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Nephrotic Syndrome Thromboprophylaxis With Direct Oral Anticoagulants or Vitamin K Antagonists
No full textInternational audienceIntroduction: Nephrotic syndrome (NS) is a pathological state of the glomerular filtration barrier associated with an increased venous and arterial thrombotic risk. Current guidelines suggest heparin-based or vitamin K antagonist (VKA) regimens for thromboprophylaxis in such patients. Although widely prescribed for other indications, direct oral anticoagulants (DOACs) are not recommended in NS because of limited pharmacological and safety reports. This study aimed to compare DOACs and VKAs for thromboprophylaxis in NS, specifically regarding thrombotic events (TEs) and bleeding events (BEs).Methods: We conducted a retrospective monocentric analysis of recorded NS episodes that required prophylactic anticoagulation between January 2006 and December 2023. We included 133 NS episodes of which 51 were treated with DOACs and 82 with VKAs. The primary endpoint was a composite endpoint, including thrombosis occurrence and major or clinically significant BEs during thromboprophylaxis. The secondary endpoints consisted of relevant features potentially involved when each primary endpoint was considered independently.Results: Patient characteristics, underlying NS etiology, personal thrombotic and bleeding risk factors, and biological parameters were globally similar in both groups. The primary endpoint appeared similar in both groups (P = 0.481). The secondary endpoints were mostly hypothesis-generating because of the low TE (n = 2) and BE (n= 7) occurrences.Conclusion: This study provides reassuring clinical data on DOAC use in NS thromboprophylaxis compared with VKAs, the recommended therapy, and calls for confirmation in randomized controlled trials (RCTs) and larger pharmacological studies.</div
Splenectomy during cytoreductive surgery in advanced epithelial ovarian cancer can be predicted
No full textInternational audienceIntroduction: Splenectomy may be necessary for complete cytoreductive surgery (CRS) in advanced stage epithelial ovarian cancer (AS-EOC), potentially raising perioperative morbidity and necessitating specific patient management. Objective: This study aimed to develop a predictive score of splenectomy in CRS of AS-EOC. Materials and methods: Data from histologically confirmed AS-EOC (FIGO IIB-IV) before CRS and diagnosed between 01/01/2000 and 01/06/2017, were extracted from the FRANCOGYN multicentric database (14 French hospitals). After identifying predictive factors of splenectomy, we performed a logistic regression to develop a prediction model and construct a risk score, allowing identification of a high-risk group. Model discrimination was assessed using a Receiver Operating Characteristic (ROC) curve. Decision Curve Analysis (DCA) was then conducted to evaluate the model's net clinical benefit across a range of threshold probabilities. Results: Among 1288 patients included, 7 % (n = 91) underwent splenectomy. Four independent variables statistically associated with splenectomy were identified: age <60 years (aDOR = 1.76, 95 % CI [1.13-2.75], p = 0.015), omental cake (aDOR = 2.12, 95 % CI [1.11-4.08], p = 0.024), diaphragmatic carcinosis (aDOR = 2.36, 95 % CI [1.34-4.18], p = 0.001), and digestive involvement at initial CT and/or laparoscopy (aDOR = 3.24, 95 % CI [1.93-5.43], p < 0.001). The ROC-AUC of this prediction model was 0.76. Patients meeting all 4 criteria with a maximum of 10 points defined the high-risk group and had a splenectomy probability of 32 % (95 % CI [22.00-44.31]), with a specificity of 95.8 % (95 % CI [94.5-96.9]) and a positive likelihood ratio of 6.31 (95 % CI [4.08-9.78]). The DCA showed a positive net clinical benefit of the model between 15 % and 40 % threshold probabilities. Conclusion: Using a simple 4-variable predictive score, patients at high risk of splenectomy during CRS in AS-EOC could be identified to improve patients' preoperative information and perioperative management
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
Allogeneic umbilical cord-derived mesenchymal stromal cells as treatment for systemic lupus erythematosus: a single-centre, open-label, dose-escalation, phase 1 study
No full textInternational audienceBackground: Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE.Methods: This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 106, 2 × 106, or 4 × 106 umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 106 cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29.Findings: From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 106 dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 106 cells per kg (range 2 × 106 to 4 × 106). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse.Interpretation: Our results suggest that a single infusion of 2 × 106 cells per kg or 4 × 106 cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to confirm clinical efficacy and the role of B-cell modifications in clinical benefit.ClinicalTrials.gov/NCT03562065 https://clinicaltrials.gov/study/NCT0356206
Mental distress or psychiatric condition? Exploring the gray area of categorizing psychological suffering among adolescents with obesity: a mixed methods study
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Outcome of high-grade B-cell lymphoma compared to other large B-cell lymphoma after CAR-T rescue. A DESCAR-T LYSA study
No full textInternational audienceHigh-grade-B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double hit [HGBL-DH] or triple hit [HGBL-TH]), or not otherwise specified (HGBL-NOS), are considered to be more aggressive diseases among large B-cell lymphomas (LBCL). CD19-targeting Chimeric Antigen Receptor (CAR) T-cells have changed the prognosis of chemoresistant LBCL. Clinical and pathological data of patients treated for relapsed/refractory LBCL or HGBL in third line or more, all characterized by FISH, were collected from the French DESCAR-T registry. Between January 2018 and November 2022, 228 patients were included across 14 centers, 73 with HGBL (28 HGBL-DH MYC-BCL2, 14 HGBL-TH, 8 HGBL-DH MYC-BCL6, 23 HGBL-NOS) and 155 with non-HGBL. Median follow-up was 18.5 months [95% CI, 14.3-23.4] from the date of infusion. Progression-free survival (PFS) and overall survival (OS) were not significantly different between HGBL and non-HGBL, at respectively 3.2 months [95% CI, 2.8-6.0] vs 4.5 months [95% CI, 3.1-8.7] (p = 0.103) and 15.4 months [95% CI, 5.6-32.4] vs 18.3 months [95% CI, 8.5-NR]. From the date of eligibility, the median OS was inferior for patients with HGBL-TH/DH MYC-BCL2 at 6.6 months vs 18.5 months for HGBL-NOS vs 13.6 months for HGBL-DH MYC-BCL6 vs 11.8 months for LBCL (p = 0.037). However, infused patients presented the same outcome. CAR T-cell therapy used in third line or more seems to overcome the poor prognosis of HGBL subtypes, especially in HGBL-TH/DH MYC-BCL2. This observation supports considering the potential benefit of using CAR-T earlier in the course of the disease
Diagnosis of subarachnoid haemorrhage: It is time to use spectrophotometry
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Assessing the Risk of Relapse After In Vitro Fertilization in Women With Multiple Sclerosis
No full textInternational audienceBackground and objectives: Older studies reported an increased risk of relapse after in vitro fertilization (IVF) in women with multiple sclerosis (MS), which has not been confirmed by more recent works. All these studies had several limitations, such as small sample sizes, absence of a control population, or lack of neurologic validation of the relapses. The aim of this study was to determine the risk of relapse after IVF in women with MS.Methods: This retrospective cohort study included all women with MS who underwent IVF between 2009 and 2019 and a control group of women with MS who did not undergo IVF matched on age, MS duration, number of relapses, and MS-specific treatments in the previous year. Data on MS (disease duration, treatments, and relapses) were from the French MS Registry (OFSEP), whereas data on IVF (number of procedures, stimulation protocol type, and outcomes) were from the French national health insurance database. For this, the 2 databases were linked by indirect matching.Results: In total, 115 women with MS underwent 199 IVF procedures (mean age at first IVF: 33.9 ± 4.0 years; 45.2% had ≥2 IVF procedures), and 175 IVFs (88.0%) could be matched to specific patients. The risk of relapse in the 3 months after index date was the same in both IVF group and control group (0.06 relapse per patient-year), as confirmed also by the before-after analysis in the IVF group (0.06 vs 0.08).Discussion: This study, using a 10-year clinical and administrative dataset, did not find any increased risk of relapse after IVF. The maintenance of disease-modifying therapies until IVF was a determining factor in reducing the risk of relapse
A French multicenter analytical evaluation of the automated Lumipulse G sNfL blood assay (Fujirebio®) and its comparison to four other immunoassays for serum neurofilament light chain assessment in clinical settings
No full textInternational audienceMeasurement of serum neurofilament light chain (sNfL) protein is becoming a key biomarker for many neurological diseases. Several immunoassays have been developed to meet these clinical needs, revealing significant differences in terms of variability and results. Here, we propose a French multicenter comparison of 5 sNfL assays
Subcutaneous defibrillator therapy in women
No full textInternational audienceIntroduction While the subcutaneous implantable cardioverter defibrillator (S-ICD) is now an established strategy to prevent sudden cardiac death, the specificities and outcomes associated with the use of this device in women have never been assessed so far.Objective The present study aimed to provide contemporary real-world data on S-ICD use and outcomes in women.Method We used data from the HONEST cohort, a nationwide study including all patients implanted with a S-ICD between 2012 and 2019 in France. Sex-specific outcomes were acceded using a weighting propensity score analysis.Results A total of 1148 women (47.3 ± 15.6 years), accounting for 23.3% of the whole cohort (n = 4924), were enrolled. Indication of implantation was primary prevention in 57.6% (vs. 65.1% in men) and secondary prevention in 42.4% (vs. 34.9% in men; P < 0.009). Coronary artery disease was the most frequent underlying heart disease (38.9% vs. 56.5% in men) and electrical heart disorders were more common in women (26.4% vs. 20.5%; P < 0.001). During a mean follow up of 4.22 ± 2.18 years, women did not have a higher risk of overall complications (aHR 0.95; 95%CI 0.89–1.01; P = 0.065), and of surgical reintervention (aHR 0.95, 95%CI 0.89–1.02, P = 0.094) (Fig. 1). Re-intervention due to pacing need occurred similarly in both sexes (2.4% vs. 2.8%; P = 0.434). Conversely, the risk of inappropriate (aHR 0.81; 95% 0.71–0.91; P < 0.001) and appropriate shocks (aHR 0.91; 95%CI 0.82–1.00; P = 0.045) was lower in women. Finally, there was no difference in risk of death between genders (aHR 1.00; 95%CI 0.97–1.02; P = 0.790).Conclusion This nationwide multicenter cohort study of S-ICD patients showed significant sex-related differences in patient characteristics and outcomes, with a lower risk of appropriate and inappropriate shocks in women as compared with men