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Salvage of Failed Patellofemoral Arthroplasty Due to Instability: Combined Medial Patellofemoral Ligament Reconstruction, Tibial Tubercle Osteotomy, and Vastus Medialis Obliquus Advancement - Case Report and Algorithm-Based
No full textInternational audienceIntroduction/Objectives: Patellofemoral arthroplasty (PFA) is a joint-sparing alternative to total knee arthroplasty (TKA) for isolated patellofemoral osteoarthritis, offering symptom relief while preserving tibiofemoral compartments and bone stock compared with TKA, particularly in younger and active patients. However, persistent anterior knee pain and patellar instability remain leading causes of early failure, even when prosthetic components are stable and tibiofemoral degeneration is absent. This study aimed to describe a combined, non-prosthetic surgical strategy for symptomatic PFA failure due to patellar instability and to propose an algorithm-based framework for clinical decision-making. Methods: A 54-year-old woman presented with chronic anterior knee pain and recurrent instability four years after isolated PFA. Imaging confirmed stable and well-aligned prosthetic components with preserved tibiofemoral compartments but consistent lateral patellar subluxation. The patient was treated using a joint-preserving approach combining medial patellofemoral ligament (MPFL) reconstruction with hamstring autograft, anteromedial tibial tubercle osteotomy, and vastus medialis obliquus (VMO) advancement. Clinical outcomes were assessed with the Kujala and International Knee Documentation Committee (IKDC) scores at six weeks and three months. Results:At three months, the Kujala score improved from 54 to 78, and the IKDC subjective score increased from 38 to 69. The patient reported significant pain reduction, restoration of patellar stability, and functional recovery. No recurrent instability, surgical complications, or implant-related problems were observed. Radiographs confirmed correct alignment and congruent prosthetic components.Conclusion:A combined approach addressing soft-tissue, bony, and dynamic stabilizers may provide an effective, joint-preserving alternative to total knee arthroplasty in selected patients with symptomatic PFA failure caused by instability. The algorithm presented may assist in surgical decision-making and optimize patient outcomes
Phase I(b) study evaluating the safety and efficacy of intratumoral agonistic anti-CD40 (selicrelumab) in combination with anti-PD-L1 (atezolizumab) in patients with refractory or relapsed B-cell lymphoma (ITSELF trial)
No full textInternational audienceBACKGROUND: The efficacy of immune checkpoint blockade therapy requires pre-existing antitumor immunity. Defective antigen presentation during the priming phase can reduce the generation of tumor-specific T cells, which are necessary during the effector phase and subsequent tumor elimination. We propose an in situ immunization strategy to enhance direct tumor antigen presentation by the lymphoma B cells via cluster of differentiation (CD)40 stimulation in order to sensitize B-cell lymphoma to programmed cell death protein 1/programmed death-ligand 1 (PD-L1) blockade therapy.MATERIALS AND METHODS: ITSELF is a multicenter, open-label, dose-escalation phase Ib trial of intratumoral selicrelumab, an agonistic anti-CD40 monoclonal antibody, every 3 weeks for three cycles in combination with intravenous atezolizumab, an antagonistic anti-PD-L1 monoclonal antibody, at 1200 mg every 3 weeks for three cycles followed by intravenous atezolizumab monotherapy for a total of 12 months in patients with relapsed/refractory B-cell lymphoma. RESULTS: Two patients with follicular lymphoma and two patients with diffuse large B-cell lymphoma were enrolled at the first dose level of 1 mg intratumoral selicrelumab. Those four patients received the three cycles of intratumoral selicrelumab in combination with intravenous atezolizumab. Patients did not develop severe adverse events related to the drugs or the intratumoral procedures. No or low-grade adverse events were reported and related to atezolizumab or to the combination therapy. All patients discontinued the treatment because of disease progression according to Lugano 2014 criteria on their first positron emission tomography scan disease evaluation at the end of cycle 3 (week 9). The trial was stopped prematurely because of issues with selicrelumab drug supply.CONCLUSION: The combination of 1 mg of intratumoral selicrelumab and 1200 mg of intravenous atezolizumab was safe for patients with relapsed/refractory B-cell lymphoma and led to some tumor stabilization or regression, although it did not result in objective tumor response
Ischemia-Reperfusion Dynamics in Acute Myocardial Infarction Experimental Swine Model: New Insights from Quantitative CMR
No full textInternational audienceAims To reveal the pattern and dynamics of myocardial edema induced by myocardial infarction (MI) during ischemia and subsequent reperfusion, that remain largely unknown, as are the factors that contribute to reperfusion injury. To propose a time-resolved dynamic myocardial tissue characterization by quantitative CMR, with T1&T2 mapping and Pixel-wise standardized analysis to circumvent inter-animal differences and subjective ROI positioning. Methods and Results We measured T1&T2 relaxation times at baseline, during a 40-minutes transient coronary occlusion, and after reperfusion in an open-chest swine MI model (n=20; 2 shams) using MRI. Myocardial function, early and late gadolinium enhancement were also assessed. Pixel-wise standardized analysis was used to compare the image contents at each pixel across individuals and time points. A significant increase in cardiac T1&T2 times in the ischemic regions occurred during ischemia compared to baseline (mean ΔT1=118.8ms i.e. +11.1%, ΔT2=5.6ms i.e. +11.3%; p<0.05). A global significant and marked increase in T1&T2 times further appeared immediately after reperfusion (mean ΔT1=256.8ms i.e. +23.3% mean ΔT2=11.9ms i.e. +23.6%, p<0.001). This increase was associated with myocardial wall thickness changes, with regional and global dysfunction in the ischemic myocardium. Three different reperfusion patterns were differentiated by the pixel-wise T1 signal analysis: effective reperfusion with microvascular obstruction (MVO), effective reperfusion without MVO and absence of effective reperfusion. We found no correlations between baseline, per-ischemia, and post-reperfusion native T1&T2 times when effective reperfusion occurred. Conclusions Objective quantification of tissue response by pixel-wise analysis demonstrated rapid and significant changes in myocardial water content status post-reperfusion, with three different early-reperfusion patterns observed, suggesting distinct reperfusion mechanisms. The water content after reperfusion does not reflect its state before and it does not provide insight into the final tissue status observed within 3 hours after recanalization
SpeckSeq enables high-throughput functional stratification of MEFV variants in autoinflammatory diseases
No full textInternational audienceVariants of uncertain significance (VUS) are a major obstacle in genetic diagnosis, particularly when involving gain-of-function (GoF) mutations that are poorly predicted in silico. MEFV, which encodes the inflammasome sensor pyrin, is mutated in two autoinflammatory diseases, familial Mediterranean fever (FMF) and pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Here, we developed SpeckSeq, a method that combines DNA bar-coding, ASC speck–based single-cell sorting and next-generation sequencing to systematically identify hypermorphic MEFV variants in response to different stimuli. SpeckSeq identified 49 GoF mutations separated into two distinct groups containing either PAAND variants or FMF variants. SpeckSeq was validated using patients’ cells and supported a reclassification of MEFV variant pathogenicity, leading to novel diagnoses. As a large-scale mutagenesis approach, using human genetics as a guide, SpeckSeq revealed structural and functional pyrin features, including a putative ligand-accommodating cavity in the B30.2 domain. Altogether, SpeckSeq classifies VUS to refine molecular diagnostics and improve our knowledge on the pyrin inflammasome
Acceleration of implicit schemes for large systems of delay differential equations
No full textInternational audienceThe objective is to accelerate numerical implicit schemes for solving large linear or nonlinear delay differential equations. These schemes require solving large linear or nonlinear systems at each integration step, making effective initial guesses critical for rapid convergence. For nonlinear problems, an inexact Newton method is used, whose efficiency depends heavily on the quality of these initial guesses. To generate them, line search or trust-region algorithms are employed -each involving the solution of large linear systems. These linear systems are solved using a Krylov subspace method. Initial guesses are constructed via a Petrov-Galerkin process applied to low-dimensional approximation subspaces derived from previous steps. Error estimates are provided, linking the accuracy of the initial guesses to the timestep size, the scheme's order, and the subspace dimension. Numerical experiments show speedups of up to two orders of magnitude over standard predictor-based methods, when those converge
Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis
No full textInternational audienceBackground: Target trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.Methods: This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the Observatoire Français de la Sclérose en Plaques (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment.Results: 14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions.Conclusion: The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS
In vitro comparison of biological properties of CoCr, Ti-6Al-4V, and PEEK for removable partial denture
No full textInternational audienceAbstractStatement of problem : To address the limited biocompatibility of conventional removable dental prostheses (RDPs), new materials and manufacturing techniques are being actively investigated.Purpose : This in vitro study aimed to evaluate and compare the biological response of human fibroblast (HGF) to cobalt-chrome (Co-Cr), titanium alloy (Ti), and polyetheretherketone (PEEK), fabricated via tree distinct methods: casting, selective laser melting (SLM) and machining.Material and methods: The surface chemical composition and the wettability of cast Co-Cr, SLM Co-Cr, SLM Ti, machined Ti, and PEEK were assessed. HGF were cultured in contact with material extracts, and all assays were conducted following this exposure. Ion release was assessed using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and pH measurement. Surface roughness was subsequently measured on each sample. Cell viability was assessed using the Live/Dead staining, while metabolic activity was evaluated using the Alamar Blue assay. Cell morphology was observed by scanning electron microscopy (SEM) and confocal microscopy, while inflammatory profile was assessed using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using one-way ANOVA and Tukey’s test (p < 0.05 and 0.001).Results: SLM Co-Cr exhibited higher Co and Cr surface content than cast Co-Cr, while SLM Ti showed a reduced titanium content and increased aluminum content relative to machined Ti. Among all tested materials, machined Ti demonstrated the highest surface wettability, evidenced by a significantly lower contact angle (p < 0.001). HGF exposed to extracts of machined Ti and PEEK exhibited greater cell viability and metabolic activity, comparable to the control group. In contrast, cast Co-Cr was associated with significantly increased IL-6 secretion, although TNF-α and IL-10 levels remained stable across tested groups.Conclusions: Machined titanium (Ti) and PEEK exhibited favorable in vitro biocompatibility, with high cell viability, enhanced cellular adhesion, and no significant cytotoxicity under our experimental conditions. These findings suggest that both materials may represent promising alternatives to CoCr alloys for the fabrication of removable partial dentures, although their clinical application requires further validation of their mechanical, physical, and long-term properties
Mechanical and microstructural characterization of the human tunica albuginea
No full textInternational audienceThe tunica albuginea (TA) is a fibrous connective membrane surrounding the corpora cavernosa (CC), which plays a crucial role in the erection. In case of erectile dysfunction, inflatable penile prothesis (IPP) may be a treatment of choice and mechanical interactions occur between prostheses and these penile tissues. There is still much to be learned about their mechanical behavior to help to improve IPP and penile surgical techniques. This paper presents the characterization of the TA mechanical behavior combined with the observation of its microstructural organization, as well as the mechanical behavior of the cavernous tissue. Uniaxial tensile tests were performed on 40 TA samples and 17 CC samples collected from 5 post mortem human subjects. TA samples were cut along both longitudinal and circumferential directions, and in both proximal and distal regions. Histological slices were produced from biopsies contiguous to the samples to observe the collagen fiber organization in the TA. We observed that this fiber organization usually schematized by 2 layers of perpendicular fibers is more complex, with some dispersion in the fiber orientations and interlacing of the 2 layers. The mechanical characterization of the TA samples revealed no clear anisotropy but different properties for the proximal and distal locations, whereas the CC showed a very low elastic modulus. These data complement those already published and further analysis of the microstructure of the TA will be needed to explain the variability of the mechanical behavior of the TA in view of selecting and identifying nonlinear behavior models
Large B-cell lymphoma: The LYSA pragmatic guidelines
No full textInternational audienceThe management of large B-cell lymphomas (LBCL) has undergone major changes over the last 5 years. These changes reflect the availability of new therapies (immunotherapies, cell therapies, targeted molecules), but also a better compartmentalization of the entities and their specific clinical characteristics. Numerous first-, second- and third-line therapeutic strategies are available, and each practitioner is committed to selecting the treatment that offers the best balance between efficacy and toxicity. Advances in the understanding of LBCL biology, coupled with improvements in diagnostic and monitoring tools and therapeutic approaches, have significantly enhanced patient outcomes in recent years. In this article, we present a set of pragmatic guidelines developed by the LYSA (Lymphoma Study Association) for the management of LBCL. These guidelines address key aspects of diagnosis, staging, response evaluation, and treatment, integrating the latest evidence from clinical trials, expert consensus, and real-world practice. They aim to provide clinicians with a clear, practical framework to optimize care for patients with LBCL, ensuring that the best available evidence is translated into clinical practice
Preoperative flexion contracture does not impair outcomes or early revision rates following robotic total knee arthroplasty with functional alignment
No full textInternational audienceAbstract Purpose Preoperative flexion contracture remains a challenging deformity in total knee arthroplasty (TKA). This study aimed to evaluate whether the presence of preoperative flexion contracture influences outcomes and early revision rates following robotic‐assisted TKA performed with functional alignment (FA) principles. Methods This retrospective comparative study analysed 190 patients who underwent robotic‐assisted TKA using a computed tomography‐based FA strategy. Patients were grouped based on intraoperative measurement of flexion contracture: ≥10° (study group; 43 patients) and <10° (control group; 147 patients). Clinical outcomes, intraoperative data, and early revision rates were assessed at a minimum 24‐month follow‐up. Results The study group exhibited significantly more varus alignment intraoperatively and required greater lateral tibial and posterior medial femoral resections. Preoperative knee flexion was lower in the contracture group (110° vs. 120°, p = 0.0018), and postoperative flexion remained slightly reduced (120° vs. 130°, p = 0.05). Flexion contracture at follow‐up was 1° in the study group versus 0° in controls ( p = 0.04). However, no significant differences were observed in Knee Society Scores, Forgotten Joint Score, Kujala score, or early revision rates. All‐cause revision rates were similar (97.67% vs. 98.64%, p = 0.66), with a hazard ratio of 1.85 (95% CI: 0.12–27.72). Aseptic survivorship was 100% in the contracture group versus 99.32% in controls ( p = 0.59). Conclusion Patients with preoperative flexion contracture ≥ 10° achieved comparable mid‐term outcomes and early survivorship to those without contracture following robotic‐assisted TKA using FA. These findings support FA as a reliable strategy to manage complex deformities without the need for soft tissue releases. Level of Evidence Level III