University of Limoges
  • Limoges, France
Recent publications
Background While malaria morbidity and mortality have declined since 2000, viral central nervous system infections appear to be an important, underestimated cause of coma in malaria-endemic Eastern Africa. We aimed to describe the etiology of non-traumatic comas in young children in Benin, as well as their management and early outcomes, and to identify factors associated with death. Methods From March to November 2018, we enrolled all HIV-negative children aged between 2 and 6 years, with a Blantyre Coma Score ≤ 2, in this prospective observational study. Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol, including blood cultures, malaria diagnostics, and cerebrospinal fluid analysis using multiplex PCR. To determine factors associated with death, univariate and multivariate analyses were performed. Results From 3244 admissions, 84 children were included: malaria was diagnosed in 78, eight of whom had a viral or bacterial co-infection. Six children had a non-malarial infection or no identified cause. The mortality rate was 29.8% (25/84), with 20 children dying in the first 24 h. Co-infected children appeared to have a poorer prognosis. Of the 76 children who consulted a healthcare professional before admission, only 5 were prescribed adequate antimalarial oral therapy. Predictors of early death were jaundice or increased bilirubin [odd ratio ( OR )= 8.6; 95% confidential interval ( CI ): 2.03–36.1] and lactate > 5 mmol/L ( OR = 5.1; 95% CI : 1.49–17.30). Antibiotic use before admission ( OR = 0.1; 95% CI : 0.02–0.85) and vaccination against yellow fever ( OR = 0.2, 95% CI : 0.05–0.79) protected against mortality. Conclusions Infections were found in all children who died, and cerebral malaria was by far the most common cause of non-traumatic coma. Missed opportunities to receive early effective antimalarial treatment were common. Other central nervous system infections must be considered in their management. Some factors that proved to be protective against early death were unexpected.
Here we present the ability of Nd ³⁺ -doped zinc-phosphate glasses to be shaped into rectangular core fibers. At first, the physico-chemical properties of the developed P 2 O 5 -based materials are investigated for different concentrations of neodymium oxide and core and cladding glass compositions are selected for further fiber development. A modified stack-and-draw technique is used to produce multimode large rectangular-core optical fibers. Self-guided nonlinear effects acting as spatial beam reshaping processes occurring in these newly-developed photonic structures lead to the generation of spectral broadenings in the visible and near-infrared spectral domains. Graphic Abstract
Objectives To identify the factors related to the presence of occult metastases before salvage total laryngectomy (STL) in rcN0 patients and to propose an algorithm to identify patients who do not require neck dissection (ND). Patients and methods This multicentric retrospective study included five centers with recruitment from 2008 to 2018. Inclusion criteria were: i) having been treated for laryngeal squamous cell carcinoma in first intention by radiotherapy (either alone or potentiated or preceded by induction chemotherapy), ii) having received STL with or without ND, iii) having an rcN0 neck at the time of STL. Results 120 patients met the inclusion criteria. The overall rate of occult metastases was 9.1 %. The rate was significantly higher in patients with an initial positive cN+ lymph node status (p < 0.005) and in advanced stages with rcT3-T4 lesions at recurrence (p < 0.005). Patients with occult metastases recurred earlier than those without (p = 0.002). The overall survival of patients was the same with or without ND (p = 0.16). There were significantly more healing complications requiring revision surgery in the group with ND than in the group without (p = 0.048). Conclusion ND does not confer a net survival benefit and is associated with significant complications. Patients without initial lymph node metastases who are rcT1-T2 at recurrence or rcT3-T4 with a recurrence period of more than 12 months could benefit from STL without ND. This decisional algorithm, which needs to be validated, would help avoid 58 % of ND procedures and their proven morbidity. Discipline Head and neck surgery.
Background and purpose To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS). Methods Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals’ adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0–2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores. Results A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52–0.89] and aOR 0.66; 95%CI [0.5–0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20–0.79]). Conclusion Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals.
Here we explore the manufacturing of niobium-rich borophosphate glasses into fibers with optical quality. Glass preforms of composition [(100-x) (0.95 NaPO3 + 0.05 Na2B4O7) - x Nb2O5] with x = 37, 38, 39, 40 were synthetized and thermally drawn. Viscosity measurements performed in the softening point range show that the optical fiber drawing temperature gradually increases with the amount of niobium oxide. X-ray diffraction and Raman structural analysis performed post drawing demonstrate that the BPN glass with 39% Nb2O5 represents the upper limit for fiber drawing under oxygen. Subsequently, preform quenching protocol was optimized to mitigate the density fluctuations within the glass matrix related to convection flows and compare with the conventional cast-in-mold method. Optical transmission and shadowscopy imaging highlight the improvement in the optical quality of the glasses produced following this new protocol. This observation is confirmed by cut back loss measurements which show a decreasing in the attenuation from 6.04 dB/m to 3.19 dB/m between the two methods. One believes the manufacturing of niobium rich borophosphate fibers with improved optical quality highlights their potential to be used as near-infrared highly nonlinear waveguide devices.
Background Tonsil surgery causes significant and challenging postoperative pain. The Analgesia Nociception Index (ANI) and videopupillometry are two techniques of interest to monitor nociception in adults and may predict postoperative morphine requirements. We hypothesised that these techniques could predict the need for morphine after tonsillectomy in children. The main objective was to assess the prognostic significance of ANI and videopupillometry, measured at the end of surgery, on morphine consumption determined by a Face, Legs, Activity, Cry, Consolability (FLACC) scale score >3 in the Post Anesthesia Care Unit (PACU). Methods A single-centre, prospective, interventional study evaluating children between 2 and 7 yr old undergoing tonsil surgery was performed. ANI and videopupillometry with tetanic stimulation were measured under general anaesthesia 4 min after the end of the surgical procedure. Each child was evaluated every 10 min by a nurse using the FLACC scale in the PACU and blinded to the measurements performed in the operating theatre. Results Eighty-nine children were analysed and 39 (44%) received morphine in the PACU. Neither ANI values nor videopupillometry values were predictive of postoperative morphine consumption (areas under the receiver operating characteristic curve 0.54, 95% confidence interval [CI; 0.42–0.65], and P=0.57; and 0.52, 95% CI [0.41–0.63], and P=0.69, respectively). Neither ANI values nor videopupillometry values were correlated to the maximum FLACC scale score in the PACU with ρ=0.04 (P=0.71) and ρ=0.06 (P=0.57), respectively. Conclusions Neither ANI nor videopupillometry performed at the end of surgery can predict morphine consumption in the PACU in children undergoing tonsillectomy.
Regulation of gene expression is a key factor influencing the success of antimicrobial resistance determinants. A variety of determinants conferring resistance against aminoglycosides (Ag) are commonly found in clinically relevant bacteria, but whether their expression is regulated or not is controversial. The expression of several Ag resistance genes has been reported to be controlled by a riboswitch mechanism encoded in a conserved sequence. Yet this sequence corresponds to the integration site of an integron, a genetic platform that recruits genes of different functions, making the presence of such a riboswitch counterintuitive. We provide, for the first time, experimental evidence against the existence of such Ag-sensing riboswitch. We first tried to reproduce the induction of the well characterized aacA5 gene using its native genetic environment, but were unsuccessful. We then broadened our approach and analyzed the inducibility of all AgR genes encoded in integrons against a variety of antibiotics. We could not observe biologically relevant induction rates for any gene in the presence of several aminoglycosides. Instead, unrelated antibiotics produced mild but consistently higher increases in expression, that were the result of pleiotropic effects. Our findings rule out the riboswitch control of aminoglycoside resistance genes in integrons.
Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Co-administration of nirmatrelvir/ritonavir with immunosuppressant drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. While a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here we provide some general recommendations for therapeutic drug monitoring (TDM) of ISDs and dosing recommendations when co-administered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day-1, while cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.
Background Cases of Toxoplasma reactivation or more severe primary infection have been reported in patients receiving immunosuppressive (IS) treatment for autoimmune diseases (AID). The purpose of this study was to describe features of toxoplasmosis occurring in patients with AID treated by IS therapy, excluded HIV-positive and transplant patients. Methods A multicenter descriptive study was conducted using data from the French National Reference Center for Toxoplasmosis (NRCT) that received DNA extracts or strains isolated from patients, associated with clinical data. Other cases were retrieved through a questionnaire sent to all French parasitology and internal medicine departments. Furthermore, a systematic literature review was conducted. Results 61 cases were collected: 25 retrieved by the NRCT and by a call for observations and 36 from a literature review. Half of the cases were attributed to reactivation (50.9%), and most of cases (49.2%) were cerebral toxoplasmosis. The most common associated AID were rheumatoid arthritis (28%) and most frequent treatments were antimetabolites (44.3%). Corticosteroids were involved in 60.7% of cases. Patients had a favorable outcome (50.8%) but nine did not survive. For 12 cases, a successful Toxoplasma strain characterization suggested the possible role of this parasitic factor in ocular cases. Conclusion Although this remains a rare condition, clinicians should be aware for the management of patients and for the choice of IS treatment.
Optical rogue waves have been extensively studied in the past two decades. However, observations of multidimensional extreme wave events remain surprisingly scarce. In this work we present the experimental demonstration of the spontaneous generation of spatially localized two-dimensional beams in a quadratic nonlinear crystal, which are composed by twin components at the fundamental and the second-harmonic frequencies. These localized spots of light emerge from a wide background beam, and eventually disappear as the laser beam intensity is progressively increased. Optical rogue waves are the optical counterpart of sudden and dramatic oceanic wave formations the underlying physics of which are thought to be connected with solitons. Here, the authors report the observation of a 2D spatial twin spotlight beam in anisotropic crystals with quadratic nonlinearity, that spontaneously appears and disappears as a function of laser beam in intensity.
Objective Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure. Study design We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model. Results Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year ( P < 0.05). Neither EA type nor surgical treatment was associated with growth failure. Conclusion Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.
Introduction Vancomycin is one of the antibiotics most used in neonates. Continuous infusion has many advantages over intermittent infusions, but no consensus has been achieved regarding the optimal initial dose. The objectives of this study were: to develop a Machine learning (ML) algorithm based on pharmacokinetic profiles obtained by Monte Carlo simulations using a population pharmacokinetic model (POPPK) from the literature, in order to derive the best vancomycin initial dose in preterm and term neonates, and to compare ML performances with those of an literature equation (LE) derived from a POPPK previously published. Materials and methods The parameters of a previously published POPPK model of vancomycin in children and neonates were used in the mrgsolve R package to simulate 1900 PK profiles. ML algorithms were developed from these simulations using Xgboost, GLMNET and MARS in parallel, benchmarked and used to calculate the ML first dose. Performances were evaluated in a second simulation set and in an external set of 82 real patients and compared to those of a LE. Results The Xgboost algorithm yielded numerically best performances and target attainment rates: 46.9% in the second simulation set of 400–600 AUC/MIC ratio vs. 41.4% for the LE model (p = 0.0018); and 35.3% vs. 28% in real patients (p = 0.401), respectively). The Xgboost model resulted in less AUC/MIC > 600, thus decreasing the risk of nephrotoxicity. Conclusion The Xgboost algorithm developed to estimate the initial dose of vancomycin in term or preterm infants has better performances than a previous validated LE and should be evaluated prospectively.
Background Non-communicable diseases (NCDs) account for an estimated 71% of all global deaths annually and nearly 80% of these deaths occur in low- and middle-income countries. This study aimed to assess the readiness of existing healthcare systems at different levels of health care in delivering NCDs management and prevention services in Kenya. Methods A cross-sectional survey of 258 facilities was conducted between June 2019 and December 2020 using multistage sampling, examining facility readiness based on the availability of indicators such as equipment, diagnostic capacity, medicines and commodities, trained staff and guidelines for NCDs management. Readiness scores were calculated as the mean availability of tracer items expressed as a percentage and a cut-off threshold of ≥ 70% was used to classify facilities as “ready” to manage NCDs. Descriptive and bivariate analyses were performed to assess the readiness of facilities by type, level, and location settings. Logistic regressions were used to identify factors associated with the readiness of facilities to provide disease-specific services. Results Of the surveyed facilities, 93.8% offered chronic respiratory disease (CRD) diagnosis and/or management services, 82.2% diabetes mellitus, 65.1% cardiovascular disease (CVD), and only 24.4% cervical cancer screening services. The mean readiness scores for diabetes mellitus (71%; 95% CI: 67–74) and CVD (69%; 95% CI: 66–72) were relatively high. Although CRD services were reportedly the most widely available, its mean readiness score was low (48%; 95% CI: 45–50). The majority of facilities offering cervical cancer services had all the necessary tracer items available to provide these services. Modeling results revealed that private facilities were more likely to be “ready” to offer NCDs services than public facilities. Similarly, hospitals were more likely “ready” to provide NCDs services than primary health facilities. These disparities in service readiness extended to the regional and urban/rural divide. Conclusions Important gaps in the current readiness of facilities to manage NCDs in Kenya at different levels of health care were revealed, showing variations by disease and healthcare facility type. A collective approach is therefore needed to bridge the gap between resource availability and population healthcare needs.
Background Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference—Individual Participant Data Collaboration. Methods One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. Results We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P< 0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P <0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P <0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs). Conclusions Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: CRD42015031227.
Objective Stroke caused by giant cell arteritis (GCA) is a rare but devastating condition and early recognition is of critical importance. The features of GCA-related stroke were compared with those of GCA without stroke and atherosclerosis-related or embolic stroke with the aim of more readily diagnosing GCA. Methods The study group consisted of 19 patients who experienced GCA-related strokes within an inception cohort (1982-2021) of GCA from the internal medicine department, and the control groups each consisted of 541 GCA patients without a stroke and 40 consecutive patients > 50 years of age with usual first ever stroke from the neurology department of a French university hospital. Clinical, laboratory, and imaging findings associated with GCA related-stroke were determined using logistic regression analyses. Early survival curves were estimated using the Kaplan-Meier method and compared using the log rank test. Results Amongst 560 patients included in the inception cohort, 19 (3.4%) developed GCA-related stroke. GCA-related stroke patients had more comorbid conditions (p = 0.03) and aortitis on imaging (p = 0.02), but less headache (p < 0.01) and scalp tenderness (p = 0.01). Multivariate logistic regression analysis showed that absence of involvement of the anterior circulation (OR = 0.1 – CI: 0.01-0.5), external carotid ultrasound (ECU) abnormalities (OR = 8.1 – CI: 1.3-73.9), and C-reactive protein (CRP) levels > 3 mg/dL (OR = 15.4 – CI: 1.9-197.1) were independently associated with GCA-related stroke. Early survival of GCA-related stroke patients was significantly decreased compared with control stroke patients (p = 0.02) and GCA patients without stroke (p < 0.001). Conclusions The location of stroke and assessment of ECU results and CRP level could help improve the prognosis of GCA-related stroke by bringing this condition to the clinician's attention more quickly, thus shortening diagnostic delay.
The present study aimed to determine the impact of arbuscular mycorrhizal fungi (AMF) on soil and young olive plants irrigated for one year with saline treated wastewater (TWW). One-year-old olive plants were inoculated with different AMF: (i) Glomus deserticola; (ii) Gigaspora margarita and (iii) combination of G. deserticola and G. margarita. Changes were observed in the soil chemical characteristics, in particular a significant increase in the electrical conductivity and an accumulation of Na⁺ and Cl⁻. Consequently, compared to the control treatment, the Na⁺ and Cl⁻ contents of young olive plants irrigated with TWW increased by 12 and 133% in the leaves and by 98 and 106% in the roots, respectively. Moreover, an increase in the antioxidant enzyme activities, malondialdehyde and H2O2 contents, and electrolyte leakage rate was observed. Interestingly, roots and leaves of olive plants inoculated with AMF and irrigated with TWW showed a lower Na⁺ and Cl⁻content, and a higher macro- and micro-nutrient content, compared to uninoculated plants. The decrease of Na⁺ and Cl⁻ contents in olive plants inoculated with both G. deserticola and G. margarita was about 24 and 43% in the leaves, and about 30 and 39% in the roots, respectively. Furthermore, the AMF symbiosis enhanced the antioxidant enzymes activities (CAT and APX) and reduced the malondialdehyde and H2O2 contents.
This paper presents a major reformulation of a widely used solution for computing the exact Euclidean distance transform of n-dimensional discrete binary shapes. Initially proposed by Hirata, the original algorithm is linear in time, separable, and easy to implement. Furthermore, it accounts for the fastest existing solutions, leading to its widespread use in the state of the art, especially in real-time applications. In particular, we focus on the second step of this algorithm, where the lower envelope of a set of parabolas has to be computed. By leveraging the discrete nature of images, we show that some of those parabolas can be merged into line segments. It reduces the computational cost of the algorithm by about 20% in most practical cases, while maintaining its exactness. To evaluate the proposed improvement on different cases, two state-of-the art benchmarks are implemented and discussed.
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2,278 members
Barbara Bessette
  • Département Sciences du Vivant
Aurélien Mercier
  • UMR INSERM 1094 Neuroépidémiologie Tropicale
Achille Tchalla
  • Geriatric Medicine Department
Patrick Legembre
  • Faculté de Médecine
Amandine Magnaudeix
  • IRCER (Institut de Recherche sur les Céramiques) - UMR CNRS 7315
Information
Address
33 rue François Mitterrand, 87032 , Limoges, France
Head of institution
Alain Célérier
Website
http://www.unilim.fr/
Phone
+33 (0)5 55 14 91 00