customizable one whose principle relies on a two-phase approach. In the first phase, we adapt the training to each data source independently before learning cross-modality interactions in the second phase. By taking into account each source's singularity, we show that this approach succeeds at taking advantage of all the sources more efficiently than other strategies. Moreover, by adapting our architecture to the computation of Shapley additive explanations, our model can provide interpretable results in a multi-source setting. Using multiple omics sources from different TCGA cohorts, we demonstrate the performance of the proposed method for cancer on test cases for several tasks, such as the classification of tumor types and breast cancer subtypes, as well as survival outcome prediction. We show through our experiments the great performances of our architecture on seven different datasets with various sizes and provide some interpretations of the results obtained. Our code is available on (https://github.com/HakimBenkirane/CustOmics).