Portail HAL de l'Université Picardie Jules Verne
Not a member yet
32425 research outputs found
Sort by
Therapy-related core binding factor Acute Myeloid Leukemia – a Study of the french acute leukemia intergroup
No full textInternational audienceIntroduction Therapy-related CBF-AMLs represent approximately 10% of all CBF-AMLs and are associated with poorer outcomes, partly due to the associated solid tumor. Existing studies are small, and more data—especially NGS and cytogenetics—are needed to better define their characteristics and prognosis. Methods We analyzed data from a retrospective multicenter study (NCT05070208) and the prospective CBF-2006 trial (NCT00428558, Jourdan et al. 2014) from the French AML intergroup, including CBF-AML patients diagnosed between 2007–2020. Cases with prior chemo- or radiotherapy were classified as therapy-related (t-AML). Baseline characteristics were compared in the overall cohort. Outcomes were assessed in a sub-population of fit patients (≤80 years, cancer in remission, intensive chemotherapy). Centralized NGS was performed using 40- and 68-gene panels (36 genes in common), and MRD was assessed by RT-qPCR for RUNX1::RUNX1T1 and CBFB::MYH11. Results Among 749 CBF-AML patients included between 2007 and 2021, 78 had t-AML. t-AML patients were older (median age: 59 vs. 45 years, p<0.001), more likely to be female (68% vs. 44%, p<0.001), and had lower white blood cell counts (WBC) at diagnosis (median: 6 vs. 15 G/L, p<0.001). was the most common prior neoplasm (42%). Median interval from chemo/radiotherapy to t-AML onset was 38 months (IQR [interquartile range]: 25–69). Neoplasms were in complete remission after chemotherapy (74%) and/or radiotherapy (49%) at CBF-AML diagnosis in 83% pts and remained in sustained remission in 78% after a median follow up of 1.8 years. The distribution of RUNX1::RUNX1T1 and CBFB::MYH11 subtypes was similar between therapy-related and de novo cases (44% and 43% for RUNX1::RUNX1T1, p>0.9). Cytogenetically, X chromosome deletions were more frequent in t-AML (16% vs. 8%, p=0.016). t-AMLs showed fewer on NGS (63% vs. 75%, p = 0.019), and fewer FLT3 mutations (10% vs. 24%, p = 0.03). No other difference was observed in the mutational landscape of t-AML, including KIT and TP53 alterations. In the selected population of patients without active cancer at AML diagnosis and treated with intensive chemotherapy (n=693, including 57 t-AML), induction regimens were mainly based on 7+3 ( in t-AML vs 72% in non-t-AML, p=0.07) and consolidation courses on intermediate/high dose cytarabine courses (93% in t-AML vs 90% in non-t-AML, p=0.64). Gemtuzumab-ozogamycin was added to Cx in 9% of t-AML (vs. 10% of non-t-AML, p=1.0). Allogeneic transplant in first complete remission was performed in 9% of t-AML and 5% of non-t-AML (p=0.21). Therapy-related AML patients had a CR/CRp rate of 95%, not different from de novo patients (95%, p=0.74). MRD after one cycle of induction was not different in t-AML in bone marrow (median: 0.20% [IQR: 0.04-0.82%] vs. 0.17% [IQR: 0.03-0.49%], p=0.50) nor in peripheral blood (median: 0.02% [IQR: 0.002-0.14%] vs. 0.03% [IQR: 0.001-0.19%], p=0.85). With a median follow-up of 5.3 years (IQR :3.9-6.8), the 3-year cumulative incidence (CI) of relapse was 41% (95%CI [confidence interval]:27%-54%) in t-AML patients and 38% (95%CI:34%-42%) in non-t-AML patients (csHR=1.07 [95%CI:0.69-1.68], p=0.76). No difference was also observed for non-relapse mortality (NRM) (3-year CI-NRM: 2% [95%CI:0%-9%] for t-AML vs. 3% [95%CI:2%-5%] for non-t-AML, csHR=0.87 [95%CI:0.21-3.66], p=0.85). Overall survival (OS) was lower in t-AML in univariable analysis (3-year OS: 62% [95%CI:50%-77%] in t-AML vs 79% [95%CI:75%-82%] in non-t-AML, p=0.03). Nevertheless, this was not confirmed in multivariable analysis (HR=1.36, 95%CI:0.84-2.18, p=0.21 for t-AML) when accounting for age (per 10 years of age HR=1.27, 95%CI:1.14-1.42, p<0.001), WBC count (log10 scale HR=1.25, 95%CI:0.94-1.65, p=0.12), and CBF subtype (HR=1.19, 95%CI:0.87-1.62, p=0.29 for RUNX1::RUNX1T1). In patients who experienced relapse (n=249 including 21 t-AML), OS after relapse was dismal in t-AML (16% [95%CI:6%-45%] vs 56% [95%CI:50%-64%], p<0.0001). Conclusion This study shows that therapy-related CBF-AML patients are older, have lower WBC at diagnosis, and present with similar molecular profiles compared to de novo cases. Among a homogenous cohort of patients without active cancer and treated with intensive chemotherapy, there were no differences in CR/CRp rates, relapse incidence, or non-relapse mortality. Unlike previous studies, overall survival was not significantly different after multivariable adjustment for age, WBC count, and CBF subtype
Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis
No full textInternational audienceBackground: Janus Kinase (JAK) inhibitors are the current standard of care for patients (pts) with myelofibrosis (MF). However, many pts may not achieve spleen volume reduction (SVR) or total symptom score (TSS) response after frontline treatment, and most pts with relapsed/refractory (R/R) MF lack adequate responses. Momelotinib (MMB), a recently approved JAK/ACVR1 inhibitor for MF pts with anemia, showed symptom and spleen responses in about 25% pts in R/R setting. Combination strategies of JAK inhibitor and agent with unique mechanism of action and minimal overlapping toxicities (e.g. cytopenias) are needed to improve response rates in MF. PIM1 expression is upregulated in MF CD34 cells. In preclinical models, PIM1 knockout (KO) was shown to prevent MF progression without affecting PLT counts, whereas pan-PIM KO caused thrombocytopenia (TCP). Nuvisertib (NUVI, TP-3654), an oral investigational highly selective PIM1 kinase inhibitor, alone and in combination with ruxolitinib (RUX) showed spleen size reduction and bone marrow (BM) fibrosis improvement in JAK2V617F and MPLW515L MF mouse models. Preliminary data from the ongoing Phase 1/2 study in R/R MF pts with PLT count ≥25 x 109/L showed that NUVI monotherapy was well tolerated with limited myelosuppression, and clinical activity including SVR and TSS responses strongly correlating with cytokines modulation, and hemoglobin (Hgb), PLT, and BM improvement. Preclinical and monotherapy clinical data support the development of NUVI + MMB combo in MF. Methods: The global Phase 1/2 study evaluates the safety and efficacy of NUVI + MMB combo in pts with MF (NCT04176198, Arm 3). Key eligibility criteria include primary or secondary MF, previously treated with JAK inhibitor, DIPSS intermediate or high-risk MF, Hgb <10 g/dL, PLT ≥50 x 109/L, splenomegaly (≥450 cm3 by imaging), and ≥2 measurable symptoms with each score ≥3 or a total average score of ≥10 per MFSAF v4. The study aims to identify the RP2D of NUVI when given with MMB, and to assess the safety, clinical activity (SVR, TSS improvement), and PK and PD markers (cytokine, BM fibrosis etc.). Results: Here we present the first ever combination data of MMB in MF. As of 29 May 2025, total 18 pts enrolled in 4 dose levels of NUVI BID at 240 mg (n=4), 360 mg (n=8), 480 mg (n=5) and 720 mg (N=1) + MMB 200 mg QD using the BLRM dose escalation. At baseline, median age 75 years (range 51, 82); TSS 29 (9, 37); spleen volume 1370 cm3 (614, 4250); Hgb 9.1 g/dL (7.9, 10.1; 50% pts required transfusion); and PLT 196 x 109/L (81, 601). All pts received prior JAK inhibitor, and 53% pts had high molecular risk mutation. Median treatment duration of NUVI + MMB combo was 21 weeks (1, 30), and 13 of 18 (72%) pts were on treatment. One DLT of Grade 4 TCP without any bleeding occurred in NUVI 360 mg BID + MMB 200 mg QD dose. Treatment-related adverse events (TRAEs) occurring in ≥20% of pts were diarrhea, nausea, and TCP. Grade ≥3 TRAE occurring in ≥2 pts included TCP (n=2; 1 pt had baseline TCP). Mean Hgb and PLT remained stable throughout the 24-week treatment. Emerging NUVI + MMB combo safety data was generally consistent with NUVI monotherapy data. 5 pts in the NUVI 360 mg BID + MMB 200 mg QD dose completed ≥24 weeks of treatment and were considered efficacy evaluable. TSS improvement at WK24 was observed in all 5 patients (median change -65%, range -38% to -72%); 3 of 5 (60%) pts showed ≥50% TSS reduction. In addition, absolute reduction was observed in all 7 symptom parameters, including >50% reduction in mean fatigue score at WK24. 2 of 5 (40%) pts showed ≥25% SVR at WK24. Decreased EN-RAGE and increased adiponectin were observed in all 5 pts, consistent with NUVI monotherapy findings where modulation of these cytokines strongly correlated with TSS50, individual symptoms and SVR25 responses. Anemia improvement was observed in 2 of 5 (40%) pts during 24 weeks of treatment: 1 pt showed Hgb response (defined as mean ≥1.0 g/dL increase for ≥12 weeks without transfusion), and 1 pt achieved a >50% reduction in transfusions. Dose escalation is ongoing, and updated data will be presented.Conclusions: NUVI + MMB combo appeared to be well tolerated. Preliminary data showed early clinical activity including 60% TSS50 response and absolute symptom improvement, 40% SVR25 response, cytokine modulation and anemia improvement in R/R MF pts with anemia. Preliminary data supports further development of NUVI + MMB combo for pts with MF
Characteristics of tuberculosis in elderly adults: A multicenter French study
No full textInternational audienceIntroduction: The incidence of tuberculosis (TB) remains high in elderly adults in France. Immunosenescence and comorbidities challenge both diagnosis and treatment in this population. Recent data describing TB characteristics and outcomes in the elderlies are scarce. We aimed to describe clinical and microbiological features of TB in the elderly population and to identify factors associated with 2-year mortality.Patients and methods: We conducted a retrospective multicenter study including patients aged ≥ 75 years who were diagnosed with TB between 2010 and 2020 across 18 centers. A multivariate analysis was used to identify factors independently associated with 2-year mortality.Results: A total of 295 patients were included: mainly born in France (57%). Immunosuppression was rare (9.8%). Fever and cough were uncommon, while weight loss was the most frequent symptom (60.3%), significantly associated with diagnostic delays. Pulmonary TB was the predominant form (63.1%) with higher culture positivity observed in this group and in the oldest patients. Isoniazid resistance was rare (5.2%). Standard quadritherapy was the most common initial regimen and was not associated with higher rates of adverse events. At two-year follow-up, overall mortality was 31.3%. In multivariate analysis, mortality was significantly associated with severe renal failure, living in nursing home or long-term care facilities, and weight loss at presentation.Conclusion: This study highlights the atypical presentation of TB in elderly adults and the continued use of standard quadritherapy despite low drug resistance. Weight loss, though nonspecific, appears to be the most prognostic symptom and is associated with delayed diagnosis and higher mortality
Intestinal Ultrasound Transmural Healing Was Associated With Improved Long‐Term Outcomes Among Patients With Endoscopic Remission: Results of a Prospective Study
No full textInternational audienceBackground STRIDE II guidelines recognise endoscopic healing as a main therapeutic target in Crohn's disease (CD). Nevertheless, transmural healing (TH) could reduce the risk of long‐term complications. Aim To assess the impact of intestinal ultrasound (IUS) TH on CD long‐term among patients with endoscopic healing. Method We conducted a prospective study of consecutive patients with CD who underwent colonoscopy with endoscopic healing (CDEIS < 4) and IUS. IUS TH was defined by a bowel wall thickness < 3 mm without colour Doppler signal. The primary endpoint was CD relapse (drug intensification, initiation of steroid, CD‐related hospitalization or surgery, luminal stricture/fistula or perianal CD). Results We included 93 patients. IUS TH was observed in 73%. No difference in median IBD‐risk score was observed among patients with and without IUS TH (22 (IQR 7–41) vs. 30 (IQR 13–55); p = 0.15). After a median follow‐up of 22.5 months (IQR 19.3–23.7), the cumulative risk of relapse was significantly lower among patients with IUS healing (17% vs. 48%; p = 0.007). The benefit of TH remained when considering only patients with complete endoscopic healing (CDEIS = 0) (12‐month relapse rate, 2% vs. 33%; p = 0.03). The risk of CD‐related hospitalization (3% vs. 16%; p = 0.04) and perianal CD (3% vs. 16%; p = 0.04) were significantly lower among patients with IUS healing. In multivariate analysis, the absence of TH remained the only independent factor associated with CD relapse (hazard ratio 2.6 (1.1–6.2); p = 0.03). Conclusion IUS TH was associated with improved long‐term outcomes with lower risks of CD relapse, hospitalization, and perianal CD
Miscellanées et épistolographie
No full textInternational audienceLes Nouantiquæ Lectiones de Franciscus Modius forment une œuvre hybride, au confluent de deux genres caractéristiques de l’humanisme : les miscellanées et la correspondance. En les contaminant, Modius revivifie en profondeur des pratiques traditionnelles. Il peut ainsi consolider sa place, tant auprès de ses protecteurs qu’au sein de la République des Lettres, tout en militant en faveur d’une approche renouvelée de la littérature latine et de ses méthodes de transmission
Étude de dissection anatomique du retinaculum supérieur des extenseurs de la jambe et application à la clinique du syndrome des loges
No full textInternational audienceIntroductionLe syndrome des loges est une pathologie des membres définie comme une mise en tension excessive et maintenue des contenants de la loge. Les atteintes peuvent être localisées et circonscrites au tiers inférieur de la loge antérieure de la jambe, définissant alors un syndrome des loges partiel. Cette délimitation stricte serait expliquée par la présence du retinaculum supérieur des extenseurs des orteils, prolongement du fascia crural de la jambe.ObjectifsIdentifier et décrire les éléments au sein du retinaculum supérieur des extenseurs.MatérielsL’étude s’appuie sur la dissection d’un échantillon randomisé de 24 jambes embaumées.MéthodesLa face antérolatérale de la jambe était exposée par une rotation interne. La dissection du plan superficiel s’est attachée à préserver le nerf fibulaire superficiel et ses branches. Le retinaculum supérieur des extenseurs des orteils a été mesuré sur sa hauteur. Puis le fascia crural a été ouvert afin de repérer, identifier et caractériser les structures profondes. Les prolongements fasciaux délimitant une coulisse tendineuse propre ont été relevés et notés.RésultatsNous avons retrouvé des fibres musculaires du long extenseur de l’hallux dans 92 % des cas, des fibres musculaires du long extenseur des orteils dans 100 % des cas pour le 5e orteil et des fibres musculaires du tibial antérieur dans 42 %. Un muscle fibulaire antérieur était présent dans 87,5 % des cas, toujours avec des fibres musculaires. Le nerf fibulaire superficiel ou ses branches avaient une direction en bas et en dedans, étaient placés à 2,98 cm du tibia au bord supérieur du retinaculum et à 3,64 cm au moment de sa traversée du fascia.ConclusionPour aider au diagnostic du syndrome des loges, nous pouvons orienter notre exploration clinique sur les altérations des muscles long extenseur des orteils et surtout vers le 5e orteil, long extenseur de l’hallux et troisième fibulaire. Une aponévrotomie peut être réalisée dans les 2 cm en dehors du tibia pour ne pas léser le nerf fibulaire superficiel
Étude radio anatomique du confluent des sinus veineux du crâne en IRM
No full textInternational audienceIntroductionLe confluent des sinus (ou torcular) est classiquement décrit comme la réunion du sinus sagittal supérieur, du sinus droit, et parfois d’un sinus occipital, d’où s’évacue ensuite le flux sanguin par les sinus transverses. Il existe en réalité de nombreuses variations et leur identification est essentielle, notamment en chirurgie de la fosse postérieure afin de réduire les complications post-opératoires liées au sacrifice veineux [1].ObjectifProposer une description anatomique détaillée du confluent des sinus.Matériels et méthodesDes reconstructions tridimensionnelles ont été réalisées à partir de 80 IRM injectées au gadolinium sélectionnées. La configuration du confluent des sinus a été étudiée. Divers paramètres comme le diamètre des sinus transverses et le nombre de veines collatérales ont été observés ou mesurés.RésultatsAu total, 16 formes différentes du confluent des sinus ont été observées. Les trois plus fréquentes étaient : le type 1 qui correspond à la description classique du confluent des sinus (25 %), le type 5 dans lequel le sinus droit se divise pour former les deux sinus transverses et le sinus sagittal supérieur est latéralisé à droite (18,75 %) et le type 2A où le sinus sagittal supérieur est latéralisé à droite et le sinus droit est médian (12,5 %). Le sinus occipital était visible chez 50 % des individus. Une asymétrie entre les deux sinus transverses était principalement retrouvée avec un sinus droit dominant (47,5 %).ConclusionLa diversité morphologique du confluent des sinus met en évidence l’importance d’une étude préopératoire du réseau veineux cérébral pour la chirurgie de la fosse postérieure. Une attention particulière doit être portée aux variations susceptibles d’influencer le flux sanguin cérébral
Clinical characteristics, management and outcomes of enterococcal infective endocarditis: an ancillary study from the ESC-EORP EURO-ENDO registry
No full textInternational audienceBackground Enterococcal infective endocarditis (EIE) represents a growing proportion of infective endocarditis (IE) cases, particularly among elderly and comorbid patients. EIE poses diagnostic and therapeutic challenges, notably regarding optimal antimicrobial therapy and surgical decision-making. We aimed to compare the clinical characteristics, management, and outcomes of EIE versus non-enterococcal IE (NEIE) in the ESC-EORP EURO-ENDO registry. Methods This ancillary analysis of the prospective EURO-ENDO registry included adult patients with definite or possible IE enrolled between January 2016 and March 2018. Patients with monomicrobial EIE were compared with those with NEIE. Clinical, microbiological, imaging, and therapeutic data were analyzed. Multivariable logistic regression including EuroSCORE II and valve status identified independent predictors of in-hospital mortality. Results Among 3 083 patients, 365 (12 %) had monomicrobial EIE. Compared with NEIE, EIE patients were older (mean 68 vs 58 years), had more comorbidities, and more frequent prosthetic valve involvement (41 % vs 26 %). Aortic valve localization and colonic uptake on PET/CT were also more common. In-hospital mortality was similar (16 % vs 17 %). After adjustment for EuroSCORE II and valve status, EIE was not independently associated with higher in-hospital mortality (adjusted OR 0.67 [95 % CI 0.42–1.04]; p = 0.083). Among 195 EIE patients with one-year follow-up, recurrence occurred in 6 %. Healthcare-associated acquisition, prosthetic valve infection, and recurrence were associated with worse outcomes and lower surgical rates. Conclusions EIE affects older, high-risk patients. After adjustment for operative risk, mortality was comparable to other etiologies, highlighting the need for tailored diagnostic and therapeutic strategies
Care pathways for patients with cognitive impairment and chronic kidney disease
No full textInternational audienceVarious epidemiological datasets and pathophysiological hypotheses have highlighted a significant link between chronic kidney disease (CKD) and cognitive impairment (CI); each condition can potentially exacerbate the other. Here, we review the mutual consequences of CKD and CI on health outcomes and care pathways and highlight the complexities due to the involvement of different specialists. Our narrative review covers (i) the burden of CI among patients with CKD, (ii) the impact of CI on kidney health, (iii) access to kidney replacement therapy for people with CI, (iv) resources in cognitive care and (v) potential models for integrated 'nephrocognitive' care. CI (ranging from mild CI to dementia) has a significant impact on older adults, with a high prevalence and a strong association with CKD. Furthermore, CI complicates the management of CKD and leads to a higher mortality rate, poorer quality of life and higher healthcare costs. Due to difficulties in symptom description and poor adherence to medical guidelines, the presence of CI can delay the treatment of CKD. Access to care for patients with both CKD and CI is hindered by physical, cognitive and systemic barriers, resulting in less intensive, less timely care. Multidisciplinary approaches involving nephrologists, geriatricians, neurologists and other specialists are crucial. Integrated care models focused on person-centred approaches, shared decision-making and continuous co-management may improve outcomes. Future research should focus on the putative beneficial effects of these various strategies on both clinical and patient-reported outcomes