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Induction of haemodynamic travelling waves by glial-related vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging
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CADOR (Capsaicin in neuropathic-like pain in digital osteoarthritis) study protocol: a multicentre randomised parallel-group trial
No full textInternational audienceIntroduction It is common for finger pain in hand osteoarthritis (HOA) to display a neuropathic component. Non-steroidal anti-inflammatory drugs (NSAIDs) and conventional analgesics are not very effective in relieving this neuropathic-like pain. Capsaicin, a compound extracted from chilli peppers, is approved for the management of localised neuropathic pain. However, the effectiveness of an 8% capsaicin transdermal patch has never been tested in HOA patients with neuropathic-like pain in a randomised setting. In this study, we aimed to compare the 60-day (D60) efficacy of a transdermal application of capsaicin 8% versus a control (very low-dose capsaicin at 0.04%) on hand pain in patients with painful digital osteoarthritis with a neuropathic-like pain component. Methods and analysis CADOR (CApsaicin in neuropathic-like pain in Digital Osteoarthritis: a Randomised trial) is a multicentre, randomised, controlled, double-blind, two parallel group, phase 3 clinical trial. Eligible patients have HOA according to the American College of Rheumatology criteria and at least Kellgren-Lawrence grade≥2, with neuropathic-like pain (‘Douleur neuropathique en 4 questions’ (DN4) score≥4/10 and pain intensity≥40/100 mm). At Day 0, 120 patients will be randomised (1:1) to receive a single 30 min topical application of either capsaicin 8% transdermal patch (experimental group) or capsaicin 0.04% transdermal patch (control group). The primary outcome is pain intensity in the fingers over the past 48 hours at Day 60, measured with a Visual Analogue Scale (VAS) ranging from 0 to 100 mm. Secondary outcomes are functional disability, quality of life, anxiety and depression, the patient’s global impression of improvement, use of analgesics and NSAIDs and the safety of capsaicin. At visit D60, patients who still have finger pain≥40/100 mm on the VAS will receive, if they wish a single 30 min topical application of capsaicin 8% transdermal patch (not blinded). The efficacy of two transdermal applications of capsaicin (either two applications of 8% patch in the experimental arm or one application of 0.04% and one application of 8% in the control arm) will be assessed on Day 120. Ethics and dissemination Ethics approval was obtained from the French Health Authorities (Comité de protection des Personnes SUD EST V and Agence Nationale de Sécurité du Médicament) on 23 May 2024 in accordance with European Regulation n°536/2014 of 16 April 2014 (ref: 2024-511159-16-00) before participant enrolment. Trial registration number ClinicalTrials.gov: NCT06444919
Skin Fibroblasts from Individuals Self-Diagnosed as Electrosensitive Reveal Two Distinct Subsets with Delayed Nucleoshuttling of the ATM Protein in Common
No full textInternational audienceElectromagnetic hyper-sensitivity (EHS) and its causal link with radio-frequencies raise a major question of public health. In the frame of the clinical study DEMETER, 26 adult volunteers self-diagnosed as EHS-positive agreed to reply to a self-assessment questionnaire and to provide a skin biopsy sampling to establish a primary fibroblast cell line. The questionnaire and the biological data revealed, independently, 2 subsets of donors associated each with a low background, highly responsive (LBHR) and a high background, lowly responsive (HBLR) phenotype. A couple of subsets based on questionnaire data and based on the yield of spontaneous DNA double-strand breaks were found to be composed of the same donors at 64% identity. After exposure to X-rays, and application of anti-γH2AX, pATM, and MRE11 immunofluorescence, all the DEMETER fibroblasts (26/26) elicited a delayed radiation-induced ATM nucleoshuttling (RIANS). The use of RIANS biomarkers showed that the 2 phenotypes described above corresponded to DEMETER donors with a high risk of cancer (LBHR) or high risk of accelerated aging (HBLR). By exposing DEMETER cells to H2O2 followed by an antioxidative agent, we confirmed that EHS may be related to the management of DNA strand breaks. A preliminary molecular model of EHS inspired by the RIANS model was proposed
Study protocol and statistical plan for the ICRAKI trial: Intermittent haemodialysis versus continuous renal replacement therapy for severe acute kidney injury in critically ill patients
No full textInternational audienceBackground: The effect of intermittent haemodialysis (IHD) vs continuous renal replacement therapy (CRRT) on mortality and/or renal function recovery in adults with acute kidney injury (AKI) and a recognised indication for renal replacement therapy (RRT) remains controversial.Objective: To summarise the protocol and statistical analysis plan for the ICRAKI trial.Design, settings and participantsICRAKI is a non-inferiority multicentre randomised controlled trial comparing IHD and CRRT. We will include 1000 patients with AKI receiving (or who have received) invasive mechanical ventilation and/or catecholamine infusion and who have at least one recognised criterion for initiating RRT.Intervention: The study compares IHD with CRRT.Main outcomes measures: The primary endpoint is the proportion of patients who will meet one or more criteria for a major adverse kidney event (composite of death, RRT dependence and/or more than a 25 % increase in serum creatinine from baseline value) 90 days after randomisation. Secondary endpoints are time to death; mortality at day (D)28, D60 and D90; number of patients with RRT dependency at D28, D60 and D90; number of patients with more than a 25 % increase in serum creatinine from baseline value at D28, D60 and D90; intensive care unit (ICU) and hospital length of stay; time until cessation of RRT; catecholamine-free days, ventilator-free days and RRT-free days through day 28; estimated glomerular filtration rate at hospital discharge; the number of episodes of adverse events.Conclusion: The ICRAKI trial will inform the choice of RRT modalities in critically ill patients with severe AKI. More than 300 patients were already included
Developing Cancer Quality of Care Indicators to Quantify the Impact of a Global Destabilization of the Care System (COLLAT-COVID)
No full textInternational audienceBackground/Objectives: The COVID-19 pandemic led to significant disruptions in healthcare systems, particularly impacting cancer care through delays in diagnoses and treatments. Quality indicators (QIs) are essential tools for monitoring healthcare performance, yet existing QIs may not be suited for crises. This study aimed to develop a set of hospital-based QIs tailored to assess the impact of care reorganization during health crises across four cancer types: breast cancer, hepatocellular carcinoma, gynecological cancers (excluding ovarian cancer), and peritoneal carcinomatosis. Methods: A multidisciplinary steering committee (SC) conducted a five-stage process, including a literature review, indicator selection, content validation via the RAND/UCLA method, final validation by the SC, and a pilot feasibility study. QIs were assessed based on clinical relevance, reproducibility, sensitivity to change, and feasibility. Expert panels evaluated and validated the indicators in two rounds of voting. Results: Among 150 initially identified QIs, 49 were validated: 12 for breast cancer, 11 for hepatocellular carcinoma, 8 for gynecological cancers, and 18 for peritoneal carcinomatosis. Most (92%) were process indicators, covering diagnosis, treatment, and care delays. Two common indicators were identified across all four cancers: multidisciplinary team meeting discussions and psychological support consultations. Conclusions: This study demonstrates the feasibility of developing crisis-responsive QIs to monitor cancer care during health system disruptions. Future work will focus on their real-time implementation, validation in international settings, and integration into healthcare policies to enhance crisis preparedness
Surgical Mitral Valve Repair vs Replacement After Failed Mitral Transcatheter Edge-to-Edge Repair: The CUTTING-EDGE Registry
No full textInternational audienceBACKGROUND: The impact of mitral valve (MV) surgery type after failed mitral transcatheter edge-to-edge repair (M-TEER) has not been well studied. OBJECTIVES: The aim of this study was to compare the outcomes of MV repair vs replacement after failed M-TEER. METHODS: From 2009 to 2020, a total of 332 patients across 34 centers from the CUTTING-EDGE registry underwent MV surgery after M-TEER. Outcomes were compared between MV repair and replacement. Primary outcomes included 30-day mortality and 1-year survival after MV surgery. RESULTS: Among enrolled patients (mean age 73.8 ± 10.1 years, median Society of Thoracic Surgeons Predicted Risk of Mortality 3.9% [Q1-Q3: 2.2%-6.8%]), 25 (7.5%) underwent repair and 307 (92.5%) underwent replacement. The replacement group had a significantly higher rate of comorbidities, including atrial fibrillation, prior cardiac surgery, more secondary mitral regurgitation, and more devices implanted at index M-TEER (P < 0.05 for all). Replacement patients showed a trend toward higher 30-day mortality (17.7% [52 of 294] vs 4.0% [1 of 25]; P = 0.094). The observed-to-expected ratio of 30-day mortality was 3.6 (95% CI: 1.9-5.3) overall, 3.8 (95% CI: 2.1-5.5) in the replacement group, and 1.7 (95% CI: 0.7-3.3) in the repair group. Replacement patients had higher 1-year mortality (33.3% [65 of 195] vs 10.5% [2 of 19]; P = 0.041). Significantly lower survival rates were observed after replacement at 2 years (P = 0.033) and persisted in the risk-adjusted Cox regression analysis (HR for replacement: 4.24; 95% CI: 1.04-17.31; P = 0.044). CONCLUSIONS: MV surgery after failed M-TEER is a high-risk procedure associated with higher than expected 30-day mortality, with higher mortality associated with MV replacement. Compared with repair, replacement is associated with higher 1-year mortality and a lower 2-year survival
Evaluation of a deep learning segmentation tool to help detect spinal cord lesions from combined T2 and STIR acquisitions in people with multiple sclerosis
No full textInternational audienceObjective: To develop a deep learning (DL) model for the detection of spinal cord (SC) multiple sclerosis (MS) lesions from both sagittal T2 and short tau inversion recovery (STIR) sequences and to investigate whether such a model could improve the performance of clinicians in detecting SC lesions.Materials and methods: A DL tool was developed based on SC sagittal T2 and STIR acquisitions from the imaging database of the French MS registry (OFSEP), including retrospective data from 40 different scanners. A multi-reader study based on retrospective data was performed between December 2023 and June 2024 to compare the performance of 20 clinicians in interpreting upper and lower SC acquisitions with and without the use of the tool. A ground truth was established by three experts. Sensitivity, precision, and inter-reader variability were evaluated.Results: We included 50 patients (39 females, median age: 41 years [range: 15-67]) with SC MRI acquired between February 2017 and December 2022. When reading with the tool, the clinicians' mean sensitivity to detect SC lesions improved (from 74.3% [95% CI = 67.8-80.6%] to 79.2% [95% CI: 73.5-85.0%]; p < 0.0001), with no evidence of difference in the mean precision: (69.0% [95% CI: 62.8-75.2%] vs 70.1% [95% CI: 64.3-75.9%]; p = 0.08). Inter-reader variability in lesion detection was slightly improved with the tool (Light's kappa = 0.55 vs 0.60), but without statistical difference (p = 0.056).Conclusion: The use of an automatic tool can help clinicians detect SC lesions in pwMS by increasing their sensitivity.Key points: Question No tool to help detect MS SC lesions is used in clinical practice despite their frequency and prognostic value. Findings This DL-based tool led to improvement in clinicians' sensitivity in detecting SC lesions from both sagittal T2 and STIR sequences, without decreasing precision. Clinical relevance Our study indicated the potential of a DL-based tool to assist clinicians in the challenging task of detecting SC lesions in people with MS on a combination of sequences commonly acquired in clinical practice
Myeloid Neoplasms With Erythroid Predominance and Excess Blasts in Young Adults Exhibit Distinct Genetic Profiles
No full textInternational audienceThe evolution of acute myeloid leukemia (AML) classifications has progressively shifted the diagnostic focus toward genetic criteria. Nevertheless, morphology remains a key element in clinical practice, often serving as the initial trigger for additional molecular investigations. The diagnosis of acute erythroleukemia (AEML), initially defined by the FAB group, is no longer recognized as a distinct entity in the latest WHO and ICC classifications. Some studies have indicated that AEML shares similarities with myelodysplastic neoplasms, including a high frequency of TP53 mutations and adverse karyotypes. Here, we conducted a retrospective analysis in adults with AEML defined using historical morphologic criteria (≥ 50% erythroid precursors and ≥ 20% blasts among non‐erythroid cells). In contrast to older patients, young adults (18–60 years) exhibit unique genetic profiles including a high prevalence of normal karyotypes (65%), NPM1 (35%) and UBTF (23%) mutations. AEML morphology in NPM1 ‐mutated cases did not impact clinical outcomes but was associated with specific molecular features, including an enrichment of WT1 and cohesin gene mutations. In this age group, our findings support that morphologically defined AEML often corresponds to AML according to current genetic criteria, consistent with recent classification systems that prioritize molecular features over morphology
Response to systemic treatments and survival of fibrolamellar carcinomas: An AGEO-SFCE French multicenter retrospective cohort
No full textInternational audienceIntroductionFibrolamellar carcinomas (FLC) are rare and predominantly advanced hepatic malignancies, lacking a clear consensus on anti-tumor treatments (ATT). The primary objective of the study was to determine whether any ATT appeared to give favorable outcomes in terms of morphological objective response (ORR) and disease control (DCR) rate according to RECIST 1.1 criteria.Patients and methodsThis retrospective multicentric French cohort from 14 centers included 44 patients with histologically proven FLC who received at least one ATT (chemotherapy and/or tyrosine kinase inhibitors, TKI) and underwent at least one morphological evaluation. .ResultsA total of 40 anti-tumor responses were analyzed after a first line treatment. No complete response was observed, with an ORR in 13 % of cases, a DCR in 55 % of cases and 45 % of disease progression. GEMOX regimen (n = 9) showed an ORR of 11 % and a DCR of 33 %; the combination of doxorubicin and platinum-based chemotherapy (n = 6) achieved an ORR of 33 % and a DCR of 83 %. For TKI, sorafenib (n = 10) and sunitinib (n = 3), there was no objective response, with a DCR of 40 % and 33 % respectively. The median and the 5-years overall survival were 3.3 years and 35 % (95 %CI=[0.23–0.54]) respectively.ConclusionFLC have a poor prognosis; ATT show mild response rate. Further approaches and personalized medicine seem to be an unmet need for patients with FLC and new treatments should be urgently developed
T cell malignancies after CAR T cell therapy in the DESCAR-T registry
No full textInternational audienceThe risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.8%) received axicabtagene ciloleucel, 205 (6.7%) brexucabtagene autoleucel, 44 (1.4%) lisocabtagene maraleucel and 769 (25.1%) tisagenlecleucel. All multiple myeloma patients received idecabtagene vicleucel, with none receiving ciltacabtagene autoleucel. After a median follow-up of 12.7 months for B cell lymphoma, 17.7 months for B cell ALL and 6.3 months for multiple myeloma, only one (0.03%) patient developed a T cell malignancy after CAR T infusion. Specifically, the patient was diagnosed with a primary cutaneous CD30+ T cell lymphoproliferative disorder (anaplastic lymphoma kinase-negative) 3 years after receiving tisagenlecleucel therapy for diffuse large B cell lymphoma. This was associated with the integration of a CAR clone into the tumor suppressor gene PLAAT4 (phospholipase A and acyltransferase 4). Thus, the development of this secondary T cell malignancy might be linked to the use of CAR T cell therapy. In conclusion, our findings indicate a very low risk of T cell malignancy after CAR T cell therapy