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Methodological concerns and clinical relevance: a critical appraisal of the meta-analysis on biosimilars versus originator follitropin alfa in ART
No full textInternational audienceNo abstract availabl
EST-IL PERTINENT DE MOBILISER DES PATIENTS FORMATEURS DANS DES ECOS ?
No full textAs part of the reform of the second cycle of medical studies, a collaborative creation process was developed and implemented. This creation was initiated with patient partners and medical students supervised by a teaching team working in partnership: teaching physicians, patient partner trainers/assessors and patient trainers as part of additional training on the theme of the Art of Care in partnership with the patient. The main idea is for students and patient partners to consult with each other at each ECOS station, followed by a systematic debriefing session and, therefore, formative ECOS. This initiative has been institutionalised since 2022 in a medical faculty as a compulsory formative examination at the end of a general medicine internship. It allows for a rethinking of the place of these ECOS in the learning process offered to second-cycle medical students by integrating a progression specific to pedagogical processes in the competency-based approach. Both students and supervisors, doctors and patients alike, see the benefits of this, which invites reflection on possible adjustments to this reform of postgraduate studies for learning that is more in tune with current changes in healthcare. This is what this article aims to shed light onDans le cadre de la réforme de 2ème cycle des études de médecine, un processus de création en partenariat a été réalisé et mis en œuvre. Cette création a été initiée avec des patients partenaires et des étudiants en médecine encadrés par une équipe pédagogique en partenariat : médecins enseignants, patients partenaires formateurs évaluateurs et de patients formateurs dans le cadre d’une formation complémentaire sur le thème de l’Art du Soin en partenariat avec le patient. L’idée maitresse consiste en la consultation entre étudiants et patients partenaires au sein de chaque station ECOS avec un temps de debriefing systématique en conclusion et donc d’ECOS formatifs. Cette initiative est institutionnalisée depuis 2022 dans une faculté de médecine comme examen obligatoire formatif de fin de stage de médecine générale. Elle permet de repenser la place de ces ECOS au cours du processus d’apprentissage proposé aux étudiants en médecine de 2ème cycle en y intégrant une progressivité propre aux processus pédagogiques dans l’approche par compétences. Tant les étudiants que les encadrants, médecins comme patients, y perçoivent les bénéfices, ce qui invite à réfléchir à de possibles ajustements dans cette réforme des études de second cycle pour un apprentissage plus en phase avec les mutations actuelles dans le soin. C’est ce que propose d’éclairer cet article
Whole Exome Sequencing of Adult Patients With Evans Syndrome Reveals Pathogenic Variants Associated With Autoimmunity
No full textInternational audienceNo abstract
In‐hospital and 1 year incremental prognostic value of drug abuse detection in acute heart failure
No full textInternational audienceAims The study aims to assess the in‐hospital and 1 year incremental prognostic value of recent drug abuse use, detected by a systematic urinary screening, in a consecutive cohort of patients hospitalized for acute heart failure (AHF). Methods All patients admitted for AHF with a drug abuse screening using a urinary assay were included in this prospective multicentric study (39 French centres). The outcomes were (i) in‐hospital major adverse cardiovascular events (MACEs) defined as all‐cause death, resuscitated cardiac arrest or cardiogenic shock; and (ii) 1 year MACEs defined as cardiovascular death or hospitalization for AHF. Incremental prognostic value was assessed using the C‐index, the global χ 2 and likelihood‐ratio (LR) test, the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results In total, 458 patients with AHF were included (mean age 68 ± 14 years, 67% male, 79% of new heart failure onset). In‐hospital and 1 year MACEs occurred, respectively, in 65 (14.2%) and 129 (28.2%) patients. Drug abuse detection was independently associated with in‐hospital MACEs [model 1—known comorbidities: odds ratio (OR) = 4.46, 95% confidence interval (CI) (1.88–10.3), P < 0.001; model 2—clinical severity: OR = 3.64, 95% CI (1.56–8.26), P = 0.002], even after propensity‐matched population analysis [OR = 3.34, 95% CI (1.32–8.70), P = 0.011], with a significant incremental prognostic value over and above traditional risk factors ( C ‐statistic improvement 0.04 with LR test P < 0.001 for both models). Patients with drug abuse detection had worse 1 year survival: HR = 1.82, 95% CI (1.13–2.92), P = 0.012. Drug abuse detection was independently associated with 1 year MACEs after adjustment with traditional prognosticators [OR = 2.54, 95% CI (1.28–4.98), P = 0.008] and propensity‐matched population analysis [OR = 2.77, 95% CI (1.98–5.21), P = 0.001], with an incremental prognostic value as well ( C ‐statistic improvement 0.02, LR test P < 0.001, positive NRI and IDI). Conclusions Drug abuse use was independently associated with a higher occurrence of both in‐hospital and 1 year MACEs with an incremental prognostic value. These results suggest a potential interest of a systematic illicit drug screening in these patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05063097
Mitochondrial targets in ischaemic heart disease and heart failure, and their potential for a more efficient clinical translation. A scientific statement of the ESC Working Group on Cellular Biology of the Heart and the ESC Working Group on Myocardial Function
No full textInternational audienceAcute myocardial infarction (MI) remains a major cause of death and disability worldwide. No adjuvant treatment has yet been fully validated in patients to limit the progression from the initial tissue damage due to acute MI, to the development of heart failure. However, mitochondria have long been demonstrated to be a key target for cardioprotective strategies to reduce cell death that leads to left ventricular dysfunction and ultimately heart failure. While pre‐clinical studies have investigated several mitoprotective strategies targeting different mitochondrial functions, such as oxidative stress or permeability transition pore opening, none have shown successful clinical translation so far. In this European Society of Cardiology scientific statement, we present recent research advances in the understanding of the mitochondrial alterations occurring in MI and in the discovery of key components of mitochondrial structure and function in order to improve drug development. We discuss the reasons for the failure of clinical translation and the remaining obstacles that need to be addressed, including timing of drug administration, tissue bioavailability and efficient mitochondrial targeting, together with the mitochondrial impact derived from risk factors, comorbidities and comedications. Taken together, this scientific statement aims to provides a consensus opinion from clinicians and basic scientists to translate some of the most promising mitoprotective targets into the clinical setting to protect against MI and heart failure
Beneficial Effects of Omega-3 Fatty Acids on Obesity and Related Metabolic and Chronic Inflammatory Diseases
No full textInternational audienceOmega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials
Temporary Transvenous Pacing Performed in the Intensive Care Unit or in the Catheterization Laboratory
No full textInternational audienceABSTRACT Background Temporary transvenous pacing (TTP) is a common procedure, predominantly performed in the catheterization laboratory (cath lab) because of presumed lower complication rate. This study aims to evaluate the efficacy and safety of TTP placement in the ICU compared to TTP placement in the cath lab. Methods This retrospective, real‐life study included all patients requiring TTP in a tertiary care ICU between 2019 and 2022. Patients’ characteristics, TTP‐related data, outcomes, and complications were compared between groups (ICU vs. cath lab). Results Data from 193 patients receiving TTP were analyzed; 68.4% received TTP in the ICU and 31.6% in the cath lab. The main indication was atrioventricular block in 154 patients (79.8%). The operator was less frequently an interventional cardiologist in the ICU (12.1%) compared to the cath lab (100%, p < 0.001). TTP in the ICU was more frequently performed using a jugular access (72.0% vs. 1.6%), a right‐sided laterality (88.7% vs. 43.6%), and a balloon‐tipped catheter (100% vs. 0%, p < 0.001 for all comparisons). Success was 100% in both groups. The overall complication rate was 16.6%, with no significant difference between both groups (14.4% ICU vs. 21.3% cath lab, p = 0.13), but a tendency toward higher complications in the cath lab group (especially tamponade, lead displacement, and CIED infection). Conclusion In a daily clinical scenario, TTP placement appears as safe in the ICU than in the cath lab, regardless of the operator's level of expertise when performed in accordance with best practices. Nevertheless, TTP complications remain high, and alternatives should be used whenever possible
A multivariable prediction model for invasive pulmonary aspergillosis in immunocompromised patients with acute respiratory failure (IPA-GRRR-OH score)
No full textInternational audiencePurpose: Invasive pulmonary aspergillosis (IPA) is a life-threatening opportunistic infection in immunocompromised patients. The diagnosis is often made late, with mortality reaching 90% when mechanical ventilation is needed. We sought to develop and validate a risk prediction model for the diagnosis of IPA.Methods: We used two independent datasets of immunocompromised patients with acute respiratory failure admitted to 12 intensive care units (ICUs). The derivation dataset include 3262 patients. Factors associated with probable or proven IPA were identified, and a risk prediction model was developed. This model was then validated in a prospective dataset (776 patients).Results: IPA prevalence was 4.5% (146/3262) and 3.3% (26/776), in the derivation and the validation cohorts, respectively. The final model included eight variables constitutive of the IPA-GRRR-OH score: type of immunosuppression, high-dose or long-term corticosteroids, neutropenia, the presence of structural lung disease, time from symptoms onset to ICU admission > 7 days, hemoptysis, focal alveolar pattern on the chest imaging, and viral co-infection. The median score [IQR] was 2 [1-3] in the derivation and 1 [0-3] in the validation cohort. The best cutoff score for IPA diagnosis was 4 (sensitivity 23.1%; specificity 90.5%; negative predictive value 91.4%). Discrimination and calibration were good in both the derivation (AUC 0.72 [0.68-0.76]) and the validation cohort (AUC 0.85 [0.76-0.93]).Conclusion: The IPA-GRRR-OH is a clinical score, easily available at ICU admission, which reliably predicts IPA in immunocompromised patients with acute respiratory failure. Studies to demonstrate benefits from the bedside implementation of this score are warranted
Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort
No full textInternational audienceBackground: Hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) can be caused by SMAD4 pathogenic variants. SMAD4 is a common transcription factor of the BMP/TGFβ signalling pathway. In this study, we developed a cell-based functional assay to address the pathogenicity of SMAD4 variants identified in the French HHT cohort.Methods: SMAD4 variants were generated by site-directed mutagenesis. A functional assay was developed in a cell line that does not express SMAD4, and the different SMAD4 variants were tested for their capacity to activate the BMP and TGFβ response using luciferase reporter assays.Results: Twelve SMAD4 variants were identified and studied. We were able to develop a robust functional assay for these variants. All the expressed variants resulted in loss of function (LOF) in response to BMP9 or TGFβ1 stimulation. SMAD4 variants within the MH2 domain expressed SMAD4 mutated proteins that were unable to hetero-oligomerise with other SMADs, which could explain their LOF. Finally, we tested primary human endothelial cells isolated from patients with HHT carrying SMAD4 heterozygous pathogenic variants and observed that they behaved like the control cells at rest or when stimulated with BMP9.Conclusion: We developed a SMAD4 functional assay that allows discrimination between benign and pathogenic SMAD4 variants. We demonstrated that the underlying molecular mechanism of this pathogenicity is due mostly to a loss of hetero-oligomerisation. This assay will be transferable to clinical genetic laboratories and will improve the diagnosis of patients with HHT–JPS
sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial
No full textInternational audienceWe investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15-0.38], p < 10-9; nucleosomes: aHR 0.62, 95% CI [0.48-0.81], p < 10-3). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65-6.28], p < 10-5). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target