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Adult male patients with DKC1 mutations present early-onset pulmonary fibrosis and severe prognosis
No full textInternational audienceBackground Mutations in telomere-related genes (TRGs) are the main cause of monogenic familial pulmonary fibrosis. Dyskerin, encoded by the X-localised gene DKC1 , is involved in telomere maintenance. Methods This retrospective study aimed to further characterise the pulmonary phenotype of DKC1 -deficient patients with pulmonary fibrosis identified between 2010 and 2025 in our laboratory. Results We reported eight, as yet undescribed, to our knowledge, probands affected by pulmonary fibrosis associated with X-linked DKC1 deficiency. The median age at interstitial lung disease (ILD) diagnosis was 47 years. Four had idiopathic pulmonary fibrosis, two unclassifiable fibrosis, one idiopathic nonspecific interstitial pneumonia and one unknown. All patients displayed ectodermal abnormalities (premature hair greying, nail dystrophies, reticulated hyper- or hypopigmentation, tooth abnormalities and oral leukoplasia). Haematological abnormalities were found in four patients. Seven patients died during follow-up and one patient received a transplant. Median survival after ILD diagnosis was 22 months (range 3–81 months). Conclusions Compared with patients with pulmonary fibrosis associated with other TRG variants, those with pulmonary fibrosis associated with X-linked recessive DKC1 variants are younger and have a shorter survival time. Early identification and referral of these patients to an expert transplantation centre should be considered
Cyclic exclusive enteral nutrition versus partial enteral nutrition to maintain long-term drug-free remission in paediatric Crohn's disease (CD-HOPE): an open-label, endpoint-blinded, randomised controlled trial
No full textInternational audienceBackgroundFor children with Crohn's disease, there is a marked demand for long-term nutritional treatment strategies to avoid the side-effects related to drug treatment. We aimed to investigate whether paediatric patients with Crohn's disease responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of medication or surgery.MethodsIn this open-label, endpoint-blinded, randomised controlled trial (CD-HOPE) done in 21 hospitals of the GETAID pédiatrique network in France, eligible patients were aged 6 years to younger than 18 years with Crohn's disease (newly diagnosed or relapsing after drug treatment) who had reached clinical remission (weighted Paediatric Crohn's Disease Activity Index [wPCDAI] ≤12·5) after induction therapy with 6–12 weeks of exclusive enteral nutrition (EEN; 100% of calories). Stratified by age (≤10 years or >10 years) and relapse status, patients were randomly assigned (1:1) using block randomisation to receive either cyclic EEN (C-EEN; 100% of daily caloric requirements) for 2 weeks every 8 weeks for at least six cycles or daily partial enteral nutrition (PEN; 25% of daily caloric requirements) for 52 weeks. Oral MODULEN IBD was used for both. Except for the 2-week intervals of EEN in the C-EEN group, food access was not restricted. The primary endpoint was relapse rate at 12 months. A relapse was defined as: (1) a wPCDAI score greater than 12·5 at two successive visits, or (2) a wPCDAI greater than 12·5 once and the need for Crohn's disease-related surgery, medication, or study exit, or (3) a wPCDAI score continuously greater than 12·5 since the last study visit, or (4) incomplete wPCDAI and moderate or severe Physician Global Assessment at any timepoint. Primary and safety analyses were performed on an intention-to-treat basis. This trial was registered on ClinicalTrials.gov (NCT02201693) and is complete.FindingsBetween Dec 12, 2014, and Sept 4, 2018 (last patient visit Oct 2, 2019), 112 patients were screened and 100 patients (70 boys and 30 girls) were randomly assigned to C-EEN (n=49) or PEN (n=51). Median age of participants was 12 years (IQR 11–13) in the C-EEN group and 13 years (11–14) in the PEN group. At 12 months, 24 (49%) of 49 patients had relapsed on C-EEN compared with 39 (76%) of 51 patients on PEN (adjusted odds ratio 0·29 [95% CI 0·13–0·70], p=0·0051). 19 adverse events occurred in 17 patients: four serious adverse events in four patients on PEN, not related to treatment, and 15 non-serious adverse events in 13 patients (nine in seven patients on C-EEN and six in six patients on PEN). The serious adverse events were all related to Crohn's disease relapse requiring hospitalisation for rescue therapy. Six adverse events were possibly related to study treatment: one patient in the C-EEN group reported transient vomiting and diarrhoea at the start of the first EEN cycle, one patient in the C-EEN group developed anorexia and, in the PEN group, four patients reported either weight loss, nausea, Crohn's disease relapse, or skin infection. No malignancy or death was reported in this study.InterpretationC-EEN was superior to PEN in maintaining clinical remission over 1 year in paediatric patients with Crohn's disease responding to EEN induction therapy. These findings suggest a new way to use nutritional therapy for maintaining drug-free long-term remission in patients with Crohn's disease who are responding to EEN induction therapy.FundingAssistance Publique-Hôpitaux de Paris and Nestlé Health Science
Subdiffusive fractional limit of a jump-renewal equation
No full textIn this paper, we consider an age-structured jump model that arises as a description of continuous time random walks with infinite mean waiting time between jumps. We prove that under a suitable rescaling, this equation converges in the long time large scale limit to a time fractional subdiffusion equation
Systematic home visit planning prior to hospital discharge: a propensity-score matched comparative cohort study of over one million mother-infant dyads with one-year follow-up
No full textInternational audienceProblemMaternal mental health problems are leading causes of morbidity and mortality in high-income countries, yet follow-up after birth remains inconsistent.BackgroundSystematic postnatal home visits are recommended but many women do not receive them. clinical and economic impact of a structured scheduling of visits before discharge has not been fully evaluated.AimTo determine whether systematically arranged postpartum home visits were associated with reduced maternal rehospitalisations for mental health conditions. Secondary objectives included maternal and infant outcomes and healthcare costs within the first year.MethodsWe conducted a matched cohort study using national administrative data from 1297,646 low risk mother-infant dyads. In the intervention group, a midwife home visit was scheduled before discharge. Controls were matched on demographic and obstetric variables. The main outcome was maternal rehospitalisation for mental health conditions (ICD-10 codes F30–F45, F48, including depression or anxiety) within one year postpartum, excluding psychoses (F20–F29). Secondary outcomes included all-cause rehospitalisation for mothers and/or infants, use of emergency services, mortality, and overall healthcare costs.FindingsA scheduled home visit occurred in 95 % of cases in the intervention group, compared to 52 % in controls (p < 0.0001). The intervention was associated with fewer maternal mental health-related rehospitalisations (RR=0.82, p < 0.0001) and slightly reduced overall rehospitalisation rates for mothers and infants. Mortality was unchanged. Mean healthcare costs were marginally lower in the intervention group.DiscussionSystematic discharge planning may improve continuity of care and reduce psychiatric morbidity.ConclusionsPostpartum home visit scheduling supports better outcomes and may offer modest economic benefits
Utility of CA125 KELIM in predicting benefit from hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer: pooled analysis of KGOG3042 and KOV-HIPEC-01
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Differences between image-based and imageless robotics for total knee arthroplasty – an overview
No full textInternational audienceRobot-assisted total knee arthroplasty (TKA) has revolutionized implant positioning by enhancing surgical precision. However, significant differences exist between image-based and imageless robotic systems, influencing their accuracy, workflow, and potentially clinical outcomes. As such, this review aims to provide a structured comparison between image-based and imageless systems for TKA relevant to the surgeon. Image-based systems utilize preoperative imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) to construct three-dimensional (3D) anatomical models for surgical planning and intraoperative guidance. In contrast, imageless systems rely on intraoperative anatomical landmark registration, reducing costs and radiation exposure but yielding a potential higher inaccuracy to define the joint-specific coordinate system. This current concepts review examines key differences between these technologies, focusing on coordinate system accuracy, anatomical landmark identification, resection precision, and clinical implications. Image-based systems may demonstrate superior accuracy in defining coordinate systems, particularly for femoral and tibial rotational axes, yet involve higher costs and logistical complexity. Imageless systems offer real-time adaptability and avoid preoperative imaging but may be more susceptible to anatomical registration errors. Comparative clinical studies suggest similar coronal plane alignment error between the two approaches, though image-based systems may offer advantages in tibial slope precision. Radiation exposure is an important consideration, as it varies significantly based on imaging protocols and may warrant greater attention from surgeons, especially for patients who receive frequent CT follow-up. As well, while both system types allow for assessing patellofemoral tracking, in addition patient-specific 3D models allow to restore the native trochlea orientation. Although both systems improve implant positioning compared to conventional techniques, evidence on mid- and long-term improved clinical outcomes compared to the conventional technique is still lacking
Generating Efficiently Realistic Counterfactual Explanations
No full textInternational audienceThis article introduces VCNet -Variational CounterNet -a method for generating realistic counterfactuals, and its extension ImmutableVCNet. VCNet aims to generate counterfactuals that are representative of their predicted classes in the context of tabular data. Moreover, it aims to overcome the limitations related to the posthoc character and optimization procedure of the state-of-the-art approaches, by reducing the computing time of the counterfactual generation and reaching high levels of validity. However, state-of-the-art methods that succeed in overcoming the aforementioned limitations suffer from a lack of realism with regard to the counterfactuals generated. VCNet addresses this concern by adding realism constraints to the counterfactual generation process. Our approach is based on a conditional variational autoencoder (cVAE) to model the distributions for every class at once. Thus, generated counterfactuals not only belong to the data distribution but belong to the data distribution of a given class. The ImmutableVCNet extends VCNet to overcome the limitation of handling immutable features. We conducted several ablation studies to investigate the impact of the different choices within the VCNet architecture. Furthermore, we conducted empirical studies that demonstrate the significant benefits of our approach in generating realistic counterfactuals. We evaluate VCNet against ImmutableVCNet and also ImmutableVCNet against a variety of state-of-the-art counterfactual methods
Reimagining Urban River Bathing in Europe: A Multisectoral and Interdisciplinary Dive Into Lyon's Rivers (France)
No full textInternational audienceUrban river bathing is re‐emerging across Europe, driven by social demand and climate change impacts. The Urban Bathing Consortium, an interdisciplinary and intersectoral consortium initiated at the University of Lyon (France), is at the forefront of studying the challenges and opportunities of creating and managing healthy, safe, and accessible river bathing spaces. Through interdisciplinary collaboration among researchers and stakeholders, the consortium proposed an analytical framework, identifying seven critical dimensions for urban river bathing: the history and revival of city‐river relationships, legal and regulatory frameworks, bathing water quality, river drowning risks, river ecosystems, social perspectives, and urban planning. By examining these dimensions with state‐of‐the‐art approaches and drawing on Lyon's experiences, the study provides scientific insights and practical recommendations for future sustainable urban river bathing development. These include revitalizing historical city‐river connections, aligning local regulations with EU guidance, advancing holistic microbial water quality control, enhancing safety measures, incorporating ecological considerations, balancing competing river uses in urban planning, and addressing social needs for inclusive river governance
Radiobiology Contributions and Perspectives in Hadron Therapy, with a focus on carbon ions: Report from the workshop Hadron therapy for life, Caen, March 2025
No full textISTCTInternational audienceThe "Hadrontherapy for Life" symposium in Caen, France highlighted that a new era of radiobiology is fundamental for advancing particle therapy to the next level. A radiobiology capable of integrating molecular biology and omics technologies is needed to deeply analyze treatment responses and underlying mechanisms.Key challenges discussed at the symposium included tumor hypoxia, which remains only partially mitigated by high-LET radiation, and the specificity of carbon ions, or more broadly, high LET particles, considered as "new drugs" capable of providing systemic benefits beyond local tumor control, including their potential to promote immunogenicity. Moreover, emerging modalities, such as Ultra High Dose Rate irradiation, and spatial fractionated beam were also discussed, with consensus that all require dedicated and coordinated radiobiological investigations.Infrastructure presentations highlighted the international capabilities of leading centers in Europe and Asia, emphasizing the importance of integrating radiobiology into clinical programs, advancing multi-ion experimentation, and adopting innovative experimental models, such as organoids and/or 3D cell cultures. Participants also stressed the need for greater access to animal experimentation facilities, which are essential for accelerating progress in the field. Furthermore, the meeting underscored translational endpoints such as biomarker development, a hot topic in current radiotherapy. The C400 accelerator enables Caen to incorporate radiobiology from its very inception, establishing a European hub for collaborative research. Round-table discussions emphasized the importance of harmonized protocols, dedicated in vivo irradiation rooms, international training programs with exchange of students and researchers, and comprehensive patient biobanking.In summary, the symposium reinforced the essential role of radiobiology in advancing hadrontherapy (HT), providing strategic directions for translational research, infrastructure development, and international collaborations to accelerate personalized and effective particle therapy
Are There Differences in Ankle Mechanics After Total Ankle Arthroplasty in Patients Suffering From Post-fracture vs Post-sprain End-Stage Ankle Osteoarthritis?
No full textInternational audienceBackground: To our knowledge, no study is available comparing the change in ankle mechanics during gait after total ankle arthroplasty (TAA) based on the origin of the osteoarthritis. As the nature of trauma is different in patients sustaining post-fracture ankle osteoarthritis (PFOA) from those sustaining post-sprain ankle osteoarthritis (PSOA), it could be expected that the outcomes of TAA, in terms of ankle mechanics during gait, would be different in the 2 groups. A prospective matched comparative study was therefore performed to investigate whether patients sustaining PFOA had different outcomes in terms of changes to ankle mechanics during gait (before surgery vs 1 year after surgery), compared with patients sustaining PSOA. Methods: Fifteen patients with PFOA and 15 patients with PSOA scheduled for primary TAA for pain relief were recruited and peer-matched based on their demographic and spatiotemporal data. All patients underwent a 3D gait analysis before and after surgery, during which a kinematic and kinetic multi-segment foot model was used to quantify inter-segmental joint kinematics and kinetics. Results: The PFOA group exhibited significantly lesser pre- vs postoperative increases in ankle (Shank-Calcaneus) joint peak power, and ankle (Shank-Calcaneus) joint work after TAA compared with the PSOA group. Furthermore, the results demonstrated a trend toward greater increases in peak ankle (Shank-Calcaneus) joint plantarflexion moment and in negative ankle (Shank-Calcaneus) joint work for the PSOA group compared with the PFOA group. Conclusion: This study suggests that patients sustaining PFOA have smaller pre- to postoperative gains in ankle (Shank-Calcaneus) joint power and ankle (Shank-Calcaneus) joint work during gait after TAA compared with patients sustaining PSOA, with modest between-group effects. Although evidence in TAA is lacking, insights from knee replacement suggest prehabilitation and nutritional support may mitigate deficits, representing a potentially essential strategy for PFOA patients requiring further validation