Portail HAL de l'Université Picardie Jules Verne
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What is your diagnosis? A spontaneous echo contrast in Waldenström macroglobulinemia
No full textInternational audienc
PHENO-RAG: An artificial intelligence tool for guideline-informed management decisions in hepatocellular carcinoma
No full textInternational audienceBackground & aims: Management of hepatocellular carcinoma (HCC) poses unique challenges due to its development in the context of chronic liver disease and the availability of multiple treatment options. Although multidisciplinary team (MDT) management improves outcomes, universal MDT discussion is resource-intensive, underscoring the need for effective patient-stratification tools. We developed a novel large language model (LLM) framework, PHENO-RAG, that integrates contemporary HCC management guidelines with patient-specific clinical data.Methods: We retrospectively analysed 489 clinical reports from 424 patients treated at a tertiary referral centre between September 2020 and November 2024. Eight locally hosted LLMs were tested: Llama-3-8B/70B, GPT-oss-20B/120B, Qwen-3-8B/80B, and Falcon-7B/40B. Two ablation studies assessed clinical concept extraction (using REGEX, pure LLMs, and hybrid REGEX+LLM pipelines) and decision generation across six configurations (zero-shot/few-shot with unstructured vs. structured notes, with and without retrieval-augmented generation [RAG] using clinical guidelines). The primary outcome was exact-match accuracy against real-world clinical decisions for treatment allocation, clinical complexity, and recommendation for MDT discussion.Results: GPT-oss-120B+REGEX achieved the best overall agreement (median F1 for categorical concepts 0.92 [95% CI 0.85-0.95]; median intraclass correlation coefficient for numerical parameters 0.93 [95% CI 0.85-0.94]). For decision support, accuracy increased with structured inputs, few-shot exemplars, and RAG across all models. Under the strongest configuration (few-shot+RAG on structured notes), GPT-oss-120B reached 86.5% exact match for treatment allocation, 88.6% for clinical complexity, and 66.9% for MDT recommendation; Llama-3-70B achieved 80.8%, 83.4%, and 63.0%, respectively. Performance in the baseline zero-shot, unstructured-note configuration was substantially lower.Conclusions: PHENO-RAG delivers accurate, guideline-concordant support for HCC treatment allocation and complexity grading from real-world notes, with performance driven less by model family alone than by hybrid extraction, input structuring, in-context examples, and evidence retrieval. MDT referral remains the hardest task - appropriate for prioritization rather than automation. Prospective, multi-site and multimodal validation is warranted.Impact and implications: Clinical decisions in the management of hepatocellular carcinoma are complex and multiparametric, requiring resource-intensive multidisciplinary care and creating challenges for optimal treatment allocation across different healthcare settings. We developed PHENO-RAG, a large language model-based framework that combines patient phenotyping through automated clinical information extraction from real-world clinical notes with treatment decision support, based on international guidelines. Our framework demonstrated concordance of 86.5% with real-world clinical decisions for treatment allocation and 88.6% for clinical complexity assessment, suggesting potential to enhance decision consistency and quality of care. In clinical practice, this AI-assisted framework could help standardize hepatocellular carcinoma management workflows, support training of hepatology and oncology fellows, assist in quality assurance programs, and facilitate more systematic identification of complex cases requiring multidisciplinary consultation, particularly in resource-constrained settings
Guest editorial – Stabilization safety, and security of distributed systems
No full textPart of special issue on Stabilization, Safety, and Security of Distributed Systems from 24th International Symposium on Stabilization, Safety, and Security of Distributed Systems (SSS 2022), November 2022, Clermont-Ferrand, Franc
Cognitive impairment predicts adverse outcomes in chronic kidney disease
No full textInternational audienceBackgroundCognitive impairment (CI) affects self-management in chronic diseases, leading to poor decision-making, delayed care, and increased mortality. The specific impact of CI on adverse outcomes in CKD remains poorly explored.MethodsThe french CKD-REIN cohort included 3033 patients with CKD stage 2–5 and 5 years of follow-up. CI was assessed using the Mini-Mental State Examination (MMSE), and eGFR was estimated with the CKD-EPI creatinine equation. Cox models evaluated the risks of all-cause mortality, kidney replacement therapy (KRT) initiation, and major adverse cardiovascular (CV) events (MACEs).Results3004 patients were included in the analysis (mean age: 67 years, mean eGFR 34 mL/min/1.73 m2), and 64%, 23% and 13% respectively had MMSE scores of >26, between 24-26, and 26: HR [95% confidence interval] was 1.42 [1.12, 1.81], 1.57 [1.19, 2.07], and 1.32 [1.02, 1.70] for KRT initiation, all-cause mortality and MACE respectively. CI was associated with all-cause mortality in the MMSE 24-26 group also (HR: 1.45 [1.15, 1.83]).ConclusionIn CKD, a baseline MMSE score 26. These results highlight CI’s prognostic value, and suggest that earlier detection could better personalize management, particularly for kidney and CV complications
The use of applied improvisation at university: a mini-review
No full textInternational audienceAim This mini review aimed to synthesize current evidence on applied improvisation programs in higher education across disciplines, identifying their impact, implementation, evaluation methods, and future research directions. Methods Following PRISMA-ScR guidelines, a systematic search was conducted across six databases, covering publications from 1999 to 2024. Inclusion criteria encompassed empirical studies involving university populations engaging in theatrical or applied improvisation interventions. After screening, 54 relevant studies were included. Data extracted included study characteristics, participant demographics, intervention methods, evaluation methodologies, and outcomes. Results Most studies originated from the United States (70.4%), targeting students (85.2%), particularly in healthcare education (61.1%). Interventions varied from single workshops to multi-session courses, aiming to improve skills such as communication (62.9%), empathy (25.9%), collaboration (25.9%), confidence (22.2%), and stress management (14.8%). Evaluations often relied on satisfaction surveys or in-house questionnaires, with only 27.8% using standardized tools. Methodological variability and reliance on self-reported measures limited comparability and generalizability of the results. Conclusion Applied improvisation demonstrates potential as an innovative educational tool in higher education, enhancing key skills across various disciplines. However, significant methodological limitations—including heterogeneous interventions and assessments—hinder generalization of findings. To advance the field, future research should develop standardized assessment tools, establish consistent intervention protocols, and conduct randomized controlled longitudinal studies to assess the effectiveness and the durability of outcomes. Strengthening interdisciplinary collaborations and employing rigorous research methodologies are essential to optimize the use of applied improvisation in higher education
Cardioprotective effect of intracoronary zinc administration in isolated rat hearts during ischemia-reperfusion following intermittent hypoxia exposure in vivo
No full textInternational audienceIntroduction Zinc is an essential trace element with antioxidant and signaling functions critical to cardiac physiology. This study investigated the role of zinc in myocardial ischemia-reperfusion (IR)-induced cardiac damage using a rat model, and whether zinc deficiency induced by intermittent hypoxia (IH) exacerbates cardiac injury. Methods Regional IR was performed in isolated rat hearts, and zinc concentrations were measured in coronary effluents. Plasma zinc status was assessed following 14- or 35-day IH exposure (1-min cycles alternating 21% and 5% FiO₂, 8 h/day). The cardioprotective effects of intracoronary zinc administration with the ionophore pyrithione were evaluated based on arrhythmias, infarct size, and contractile recovery. Results Myocardial IR induced significant zinc release upon reperfusion (615.7 ± 78.2 nM vs. 374.5 ± 40.3 nM pre-reperfusion, p < 0.01). Zinc administration during reperfusion reduced arrhythmia duration (358.0 ± 61.7 sec vs. 559.9 ± 31.6 sec, p < 0.01) and improved myocardial recovery. IH exposure led to reduced plasma zinc levels (10.3 ± 0.5 µM vs. 13.0 ± 1.2 µM, p = 0.057) and significantly increased infarct size following IR (43.9 ± 4.2% vs. 29.2 ± 4.3%, p < 0.05). Zinc-pyrithione treatment during reperfusion abolished the deleterious effects of IH on infarct size. Discussion IH-induced zinc deficiency exacerbates cardiac vulnerability to IR injury, while zinc restoration through targeted administration mitigates this damage. Zinc’s protective effects may involve antioxidant action, calcium homeostasis, and signaling modulation. Conclusion Zinc plays a critical role in limiting IR-induced cardiac damage. Zinc supplementation during reperfusion may offer therapeutic benefit, particularly in conditions associated with chronic IH, such as obstructive sleep apnea
Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study
No full textInternational audience6502 Background: BPDCN is a rare, clinically aggressive hematological malignancy primarily involving the skin, bone marrow, and lymph nodes. CD123 (IL-3Rα) is highly overexpressed on the surface of all BPDCN blasts making it an ideal target for novel immunochemotherapy. PVEK is a first-in-class antibody-drug conjugate comprising a high-affinity CD123 antibody, cleavable linker, and an indolinobenzodiazepine pseudodimer payload. Here, we present the primary analysis of efficacy and safety from CADENZA. Methods: In the open-label, multicenter, phase 1/2 CADENZA study, adults with BPDCN received PVEK monotherapy intravenously on day 1 of a 21-day cycle, as a <30-min outpatient infusion. Primary endpoint was the rate of composite complete response, defined as complete response (CR) + clinical CR (CR with minimal skin abnormality [CRc]) in frontline (1L) pts. Key secondary endpoints were duration of CR + CRc, median overall survival (OS), overall response rate (ORR), % of pts who were bridged to stem cell transplantation (SCT) after PVEK, and safety and tolerability. Results: At primary analysis (data cutoff: October 2, 2024), CADENZA enrolled 84 pts with CD123-positive BPDCN who received PVEK at the recommended phase 2 dose (RP2D) of 0.045 mg/kg every 21 days, including 33 pts with 1L BPDCN (median age, 73.0 [range, 48-84]; ≥65 years, 91%; male, 82%) and 51 pts with relapsed/refractory (R/R) BPDCN (median age, 69.0 [range, 19-85]; ≥65 years, 59%; male, 82%). Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp. Median follow-up was 21.5 mo for 1L pts and 24.1 mo for the R/R group. Among 1L pts, CR + CRc was 70% (95% CI, 51.3-84.4) and median duration of CR + CRc was 9.8 months (mo) (95% CI, 4.6-Not Reached [NR]); ORR was 85%. Median OS was 16.6 mo (95% CI, 11.4-NR). Among 13 (39%) 1L pts bridged to SCT, CR + CRc was 92% (95% CI, 64.0-99.8) and median OS was NR. In the R/R group, CR + CRc was 14% and median duration of CR + CRc was 9.2 mo (95% CI, 2.4-NR); ORR was 35%. Median OS was 5.8 mo (95% CI, 3.9-8.4) and 12% of pts bridged to SCT. Median (IQR) PVEK treatment exposure was 5 (4-9) cycles for the 1L group and 3 (2-5) cycles for the R/R group. Safety was assessed in all 84 pts. The most common treatment-emergent adverse event (TEAE) was peripheral edema (any grade, 54%; grade ≥3, 12%). TEAEs led to discontinuation in 9% and 7% of pts with 1L and R/R BPDCN, respectively. No capillary leak syndrome (CLS) events or treatment-related deaths were reported, and 2 (2%) pts experienced veno-occlusive disease of grades 2 and 3 after cycles 4 and 8, respectively, which resolved. Conclusions: PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses. PVEK was tolerable at the RP2D. The safety profile was manageable, with no CLS events. These results support PVEK as a potential new treatment option for adult pts with BPDCN. Clinical trial information: NCT03386513
Flexible TEMPO-cellulose/silver selenide nanocomposites with advanced optical, electrical, and antimicrobial performance
No full textInternational audienceTransforming dielectric polymers into conductive or semiconductive materials opens new avenues for advanced and unprecedented applications. Herein, flexible films were fabricated from TEMPO-oxidized cellulose nanofibers/silver selenide (T-CNF/Ag2Se) nanocomposites. Ag2Se particles were in situ prepared in the presence of TEMPO-oxidized cellulose nanofibers to limit the Ag2Se formation within the nanopores of the TEMPO-oxidized cellulose nanofibers. XRD and FTIR patterns verified the effective embedding of Ag2Se nanoparticles within the T-CNF matrix, where Ag2Se crystallized exclusively in the orthorhombic β-Ag2Se phase. For optoelectronic applications, the optical features were investigated, and Ag2Se has a great impact on transmittance, reflectance, optical band gap, and Urbach energy of CNF. The transmittance was reduced from 10% to 2% in the visible region, while the optical band gap dropped from 4.46 eV for CNF to 2.65 eV for CNF/Ag2Se I. Compared with pure CNF, the CNF/Ag2Se I nanocomposites showed broader M″ peaks that shifted towards higher frequencies, indicating enhanced charge-carrier dynamics due to the additional conductive pathways introduced by the Ag2Se nanoparticles. At 313 K, conductivity followed the order of CNF < CNF/Ag2Se III < CNF/Ag2Se < CNF/Ag2Se II < CNF/Ag2Se I, with the conductivity increased by three orders of magnitude for CNF/Ag2Se I compared with that for the pure CNF. The antimicrobial performance of CNF/Ag2Se at different concentrations was evaluated, and it exhibited high toxicity against E. coli, S. typhimurium, and C. albicans, while S. mutans exhibited more resistance against the nanocomposite materials
Uncovering the dynamics of mucosa-associated microbiota in post-operative recurrence of Crohn’s disease
No full textInternational audienceBackgroundAbout 50 to 75% of Crohn’s Disease patients (CD) need bowel resection. Postoperative recurrence of Crohn’s disease is frequent. Here, we investigate the evolution of the mucosa-associated microbiota along the Rutgeerts score measuring endoscopic recurrence after surgery.MethodsWe used 16S rRNA and ITS2 sequencing to profile the mucosa-associated microbiota of biopsies from CD patients at the time of surgery (M0, n=139) and later, at the time of endoscopic assessment of recurrence (M6, n=125).ResultsWhile the effect of surgery and recurrence were moderate on the overall microbiota composition, we identified specific microbial signatures displaying differential relative abundance when accounting for clinical covariates. The relative abundance of certain species, notably a decrease of Faecalibacterium prausnitzii, or increase of Akkermansia muciniphila, was differentially associated with a whole range of Rutgeerts score or with more specific scores characterizing the inflammation of the anastomosis or the ileum. In addition, machine learning performances were impacted by the consideration of the Rutgeerts score as a multilevel prediction instead of a binary classification, further confirming the need to consider its full range. Finally, we investigated the community dynamics, which highlighted a denser network organisation after surgery and in the absence of recurrence, along with changes in keystone species.ConclusionAltogether, these results provide further understanding of the effects of ileal resection patients with CD and show that disease recurrence is a dynamic process characterized by several waves of changes in the microbiota composition