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Réhabilitation orale conservatrice sous anesthésie générale en médecine bucco-dentaire pédiatrique : une étude rétrospective des indications selon la typologie des patients
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A Low-Gluten Diet Reduces the Abundance of Potentially Beneficial Bacteria in Healthy Adult Gut Microbiota
No full textInternational audienceBackground/Objectives: An increasing number of apparently healthy individuals are adhering to a gluten-free lifestyle without any underlying medical indications, although the evidence for the health benefits in these individuals remains unclear. Although it has already been shown that a low- or gluten-free diet alters the gut microbiota, few studies have examined the effects of this diet on healthy subjects. Therefore, our aim was to evaluate whether and how a prolonged low-gluten diet impacts gut microbiota composition and function in healthy adults, bearing in mind its intimate link to the host’s health. Methods: Forty healthy volunteers habitually consuming a gluten-containing diet (HGD, high-gluten diet) were included in a randomised control trial consisting of two successive 8-week dietary intervention periods on a low-gluten diet (LGD). After each 8-week period, gut microbiota composition was assessed by 16S rRNA gene sequencing, molecular quantification by qPCR, and a cultural approach, while its metabolic capacity was evaluated through measuring faecal fermentative metabolites by 1H NMR. Results: A prolonged period of LGD for 16 weeks reduced gut microbiota richness and decreased the relative abundance of bacterial species with previously reported potential health benefits such as Akkermansia muciniphila and Bifidobacterium sp. A decrease in certain plant cell wall polysaccharide-degrading species was also observed. While there was no major modification affecting the main short-chain fatty acid profiles, the concentration of the intermediate metabolite, ethanol, was increased in faecal samples. Conclusions: A 16-week LGD significantly altered both composition and metabolic production of the gut microbiota in healthy individuals, towards a more dysbiotic profile previously linked to adverse effects on the host’s health. Therefore, the evaluation of longer-term LDG would consolidate these results and enable a more in-depth examination of its impact on the host’s physiology, immunity, and metabolism
Lipidomic profile analysis reveals new links to sarcopenic obesity criteria in the obesar cohort
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Pro-inflammatory processes and metabolic syndrome: combined risk of resistance to treatment in patients with schizophrenia from the FACE-SZ cohort
No full textInternational audienceSchizophrenia (SZ) is characterized by a variable clinical expression and course peppered/hampered by severe complications. In particular, resistance to treatment (overall-TRS, treatment resistant SZ including UTRS, ultra-TRS) and metabolic syndrome (MetS) are highly prevalent, and both demonstrated to be underpinned, at least partly, by pro-inflammatory processes. Given that such processes also underlie SZ per se , we hypothesized that potential inter-twinning between SZ-and MetS-related inflammatory processes may exert a combined effect on the risk of having overall-TRS/UTRS. A total of 419 outpatients with SZ underwent clinical assessments and blood sample collection. Using the values of circulating levels of eleven cytokines, we built a ratio between pro-and anti-inflammatory components respectively corresponding to the immunoinflammatory response system (IRS) and the compensatory immunoregulatory reflex system (CIRS) which overall reflect the underlying in-flammatory status. Such ratios allowed to categorize the patients according to Inflammation and MetS on four categories as follow: symbolscript symbolscript symbolscript and Inflam-mation(-)MetS(-). Multivariate logistic regression analysis showed that the combination of inflammation and MetS modulate the risk of having the overall-TRS symbolscript symbolscript 95 %CI [1.04-5.00], p symbolscript 0.039 and symbolscript symbolscript 95 % CI [1.76-11.97], p symbolscript 0.002 overall in comparison to Inflammation(-)MetS(-)]. Moreover, we observed that individuals with UTRS are those associated with both inflammation and/or MetS. Our results demonstrated the potential combined effect of MetS and inflammation towards resistance to treatment. Given that overall-TRS/UTRS are unpredictable while both inflammation and MetS can be early detected and managed, our findings shed new light on the possibility to better prevent treatment resistance in SZ
Interactions of insulin aspart hexamer and excipients with plasticized polyvinyl chloride surfaces: A comprehensive investigation combining molecular simulations and experiments
No full textInternational audienceInsulin aspart is a major therapeutic biomacromolecule used worldwide for the treatment of diabetes mellitus. It is administered either subcutaneously or intravenously, using infusion lines made most often from plasticized polyvinyl chloride (PVC). Unfortunately, its very nature makes it at high risk of surface interactions with the materials it can come into contact with, leading notably to greatly decreased concentrations and patient underdosing. In order to prevent this phenomenon, for which no adequate solution yet exists, in-depth knowledge of the behaviour of insulin aspart at the water-solid interface is needed. The aim of this work was to shed new light on this highly problematic interaction and explain the adsorption phenomenon of insulin aspart and its phenolic excipients (phenol and metacresol) to plasticized PVC tubings from a thermodynamic point of view by combining experimental and molecular dynamics simulations. Our results proved that the hexameric form of insulin aspart possesses an important affinity for the PVC surface, to which it adsorbs nearly instantaneously to, whilst phenol and metacresol interacts with the PVC / plasticizer interface of the material. The molecular simulations of these surface interactions correlate well with the sorption processes that can be assumed to happen with the negatively charged PVC surfaces. Thermodynamic values obtained via the molecular simulation process were used to model succesfully the experimental data. This combination of theoretical approaches could help us in predicting the risk of interfacial interactions in biomacromolecular systems
Identifying key predictors of deep brain stimulation outcomes – A feature importance analysis
No full textInternational audienceIntroduction - Data-driven prediction of Deep Brain Stimulation (DBS) effects represents the foundation for algorithms automating DBS programming. Several models aiming at predicting symptom improvement in correspondence with specific stimulation parameters have been presented in literature. They exploit features ranging from patients’ clinical characteristics, to measures extracted from fMRI scans or probabilistic mapping. However, the relationships between predictive features and clinical improvement are often underexplored. Therefore, this study aims to conduct a feature importance analysis to identify the most influential predictors of DBS outcomes.Methods - 2112 intra-operative stimulation tests of 65 patients were used to simulate the Volumes of Tissue Activated (VTAs) and to compute probabilistic volumes of therapeutic (Probabilistic Sweet Spots, PSS) and side effects (SE). Clinical, morphological, stimulation and probabilistic mapping-related features were calculated and DBS effects were categorized in 3 classes (side effects, low and high improvement). Feature importance was assessed with: univariate feature selection with ANOVA F-value, permutation importance and SHAP values. Results - Despite being based on different principles, all three approaches consistently identified the same top three most influential predictors. These were: “VTA volume” (F=269.5), “PSS-VTA centroid distance” (F=123.3) and “VTA-SE volume overlap” (F=115.9). SHAP analysis revealed that high values of these features drive the prediction towards side effects class, whereas low values shift it towards high improvement class. Low improvement is associated with high VTA volumes and distances to PSS, coupled with low overlap with SE. Conclusion - The findings highlight the predictive value of features derived from probabilistic mapping results in determining DBS outcomes. Clinical and anatomical features demonstrated limited predictive power. The high importance of the “VTA volume” may be attributed to the characteristics of the collected data: tests at the minimum amplitude yielding a therapeutic effect and maximum amplitude before onset of adverse effects
« Crise du professionnel à l'épreuve de la crise identitaire du Mourir »
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Design, synthesis and in vitro evaluation of non-steroidal anti-inflammatory prodrugs for osteoarthritis
No full textInternational audienceOsteoarthritis (OA), a degenerative joint disease characterized by chronic pain and stiffness, is the most common cause of disability in older adults. To date, OA lacks curative treatment and medical care is limited to symptom relief particularly through the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). However, gastrointestinal and cardiovascular adverse effects and only limited benefits in long-term relief of pain are still associated. Moreover, efficiency is in part impeded by rapid clearance of the drugs and by the special physiological environment of the joint impeding deep penetration of drugs. Hence, to overcome those limitations and improve patient outcome, developing new therapeutic approaches based on anti-inflammatory prodrugs with prolonged drug residence time within the joints appears as a promising strategy in OA. We report herein the development of NSAID prodrugs, derived from diclofenac and naproxen, bearing a positively charged quaternary ammonium (QA) to target the negative-fixed charge density in cartilage by the mean of electrostatic interactions. Our charge-based targeted approach aims to extend the residence time of NSAID within the cartilaginous tissues, leading to a potential decrease of side effects and improved efficiency of locally released drugs. Syntheses of various amide and esters prodrugs of diclofenac and naproxen bearing a QA function were performed, including some hypoxia-activated prodrugs. Since most diclofenac derivatives suffered from high instability preventing any further development, we focused on the naproxen derivatives that were relatively stable in PBS buffer over a 24-hour period even if three different degradation patterns were observed in murine plasma. A preliminary screening of their in vitro anti-inflammatory efficacy highlighted a correlation between the PGE-2 inhibition and these cleavage patterns. These results support further in vitro and in vivo evaluations of four of these derivatives in OA models
Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis
No full textInternational audienceBackground & aims: Whether the dynamics of non-invasive tests (NITs) correlate with hepatocellular carcinoma (HCC) risk in patients with cirrhosis following sustained virological response (SVR) remains unknown. Thus, we aimed to describe NIT dynamics and assess their correlation with HCC risk.Methods: The dynamics of NITs (fibrosis-4 index [FIB-4], aspartate aminotransferase-to-platelet ratio index [APRI] and liver stiffness measurement) were described in patients with cirrhosis after SVR included in two prospective French multicenter cohorts (ANRS CO22 Hepather and CO12 CirVir) between 2006 and 2015. To assess their relationship with the risk of HCC, a joint modeling approach was employed using both standard and flexible models adjusted for age and sex. The impacts of NIT current value and slope during follow-up on HCC risk were assessed, considering competing risks of death.Results: A total of 3,067 patients with cirrhosis who achieved SVR were analyzed, among whom 228 (7.4%) developed HCC and 210 (6.9%) died during a 26-month follow-up. All NITs were increased at baseline in patients who ultimately developed HCC, whereas platelet counts were lower. All NITs improved in patients who did not develop HCC. More varied changes were observed during the follow-up of patients who ultimately developed HCC. Joint model analyses showed that current values of FIB-4, APRI and platelet count at any time impacted HCC risk. Only FIB-4 and APRI slopes influenced the same outcome. When considering NIT current value and slope simultaneously, only the current value of NITs impacted HCC risk while the slopes were not informative.Conclusions: The dynamics of NITs following SVR do not identify patients with cirrhosis who could be safely excluded from surveillance programs. NIT current value is more informative than slope, which will necessitate regularly re-assessment of HCC risk to design individualized surveillance strategies.Impact and implications: It has been postulated that monitoring non-invasive test (NIT) dynamics following HCV cure may provide information on the residual risk of hepatocellular carcinoma (HCC) in patients with cirrhosis and may allow for the discontinuation of surveillance in certain patient subsets. We analyzed data from over 3,000 patients and found that while all NITs improved in patients with cirrhosis who did not develop HCC, those who eventually developed liver cancer showed more varied changes in these tests. Specifically, the current values of tests like FIB-4 (fibrosis-4 index) and APRI (aspartate aminotransferase-to-platelet ratio index) were linked to an increased risk of HCC, while their slopes did not provide additional useful information, suggesting that dedicated prospective studies are warranted to define how repeated measurement of NITs could be combined with other variables into HCC risk stratification algorithms. Until then, HCC surveillance should be maintained in all patients with cirrhosis following HCV eradication, even in case of decreased NIT values
Management of thrombocytopenia and anticoagulant therapy in patients with hematological malignancy on chemotherapy: a binational prospective study (TAT study)
No full textInternational audienceAnticoagulant use in patients with hematological malignancies treated on intensive chemotherapy represents a management challenge because of concomitant thrombocytopenia. This prospective multi-center cohort included 100 patients with hematological malignancies on anticoagulation. The aims of the study were to assess the incidence of WHO grade ≥ 2 bleeding, describe physician management strategies during thrombocytopenia (platelet count < 50 × 109//L), and examine short-term outcomes and risk factors for bleeding and thrombosis. Median patients age was 60 years and median duration of severe thrombocytopenia was 16 days. The 30-day cumulative incidence of WHO grade ≥ 2 bleeding was 29.3% (95% CI 19.4-39.8), grade 4 bleeding was 7.2% (95% CI 2.8-14.2) and incidence of thrombus recurrence/progression was 6.2% (95% CI 2.2-13.3). No deaths occurred. The majority of patients received full-dose anticoagulation with a high platelet transfusion threshold. Half of the bleeding episodes grade ≥ 2 occurred with platelets counts between 20 and 50 × 109/L. Longer period of full-dose anticoagulation during thrombocytopenia was associated with increased bleeding risk (16 days [IQR: 6-29] for participants who presented ≥ grade 2 bleeding versus 7 days for those who did not [IQR: 2-14], p < 0.001). So was a HAS-BLED score ≥ 3 (HR = 9 [4.1-20], p < 0.001). Multiple myeloma diagnosis was associated with lower bleeding risk versus other hematological malignancies (HR = 0.2 [0.0-0.9], p = 0.05). Our study underscores the complex trade-off between preventing thrombotic events' progression or recurrence and avoidance of bleeding. We highlight specific clinical scenarios and consider different risk factors. Future randomized controlled trials are required for these complex situations to achieve a rationalization of their management