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The Effects of Burst Steroid Therapy on Short-term Decongestion in Acute Heart Failure Patients With Pro-inflammatory Activation: A Post Hoc Analysis of the CORTAHF Randomized, Open-label, Pilot Trial
No full textInternational audienceBackground: The effect of steroids on congestion in patients with acute heart failure (AHF) is not known.Methods and results: Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds for the prednisone group compared to usual care at day 31 was 1.77 (95% CI 1.17-2.84; P = 0.0066) in all patients and 2.41 (95% CI 1.37-5.05; P = 0.0016) in patients with IL-6 > 13 pg/mL at baseline. In patients with congestion scores ≥ 7 at baseline, the effects of prednisone therapy on the EQ-5D visual analog scale score were 4.30 (95% CI 0.77-7.83) points at day 7 and 5.40 (0.51-10.29) points at day 31, accompanied by lower heart rate and respiratory rate and higher oxygen saturation compared to usual care.Conclusions: In patients with AHF and inflammatory activation, 7-day steroid therapy was associated with reduction in signs of congestion up to day 31. These results need confirmation in larger studies examining potential effects of steroids on congestion, diuresis, fluid redistribution and vascular permeability as well as clinical effects in AHF
Nonparametric optimal density estimation for censored circular data
No full textWe consider the problem of estimating the probability density function of a circular random variable observed under censoring. To this end, we introduce a projection estimator constructed via a regression approach on linear sieves. We first establish a lower bound for the mean integrated squared error in the case of Sobolev densities, thereby identifying the minimax rate of convergence for this estimation problem. We then derive a matching upper bound for the same risk, showing that the proposed estimator attains the minimax rate when the underlying density belongs to a Sobolev class. Finally, we develop a data-driven version of the procedure that preserves this optimal rate, thus yielding an adaptive estimator. The practical performance of the method is demonstrated through simulation studies
Enhancing the Description-Detection Framework with Semantic Clustering Using Biostransformers
No full textInternational audienceEvent-Based Surveillance Systems (EBS) are crucial for detecting emerging public health threats. However, these systems face significant challenges, including overreliance on manual expert intervention, limited handling of heterogeneous textual data, etc. The Description-Detection Framework (DDF) addresses some of these limitations by leveraging PropaPhen (Core Propagation Phenomenon Ontology), UMLS, and OpenStreetMaps to detect suspicious health-related cases using spatiotemporal and textual data. However, DDF is restricted to detection and lacks the ability to classify the detected observations into meaningful categories.To adress this limitation, we propose to enhance DDF by incorporating a clustering-based classification process. This enhancement employs BioSTransformers, a pretrained biomedical language model built on Sentence Transformers trained on PubMed data, to compute semantic similarity between observations. By capturing domain-specific semantic relationships, BioSTransformers enables clustering that integrates biological semantics with spatiotemporal context, outperforming traditional methods from the literature in observation classification. Our proposed approach reduces the dependency on manual expert effort, improves the system's ability to process heterogeneous data, and enhances the accuracy and contextual relevance of case classification. The results demonstrate the potential of this method to advance EBS systems, providing a scalable and automated solution to public health surveillance challenges.</div
Les évacuations sanitaires de Mayotte vers La Réunion : un dispositif et des inégalités socio-territoriales
No full textInternational audienceL’éloignement des territoires d’outre-mer et l’inégale répartition des moyens et personnels médicaux entre l’Hexagone et les différentes régions ultramarines produisent des inégalités territoriales d’accès aux soins. Pour assurer la continuité territoriale des soins, des dispositifs institutionnels d’évacuation sanitaire ont été mis en place. Le dispositif EVASAN organise ainsi le transfert de patient.e.s de Mayotte vers l’Hexagone et surtout vers l’Ile de La Réunion, plus proche et bien mieux dotée que Mayotte en termes d’infrastructures sanitaires. En effet, la pénurie de structures, d’équipements techniques et de personnels médicaux et l’absence de nombreuses spécialités médicales à Mayotte ne permettent pas d’y garantir un accès réel et égal aux soins. La recherche AccMinEv porte sur l’analyse du dispositif EVASAN en se centrant sur les trajectoires et expériences d’accompagnement des mineur.e.s évacué.e.s pour soins et de leur famille. Des enquêtes qualitatives par entretiens (140) et observations à Mayotte et à La Réunion ont été menées dans différents espaces (structures de soins et d’hébergement, familles d’accueil, associations, domiciles…) et auprès de différentes catégories (professionnels de santé, familles, anciens mineurs évasanés, travailleurs sociaux, bénévoles). En revenant sur les trajectoires de soins et d’accompagnement des mineur.e.s évacué.e.s, cette communication propose d’interroger les impensés du dispositif EVASAN en ce qui concerne les inégalités sociales de santé que le dispositif contribue lui-même à produire, et en les expliquant à l’aune du contexte territorial particulier de l’île (isolement géographique, pauvreté, réglementations dérogatoires en matière de politiques migratoire et sociale)
Janus kinase and calcineurin‐inhibitor combination in anti‐MDA5 dermatomyositis: No significant survival benefit but reassuring safety profile
No full textInternational audienceObjectives Anti‐MDA5 dermatomyositis (anti‐MDA5 DM) is the most severe subtype of dermatomyositis, due to its pulmonary involvement. Current treatment involves corticosteroids and immunosuppressants, but variability in responses exists. This study aims to evaluate the efficacy and safety of Janus kinase (JAK)– and calcineurin–inhibitor combination (JAK–CNI) in anti‐MDA5 DM patients. Methods A nested case–control study was conducted within a retrospective cohort of 234 anti‐MDA5 DM patients. Patients receiving JAK–CNI were matched 1:2 with comparators. All‐cause mortality or transplant within a year was compared using Cox proportional hazards models. Infectious and noninfectious side effects were also assessed. Results Twenty‐seven patients receiving JAK–CNI were compared to 52 matched controls. Almost all these patients had pulmonary involvement. Thirty‐nine (49%) died or were transplanted during follow‐up. No significant improvement in survival or transplant‐free survival was observed with JAK–CNI compared with comparators (hazard ratios 1.02, 95% confidence intervals [0.48–2.16]). Results were consistent regardless of intensive care unit (ICU) admission status and when analyses were restricted to patients with rapidly progressive interstitial lung disease. A trend toward a beneficial effect of the JAK–CNI combination was observed in non‐ICU patients. Infectious complications were frequent ( n = 49, 62%), with no excess risk in patients receiving JAK–CNI. Conclusion JAK–CNI showed a similar outcome to other immunosuppressive combinations. However, as the study included the most severe cases, the potential benefit of early JAK–CNI introduction in less severe forms cannot be dismissed, as suggested by the nonsignificant trend in non‐ICU patients. Future studies are needed to clarify the optimal timing and patient selection for JAK–CNI therapy in anti‐MDA5 DM
Intense optimization of oral therapy rapidly restores respiratory function in worsening heart failure patients
No full textInternational audienceAbstract Aims Breathlessness is the primary symptom of decompensated heart failure (HF), but the prevalence and evolution of persistent respiratory distress post‐hospitalization remain unclear. Methods and results The Longitudinal Observational Study for mIddle Term Follow‐up Patients Admitted for Acute Dyspnea in TunIsia (SIDI) study is a prospective and multicentre study on HF patients with preserved ejection fraction admitted for acute dyspnoea. Patients were followed for 6 months. The primary endpoint was to assess the incidence of persistent respiratory distress and factors linked to respiratory recovery at Day 90. The secondary endpoint was rehospitalization and/or death at Day 90 and 180. Among 231 patients, 140 had SpO 2 and respiratory rate data at Day 90. Persistent respiratory distress was observed in 97 (69%). Multivariable analysis found no association between respiratory recovery and sex, diabetes, hypertension, kidney disease or NT‐proBNP levels. However, intensive follow‐up ( n = 54) with oral neuroendocrine inhibition significantly improved respiratory parameters at Day 90 (adjusted HR: 5.70 [95% CI 2.13–18.28], P = 0.0001) compared with standard follow‐up ( n = 86) and reduced rehospitalization and/or death at Day 90 and 180. Conclusions Persistent respiratory distress is frequent in the months following HF hospitalization. Optimized guideline‐directed therapy and close follow‐up improve respiratory recovery. SpO 2 and respiratory rate monitoring should be integrated into HF management
A polysaccharide-based hydrogel platform for tumor spheroid production and anticancer drug screening
No full textInternational audienceExtracellular matrix mimics are still needed to grow cancer cells in 3D environments and study their evolution in vitro while precisely controlling relevant features. Most models currently use collagen, which is biomimetic but degrades quickly, or artificial polymers, which can be chemically modified but remain stiff. Herein we introduced a soft, non-adhesive, and resistant hydrogel platform for tumor spheroid production using a polysaccharide-based formulation. To ensure micro-structuring of the hydrogel and enable spheroid formation, 3D printed molds consisting of a network of 200-µmdiameter micropillars were used to generate microstructured hydrogel constructs that fit into a multiwell plate. This platform was validated for drug testing using three cancer cell lines (A673, MCF7 and U87) and 2 anticancer drugs (doxorubicin and paclitaxel). Drug response was assessed through brightfield microscopy monitoring and viability measurements after 48 h of treatment. This study validates the use of pullulan-dextran hydrogels for spheroid formation, combined with in situ drug screening.</div
Should Exogenous Ketone Body Supplementation Be Considered in Patients Hospitalized for Acute Heart Failure? Rationale and Design of the KETO-AHF Trial
No full textInternational audienceBackground: Acute heart failure (AHF) is associated with high mortality rates, and contemporary medical treatments provide limited benefits in survival. Emerging evidence suggests that exogenous ketone bodies may have beneficial cardiovascular effects in patients with heart failure. The KETO-AHF (KETOne Supplements in Patients Hospitalized for Acute Heart Failure) trial is designed to assess the clinical benefits of initiating ketone supplementation with 1,3-butanediol compared with placebo in patients hospitalized for AHF with reduced ejection fraction.Methods: KETO-AHF is a multicenter, randomized, double-blind, placebo-controlled trial investigating the effects of 1,3-butanediol (33 g 3 times daily) in patients hospitalized for AHF. Patients with symptoms and signs of AHF requiring intravenous loop diuretics and/or vasoactive treatment, elevated natriuretic peptides, and a left ventricular ejection fraction ≤ 35%, whether de novo or known heart failure, will be enrolled within 5 days of hospital admission. Participants will be randomized 1:1 to receive either 1,3-butanediol or placebo for a 30-day treatment period. The study aims to enroll 125 patients in each group. The primary endpoint is a hierarchical composite of all-cause mortality, heart failure rehospitalization, 6-minute walk test improvement, and reduction in NT-proBNP levels at 30 days.Conclusion: The KETO-AHF trial will provide insights into the effects of supplementation with the ketone body 1,3-butanediol in patients hospitalized for AHF
Pressure dependence of sound velocity, shear modulus, and yield strength of the amorphous 4:1 methanol-ethanol mixture to 78 GPa
No full textInternational audienceHigh-pressure elastic and plastic behavior of the amorphous solid, formed after solidificationof the mixture of methanol and ethanol in the volume ratio 4:1 (4:1-ME), was investigated usingthe technique of time-domain Brillouin scattering (TDBS). Isotropic nature of this solid, whosebulk modulus exceeds that of diamond at pressures above 60-70 GPa (provided the earlier measured dependence of its density on pressure, ρ(P), holds at P>60 GPa), was confirmedthanks to the high 3D-resolution of the TDBS technique. This permitted establishing of therelationship between elastic and plastic properties at high pressures because elastic response ofthe amorphous solid was not affected by anisotropy and texture, as is the case for crystallinesolids. Using the TDBS technique, we measured pressure dependence of the Brillouin oscillation frequencies, fB(P), of 4:1-ME and, consequently, of its longitudinal sound velocity,VL(P), and shear modulus, G(P), to P=78 GPa. To access pressure dependence of its yieldstrength, σy(P), we used the here-established secondary pressure scale, based on ourexperimental fB(P), and measured the maximal pressure gradients in the compressed sampleswhich are proportional to σy. We have found that the rapid increase of bulk modulus of 4:1-MEwith pressure, deduced from the ρ(P), earlier-measured to 60 GPa and here-extrapolated to 78GPa, is not accompanied by a similarly strong increase of its shear modulus and yield strength.The two parameters remain significantly below those of diamond at atmospheric and highpressures. Comparison of the here-measured σy(P) with the dependences B(P) and G(P)indicated that σy can be similarly-well approximated by linear functions where B or G serves asthe variable