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Dexamethasone added to induction and post-remission therapy in older patients with newly diagnosed acute myeloid leukemia
No full textInternational audienceNo abstract availabl
Conversion during Minimally Invasive Left Pancreatectomy: a nationwide study of causes and consequences
No full textInternational audienceObjectives: To identify risk factors for conversion, develop a predictive Conversion Risk Score (CRS), and assess the association between conversion and severe postoperative complications. Background: Conversion occurs in 15-30% of minimally invasive left pancreatectomies (MILP). Risk factors and potential negative impacts on postoperative outcomes are poorly described. Methods: Retrospective, nationwide, multicenter study including all MILP (laparoscopy and robot) performed between 2010 and 2021. Risk factors for conversion were identified by multivariate mixed model, and a CRS was developed on a “training-set” and validated (calibration diagrams and ROC curves) on a “validation-set.” The association between severe complications and conversion was assessed using a propensity score based on the main risk factors for severe complications: age, sex, BMI, ASA score, tumor malignancy, multi-organ resection, operative duration, blood loss, splenectomy. Results: 2104 patients included from 55 centers. Conversion occurred in 15.6% of MILP. Its risk factors were male sex (OR=1.67; P =0.048), BMI≥25 kg/m 2 (OR=2.15; P =0.004), history of laparotomy (OR=2.9; P <0.001), initial pancreatitis (OR=3.58; P =0.007), tumor size≥40 mm (OR=2.12; P =0.003), planned splenectomy (OR=2.63; P <0.001), unplanned splenectomy (OR=4.05; P =0.028), portal vein resection (OR=36.3; P =0.002), multi-organ resection (OR=12.97; P <0.001). A predictive CRS was created based only on preoperatively available variables (the first six), with scores ranging from 0 to 7, corresponding to a conversion risk of 2% to 100%. No association was observed with tumor malignancy, robotic approach, or pancreatectomy volume. Conversion was significantly associated with severe complications [OR=1.80(1.16-2.54)], independent of other risk factors for complications. Conclusions: Conversion during MILP can be predicted by CRS, aiding surgeons in decision-making, given its significant association with severe complications
Association between shortened maternal and fetal telomere length and abnormal fetal development
No full textInternational audienceA number of intrinsic, maternal and environmental factors have been linked to the risk of fetal developmental anomalies. In a previous study, we showed that telomere length (TL) was notably reduced in amniotic fluid when the fetus exhibited a developmental anomaly. In this new study, we measured the fetal and maternal TL for 75 evolutive pregnancies with congenital malformation. We also measured the TL of 50 pregnant women without fetal anomalies and 50 non-pregnant control women who had at least one child with normal development. In fetal samples, telomeres were significantly shortened in cases with congenital anomalies compared to controls (n = 93) (P < 0.0001). Interestingly, age-adjusted maternal TL was also significantly reduced in these cases (P < 0.01). Receiver operating characteristic (ROC) analysis showed that maternal TL, at the optimal cut-off value, identified cases of congenital anomalies with 92% specificity and 73% sensitivity. In addition, fetal and maternal TL were correlated, with 15% to 38% of the variance in fetal TL attributable to maternal TL. Telomere shortening can lead to increased sensitivity to various maternal exposure factors and may contribute to compromised organogenesis, possibly due to inadequate cell proliferation or genomic instability. Measuring maternal TL during the periconceptional period could serve as a useful predictive biomarker for assessing the risk of fetal developmental anomalies
Efficacy and safety of capsaicin 8% patches: The experience of a rheumatology department
No full textInternational audienceBackground: Capsaicin 8% patches are recommended for the treatment of localized neuropathic pain, which is a frequent reason for rheumatology consultations. Objectives: This study aimed to evaluate the efficacy and safety of capsaicin 8% used in our Rheumatology Department. Design: Single-center retrospective study. Methods: Patients treated by capsaicin 8% between October 03, 2019 and December 31, 2023 were included. Their age, sex, pain duration, DN4 score, pain intensity, and the cause of the neuropathic pain were collected. Patch safety was assessed on the day of application and after 15 days. The patient was asked about improvement, pain intensity, and the occurrence of burning sensations. Results: One hundred twelve patients (mean age 62, 70% female) were included. The causes of neuropathic pain were especially scar ( n = 31), digital osteoarthritis ( n = 26), or radiculalgia ( n = 22). Sixty patients reported improvement (54%) at day 15, with a mean percentage of improvement of 59%. Mean pain intensity decreased from 6.4 ± 1.9 to 4.5 ± 2.7 ( p < 0.001). This improvement in pain was significant regardless of etiology. There was no difference in age, sex, and pain duration between improved and unimproved patients. Fifty-eight patients (58/106: 54.7%) experienced burning sensations after patching, mainly of moderate to high intensity (32/52: 61.5%), with an average duration of 2 days. Of the eight unimproved after the first patch, six reported a 50% improvement after the second patch. Conclusion: Capsaicin 8% appeared to be an effective treatment in localized neuropathic pain, whatever the cause. It seemed beneficial to repeat the application after the 1st one had failed. Burning sensations after placement were fairly frequent, usually moderate to high, but lasting only a short time
Ivosidenib in refractory or relapsed IDH1-mutated Acute Myeloid Leukemia patients in real life settings: The ivoobs observational study from the french AML intergroup ALFA/filo
No full textInternational audienceBackground IDH1 R132 mutations are found in about 5-10% of AML at diagnosis. Ivosidenib (IVO) is an oral, targeted, small-molecule inhibitor of the mIDH1 enzyme, approved for IDH1mut newly diagnosed AML aged ≥75 years or who are ineligible for intensive induction chemotherapy. In relapse/refractory settings (R/R), IVO monotherapy yielded promising complete remission or complete remission with partial hematologic recovery (CR/CRi) rate of 30.4% associated with a median overall survival (OS) of 8.8 months (Di Nardo, NEJM, 2018). However, there are very few data regarding IVO use outside clinical trials. In this study, we aimed to evaluate the efficacy and safety of IVO in R/R AML patients in real life settings. Method IVOOBS (NCT06377579) is a retrospective, non-interventional, multicentric study including patients from 32 French centers with newly diagnosed or R/R IDH1mut AML treated with IVO through a compassionate use program. Here, we focused on R/R patients treated with IVO, either as monotherapy or in combination with other therapies between January 2017 and February 2024. The primary objective was OS. Secondary objectives were response rate (ELN2022 criteria), and toxicity. Overall response (ORR) was defined as patients reaching CR, CRi, or CRh at any time. Results Overall, 127 patients were included. Secondary AML were observed in 15.8% (post-MDS/MPN=16, t-AML=4). Median number of previous lines prior IVO onset were 1 [IQR:1-3]; 82 patients (67%) received intensive chemotherapy as first line,36 (29% ) were pre-exposed to VEN prior IVO initiation, while 20 (15.8%) patients received IVO as post hematopoietic stem cell transplantation (HSCT) salvage treatment. 93 patients received IVO monotherapy, 26 in combination with azacitidine (AZA) and 8 with venetoclax (VEN) +/- AZA (defined as AZA/IVO (+/-VEN) group) Most frequent co-mutations were NPM1 (32%), RUNX1 (23%), ASXL1 (21%) and BCOR (18%). Clinicians reported differentiation syndrome (DS) of any grade in of 12 patients (9.5%) (8 with IVO and 4 with IVO+AZA (+/-VEN)). QTc prolongation and febrile neutropenia was observed in 8 (7%) and 15 (12%) patients respectively. Regarding grade 3-4 hematological adverse events (AE), neutropenia, thrombocytopenia and anemia occurred in 4%, 14% and 18% respectively. There were 2 grade 5 AE related to IVO (1 pneumocystis carinii pneumonia and 1 DS) both in IVO monotherapy treated patients. ORR (CR/CRi/CRh) rates was 45.9% (35.8%/9.2%/0.9%), with 46.6% showing no response and 4.6% MLFS (6 patients died prior evaluation). Median time to best response was 2.8 months. Median time on IVO treatment was 6.2 months. ORRs were 39%, 48.6% (p=0.55) with a median time to achieve ORR of 3 months, and 2.8 months in IVO and IVO/AZA (+/-VEN) treated patients, respectively. 65% (68/102) and 75% (55/73) of patients were transfusion independent at 3 and 6 months after IVO initiation, respectively. Prior VEN exposition did not significantly influence ORR probability: (36.1% (13/36) in VEN pre-exposed vs 44.4% (40/90) in VEN naïve (p=0.39). Co-mutations at AML diagnosis did not influence ORR probability including MAPK/RTK mutations. In multivariate analysis for ORR, only higher platelets at IVO onset (HR=1.05, p=0.01) and HU use (HR=0.13, p=.002) were independently associated with ORR. In the 22 patients who received HU to manage initial leukocytosis, ORR rate was 13.6% compared to 53.5% for those without HU requirement (p<0.001). In responding patients, 22.8% (13/57) were bridged to HSCT after a median time of 4.2 months. Only 2 patients relapsed post-transplant. After a median follow-up of 13.9 months, median OS (mOS) of the entire cohort was 14 months. mOS with IVO monotherapy and AZA/IVO (+/-VEN) was 13.2 and 20.2 months, respectively (p=0.16). VEN exposure pre-IVO did not significantly influence OS compared to VEN-naïve patients (HR=0.90, p=0.69). In multivariate analysis, only higher platelets (HR=0.96, p=0.015) and HU use (HR=2.95, p<.001) were independently associated with OS. Conclusion In this real-life study, IVO compares favourably with previously reported prospective studies in R/R settings, with a manageable safety profile. HU use for proliferative disease at IVO onset is associated with a lower response rate and inferior outcome
Diagnostic laparoscopy and cytoreduction surgery in ovarian cancer FIGO III–IV: The impact on survival of one-stage versus two-stage sequence
No full textInternational audienceObjectives: This is a retrospective study designed to assess the impact of two-stage versus single-stage surgical management on survival in patients with FIGO III-IV ovarian neoplasia receiving surgical management.Methods: This is a retrospective, multicenter study, based on the FRANCOGYN group database. Two groups were studied, the first having primary surgical management in a single operation, and the second having two-stage sequence primary surgical management.Results: 208 patients were included in the study. In terms of overall survival, in univariate analysis, there was a statistically significant difference in favor of single-stage surgical management, but this was not demonstrated in multivariate analysis (p = 0,228). Similarly, in terms of recurrence-free survival, there was no statistically significant difference between the two groups studied (p = 0,123).Conclusion: Performing exploratory laparoscopy at the same time as cytoreduction surgery does not significantly improve recurrence-free survival in patients with FIGO III-IV ovarian cancer. This trend was also observed in the overall survival analysis
Pure Red Cell Aplasia Associated With Thymic Tumors, a Nationwide Retrospective Study
No full textInternational audiencePure red cell aplasia (PRCA) is the most frequent autoimmune cytopenia associated with thymic tumors (TTs). In a nationwide retrospective study, we included 41 patients (22 women, median age 62 years). At PRCA diagnosis, the mean hemoglobin level was 6.6 ± 2.1 g/dL, and the reticulocyte count was 6 ± 5 × 10 9 /L. PRCA was diagnosed before TT (8%, median delay 52 months), simultaneously (46%) or after TT (46%, median delay 34 months). Fourteen patients (34%) had definite Good syndrome. Thymectomy without immunosuppressive treatment provided a single sustainable PRCA response. Twenty‐two patients (54%) experienced multiple PRCA relapses (Median 2). When PRCA was present at TT diagnosis, the risk of PRCA relapse was higher ( p < 0.01), while TT staging, TT relapse, and Good syndrome were not associated with PRCA relapses. Corticosteroids led to a 77% initial response rate with frequent relapses during taper or at discontinuation. Cyclosporine A provided a 71% response rate. Overall response rates and time to response were similar with corticosteroids and cyclosporine A. Sirolimus led to a 50% response rate in refractory cases. Severe infectious events requiring hospitalizations were frequent (44%). After a mean follow‐up of 50 months, five patients (12%) died, three of whom died from TT relapse. Good syndrome was not significantly associated with an increased risk of infection, PRCA relapse, or death. Our findings highlight the severe phenotype of the association of TT and PRCA. While most patients achieve PRCA response under immunosuppressive therapy, high infection incidence and thymoma relapse are responsible for severe morbidity
Teaching Palliative Medicine in the Medical School Clerkship in France. A National E-Survey
No full textInternational audienceContext: There is considerable variation in the way that palliative medicine is taught allaround the globe. No comprehensive study has yet been conducted on the content of this teaching, particularly regarding clerkships and theoretical teaching (lectures, group teaching) in France. This would facilitate the standardisation of palliative care training throughout the country.Objectives: The main objective of this study is to provide a comprehensive description of the theoretical and practical training in palliative medicine that is offered during medical school clinical yearsstudies in France.Methods: We conducted an online specially designed survey of the 34 medical schools in France, that offer a complete second cycle of medical studies. It was sent to the head of teaching between February and April 2024.Results: The response rate was 100%. In terms of clerkships, 30 institutions (88.24%) offer placements to second-cycle students (primarily in teaching hospitals) but for a limited number of their students. Thirty-three universities provided theoretical teaching, which is predominantly lecture-based (58.82%) or group-based (large group 38.24% and small group 47.06%). Moreover, we frequently observed a combination of different teaching methods, in particular group teaching and lectures (27%).Conclusion: Training in palliative medicine during medical school in France varies widely. Practical training is available but limited in access, while theoretical training meets international standards but does not fully align with the EAPC objectives. Based on these results, the authors advocates for developing an access for all students to clerkships, and the development of theoretical teaching preferably in small groups in all universities
Scientific opinion of the French Agency for Food, Environmental and Occupational Health and Safety on updating the state of the evidence on the prevention of neural tube defects through vitamin B9 intake
No full textANSES: Request No 2023-SA-0019International audienceFollowing a request from the French Directorate General for Health, ANSES was asked to deliver a scientific opinion on the state of the evidence on the prevention of neural tube defects (NTDs) by increasing vitamin B9 intake. The opinion estimates the prevalence of NTDs in France using data collected between 2012 and 2021 from five French registries reporting a mean prevalence of 13.5 per 10 000 births. The efficacy of vitamin B9 supplementation and food fortification was evaluated by conducting systematic reviews of human studies. The opinion also provides a comparative analysis of international vitamin B9 fortification strategies, followed by simulations to assess fortification levels and their potential to reduce inadequate vitamin B9 intake in France. The Expert Committee and ANSES concluded that fortifying flour (both refined and whole grain) with 200 μg of folic acid per 100 g would enable 90% of women to meet the Dietary Reference Value for adults and ensure a mean intake exceeding the adequate intake of 600 μg/day of dietary folate equivalents during pregnancy. However, this measure would not replace the recommendation for women to take a folic acid supplement (400 μg/day) from the moment they try to conceive until 12 weeks of pregnancy. ANSES further recommended initiating a public consultation of all the stakeholders
SLC10A7 regulates O-GalNAc glycosylation and Ca2+ homeostasis in the secretory pathway: insights into SLC10A7-CDG
No full textInternational audienceAbstract Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented. The emergence of CDG resulting from defects in ER/ Golgi homeostasis makes this even more difficult. SLC10A7 belongs to the SLC10 protein family, known as bile acid and steroid transport family, exhibiting a unique structure. It shows a ubiquitous expression and is linked to negative calcium regulation in cells. The mechanisms by which SLC10A7 deficiency leads to Golgi glycosylation abnormalities are unknown. The present study identifies major O -glycosylation defects in both SLC10A7 KO HAP1 cells and SLC10A7-CDG patient fibroblasts and reveals an increased ER and Golgi calcium contents. We also show that the abundance of COSMC and C1GALT1 is altered in SLC10A7-CDG patient cells, as well as the subcellular Golgi localization of the Ca 2+ -binding Cab45 protein. Finally, we demonstrate that supraphysiological manganese supplementation suppresses the deficient electrophoretic mobility of TGN46 by an aberrant transfer of GalNAc residues, and reveal COSMC Mn 2+ sensitivity. These findings provide novel insights into the mechanisms of Golgi glycosylation defects in SLC10A7-deficient cells. They show that SLC10A7 is a key Golgi transmembrane protein maintaining the tight regulation of Ca 2+ homeostasis in the ER and Golgi compartments, both essential for glycosylation