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Left Ventricular Outflow Tract Obstruction in Critically Ill Patients: from Pathophysiology and diagnosis to the management with the “LVOTO” Bundle
No full textInternational audienceLeft Ventricular Outflow Tract Obstruction (LVOTO) is a dynamic and often underrecognized cause of hemodynamic instability in critically ill patients. While more common in those with anatomical features like septal hypertrophy or hypertrophic cardiomyopathy, it can also occur in hyperdynamic states such as septic shock, stress-induced cardiomyopathy, acute hemorrhage/hypovolemia, or after excessive inotrope administration—even in patients without any anatomical predisposition. Its clinical presentation is often subtle and can mimic other causes of shock, making early recognition essential. A high index of suspicion and a systematic echocardiographic approach are crucial for early diagnosis, identifying features such as hypercontractility, systolic anterior motion of the mitral valve, LVOT narrowing, and flow acceleration on Color Doppler Imaging. Doppler imaging—particularly color flow mapping and continuous-wave (CW)—is vital for confirming and localizing the obstruction. A “dagger-shaped”, late-peaking waveform of CW Doppler is pathognomonic. In cases with limited acoustic windows, transesophageal echocardiography represents an alternative.Management focuses on reversing underlying triggers and optimizing myocardial loading conditions. Discontinuation of pro-obstructive agents (e.g., inotropes), fluid resuscitation to enhance preload, and afterload augmentation using pure alpha-agonists (e.g., phenylephrine) can be very effective in further decreasing the LVOT pressure gradient. Selective use of short-acting beta-blockers might be considered to reduce contractility and heart rate. Lowering positive end-expiratory pressure (PEEP) may also benefit preload-dependent patients.We propose the “LVOTO bundle” to facilitate the treatment by summarizing key therapeutic steps. Timely and bundled-targeted interventions are vital to reverse this potentially life-threatening condition and improve outcomes in critically ill patients
Key parameters governing lithium-ion mobility in an ionic liquid tethered on metal oxide nanoparticles as solvent-free hybrid electrolytes
No full textInternational audienceHere, we have synthesized and characterized a series of new hybrid materials based on ionic liquids grafted on metal oxides to assess the design of solvent-free solid-state electrolytes. The aim of this study is to determine the key parameters affecting the ionic conduction properties of the materials. Several aspects were modulated, such as the chemical composition of the metal oxide (SiO2, ZrO2 or Al2O3), anchoring bond (silane chemistry or coordinative bond) and length and nature of the spacer (propyl, undecyl, or polyethylene glycol). The ionic conductivity of the hybrid composite mixed with the lithium salt reaches 4 x 10-5 S cm-1 without the addition of any solvents or plasticizers. This study reveals that although lithium mobility is affected by the molecular structure of the ionic liquid and grafting function, it is more driven by the organization of the ILs on the surface of the nanomaterial
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Global vs. regional effects of PEEP on recruitment and strain: Insights from Preclinical and Clinical Studies.
No full textInternational audienceIn Acute Respiratory Distress Syndrome (ARDS), regional aeration is often gravity-dependent, with Positive End-Expiratory Pressure (PEEP) recruiting the lung dorsally. While recruitability can be assessed globally, our aim was to determine the impact of PEEP on regional recruitability and regional strain. To achieve a large representation of recruitability, we studied two preclinical porcine models of acute lung injury ([ALI] 19 symmetrical and 10 asymmetrical ALI), 20 patients with ARDS of mixed etiology (mixed ARDS) and 15 with COVID-19 ARDS. All study subjects underwent a single-breath derecruitment maneuver from high to low PEEP to quantify recruitability using the recruitment-to-inflation ratio (R/I). The regional effects of PEEP on strain were assessed using Electrical Impedance Tomography (EIT). Symmetrical ALI animals had the highest R/I (1.39[1.04-1.66]), followed by mixed ARDS (1.06[0.70-1.23]), COVID-19 ARDS (0.66[0.51-0.98]), and asymmetrical ALI (0.45[0.22-0.85]). Dorsal regions had the highest recruitability (p=0.001), and differences between dorsal and ventral regions were higher in recruitable subjects. Increasing PEEP decreased ventral dynamic strain (p<0.01), with varying effects on dorsal dynamic strain. A paradoxical increase in dorsal dynamic strain associated with ventral hyperinflation could be observed across all groups, but more frequently in the less recruitable subjects. It was predicted by the EIT ventral-to-dorsal shift in ventilation normalized to the change in dorsal lung volume (p<0.001). In animals and patients with varying recruitability, a higher global R/I is associated with a higher effect on the dorsal versus ventral R/I. PEEP can paradoxically increase dorsal strain due to ventral overdistention, and this is detectable by EIT
OP03 Early kinetics of transmural healing in patients with Crohn’s Disease treated with risankizumab: Results of the multicenter prospective SKYNETICS study
No full textPrésentation oraleInternational audienceBackground We aimed to evaluate, in real-life practice, the kinetics of clinical, biochemical, and transmural efficacy of risankizumab in patients with Crohn’s disease (CD). Methods In this academic multicenter prospective study, adult patients (≥18 years) with CD who initiated risankizumab in routine practice for symptomatic CD according to PRO-2 with objective evidence of inflammation on ultrasound were included. Patients started risankizumab at a dose of 600 mg IV at weeks 0, 4, and 8, followed by 360 mg every 8 weeks (from W12) via an on-body injector. Ultrasound examinations were performed at W0, W4, and W12 to assess the kinetics of transmural response. Patients were subsequently followed long-term. The primary endpoint was transmural response, defined as a 25% decrease in IBUS-SAS at W4 and W12. Alternative definitions of transmural remission using the BUSS score or the us-C-score were also evaluated at W4 and W12. Secondary endpoints included clinical response and clinical remission according to PRO-2 (W4, W8, W12), biochemical response (change in fecal calprotectin), and transmural remission (normalization of ultrasound) (W4 and W12). Secondary long-term outcomes included treatment survival without discontinuation, hospitalization, progression of bowel damage, and surgery. Results A total of 101 patients were included, with a mean age of 42.9 ± 15.0 years, 58% women, and 45.9% active smokers. Montreal classification was as follows for disease location (L1 = 41% / L2 = 11% / L3 = 48%), phenotype (B1 = 28.9% / B2 = 42.1% / B3 = 28.9%), and prior perianal CD (37%). Among them, 44.9% had previously required intestinal resection. While 28% of patients had prior exposure to one biologic, 32% and 40% were exposed to two and ≥ 3 advanced therapies, respectively. Clinical response and clinical remission were observed in 57.7% and 33.9% at W4, 70.1% and 33.3% at W8, and 79.2% and 38.0% of patients at W12, respectively. Median fecal calprotectin levels were 269, 192, 200, and 135 µg/g at W0, W4, W8, and W12, respectively. Transmural response rates were 27.3% at W4 and 28.5% at W12 according to IBUS-SAS, 9.1% at W4 and 14.3% at W12 according to BUSS, and 52.3% at W4 and 54.3% at W12 according to the us-C-score. Transmural remission was achieved in 8.5% of patients at W12. Segmental transmural response did not differ between ileal and colorectal segments regardless of the scoring system used. Predictive factors of response and long-term outcomes will be available for the congress. Conclusion In this prospective multicenter study including unselected patients with Crohn’s disease previously exposed to at least one anti-TNF, risankizumab achieved early clinical, biochemical, and transmural effectiveness, supporting its use in this clinical situation. Conflict of interest: Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Mathieu, Kelly: No conflict of interest M’Baye, Diari: No conflict of interest Huet, Julie: No conflict of interest Ferrari, Tessa: No conflict of interest Yzet, Clara: No conflict of interest Guillo, Lucas: No conflict of interest Hupé, Marianne: No conflict of interest Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Pereira, Bruno: No conflict of interest Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda</p
Maurice Kleman et la physique des défauts. Une approche topologique toujours d’actualité
No full textInternational audienceLes défauts sont au coeur de l'oeuvre que nous a léguée Maurice Kleman. Il s’agit ici, au-delà des dislocations (voir glossaire) bien connues pour leur rôle dans la plasticité des solides, de défauts dans des organisations très diverses de la matière telles que les textures ferromagnétiques, les cristaux liquides, les phases lamellaires et les quasi-cristaux. De par sa généralité, l’approche topologique de Maurice Kleman a profondément renouvelé la physique des défauts dans de nombreux domaines de la matière condensée
Prognostic impact of late gadolinium enhancement granularity using cardiovascular magnetic resonance in end-stage hypertrophic cardiomyopathy
No full textInternational audienceBackground: End-stage hypertrophic cardiomyopathy (HCM) is a distinct and advanced form of HCM, defined by a left ventricular ejection fraction (LVEF) < 50% and associated with a markedly poor prognosis. Evidence on the prognostic relevance of LGE and its key features in end-stage HCM remains limited. We aim to evaluate the prognostic value of the LGE granularity model including its location, extent and pattern in end-stage HCM patients.Methods: All patients referred for cardiovascular magnetic resonance (CMR) assessment of HCM at three French university hospitals between 2008 and 2024 were retrospectively screened. All patients with HCM and LVEF < 50% were included. The “LGE granularity model” was defined as a model combining LGE extent (focal vs. multifocal involvement), location (septal vs. other), and pattern (subepicardial vs. midwall). The primary endpoint was all-cause mortality using the National Registry of Death.Results: Among 2,873 patients with HCM, 691 (24%) with end-stage HCM were included (53±7 years, 54% male). At the time of CMR, 30% of patients presented with heart failure symptoms classified as NYHA > II and 26% had a history of atrial fibrillation. After a median follow-up of 9 years (IQR 6–11), 226 patients died (32%). LGE was observed in 259 patients (37%) and was strongly associated with mortality (HR: 3.37, [95% CI: 2.57-4.42], p< 0.001), even after adjustment for traditional prognostic factors (HR: 1.52, [95% CI: 1.07-2.18], p=0.02). In sub-group analysis, LGE presence was associated with all-cause mortality in patients with LVEF >40% (HR: 3.32 [95% CI: 1.61-6.45], p< 0.001) but was not in patients with LVEF < 40% (HR: 0.98 [95% CI: 0.73-1.32], p=0.90). Each LGE granularity component was independently associated with mortality after adjustment with traditional prognostic factors: LGE extent (HR: 2.85, [95% CI: 1.03-7.85], p=0.02), septal location (HR: 1.73, [95% CI: 1.10-2.73], p< 0.001), and midwall pattern (HR: 4.15, [95% CI: 1.79-9.61], p< 0.001). The LGE granularity model improved risk reclassification and discrimination compared to traditional prognostic factors (NRI: 32%; IDI: 10%, both p< 0.001; global Chi-square: 139 to 167, p< 0.001).Conclusion: In this large multicenter cohort of end-stage HCM patients, the LGE granularity model integrating the LGE extent, location, and pattern provided strong and independent prognostic value beyond traditional prognostic factors
The clinical benefit of a near complete cytoreduction in patients with colorectal peritoneal metastases: a propensity score matched study
No full textInternational audienceBackground: Colorectal cancer with peritoneal metastases (PM) presents a significant therapeutic challenge. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one option to prolong survival. While completeness of cytoreduction (CC) score 0 is associated with improved outcomes, the clinical value of near-complete CC-score 1 versus open-close laparotomy (CC-3) remains unclear.Methods: This retrospective study evaluates overall survival (OS) in patients with colorectal cancer PM scheduled for CRS and HIPEC from 23 global peritoneal-surface oncology centers from 2006 to 2023. A propensity score matching was performed using tumor location (colon/rectum), lymph node status, liver metastases, signet-ring histology, preoperative chemotherapy, peritoneal cancer index, and treatment year. Matching was performed using the nearest neighbor method with a caliper of 0.1, chosen after several iterations to optimize intergroup balance. Balance was assessed using standardized mean differences. Sensitivity analyses with alternative calipers and multivariable Cox regression in the unmatched cohort were considered to test the robustness of the findings. The study time-period was divided into 4 equal quartiles for analysis.Results: In the unmatched cohort (n = 284), patients with CC-1 had significantly longer median OS compared to those with CC-3 (22.2 vs. 9.4 months, p < 0.001). After 1:1 matching (n = 172), the OS advantage of CC-1 persisted, with a median OS of 18.9 months (95 % CI: 14.2-24.7) versus 10.5 months (95 % CI: 9.4-12.3) for CC-3, p < 0.0001, HR 0.4 (95 % CI:0.27-0.56). Multivariable Cox regression confirmed CC-1 as a significant predictor of survival (HR: 0.15, 95 % CI: 0.08-0.26). The CC-1 proportion went from 55 to 65 % in time-periods 1 & 2-39 % in period 3, to 11 % in period 4; leading to significantly reduced survival rates in the latter time-periods 3 & 4.Discussion: Near complete cytoreduction is associated with improved overall survival compared to open-close laparotomy. Prospective or standardized multicenter analyses will be required to confirm the clinical value of a near complete cytoreduction
Juvenile-onset mixed connective tissue disease: A multicenter retrospective cohort study
No full textInternational audienceObjectives: Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMCTD, and compare them to adult-onset MCTD (aMCTD) patients. Methods: We conducted a multicenter, retrospective, case-control study within the French MCTD cohort. Each jMCTD patient was compared to 3 matched aMCTD patients. Results: Forty-seven jMCTD patients (93.6 % girls; median age at onset 14 [11-16] years) were included. Forty-four (93.6 %) jMCTD patients fulfilled either Sharp or Kasukawa diagnostic criteria. None of them met other diagnostic criteria without fulfilling Sharp or Kasukawa criteria. At diagnosis, jMCTD patients' main manifestations were Raynaud's phenomenon, arthralgia, and myalgia. jMCTD patients had less frequently puffy fingers than aMCTD (p < 0.0001). Cumulatively, jMCTD patients mainly received glucocorticoids (80.9 %), hydroxychloroquine (95.7 %) and immunosuppressants (93.6 %). They received a higher initial dose of glucocorticoids (30 [20-60] mg/day vs. 15 [10-35] mg/day, p = 0.02), and significantly more frequently methotrexate (Methotrexate) and rituximab (p = 0.01) over time compared to aMCTD. After a median follow-up of 9.8 [6.6-16.2] years, 29 (61.7 %) jMCTD patients were in remission (vs. 62 (44.0 %) aMCTD; p < 0.05), 36 % had progressed to another CTD (vs. 30.5 % aMCTD; p = 0.5), mainly systemic lupus erythematosus, 11 (23.4 %) had developed interstitial lung disease, 2 (4.3 %) pulmonary arterial hypertension, and 1 (2.1 %) died. Conclusions: jMCTD share the same clinical characteristics as aMCTD patients, but less frequently have puffy fingers. Outcomes appear more favorable in jMCTD than aMCTD, with higher remission rates, albeit at the cost of more intensive treatment
Multi-Scale Modeling of Enzymatic Hydrolysis Efficiency Based on Machine Learning: From Hydrothermal Pretreatment Conditions to Lignin Structural Properties
No full textInternational audienceThe increasing depletion of fossil resources and escalating environmental challenges highlight the urgent need for efficient utilization of lignocellulosic biomass.However, the inherent recalcitrance of lignocellulose hampers its enzymatic degradation and conversion efficiency, making pretreatment essential to improve enzyme accessibility and promote carbohydrate release. In this study, we developed predictive models of enzymatic hydrolysis based on hydrothermal pretreatment by integrating multidimensional features, including feedstock composition, process parameters, and pretreatment outcomes. Among multiple machine learning algorithms, XGBoost demonstrated superior performance across training, testing, and validation sets (R² = 0.994, 0.841, and 0.856, respectively). At the microscopic level, lignin was further examined as a key factor. The correlation models were established between lignin physicochemical properties, including molecular weight (Mw, Mn), interunit linkages (β-O-4, β-5), functional groups (phenolic, aliphatic, and carboxyl hydroxyl groups), and enzymatic conversion efficiency. XGBoost again demonstrated as the best model, which interpretability was enhanced using feature importance ranking, SHAP dependency analysis, and two-dimensional partial dependence plots (2D-PDP), revealing cross-scale, multidimensional mechanisms within the pretreatment system. By integrating macro-level regulation and micro-level mechanistic models, this study provided a systematic framework for understanding biomass hydrolysis and offers data-driven guidance for optimizing pretreatment strategies and improving conversion efficiency.</div