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Acute Myeloid Leukaemia following Direct Acting Antiviral drugs in HCV-infected patients: a 10 years' retrospective single-center study
No full textInternational audienceBackground: After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not.Material/methods: In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM.Results: Over the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA-, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and - was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively).Conclusion: AML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results
New energy functionals for the incompressible Hall-MHD system
No full textWe show the existence and uniqueness of solutions to the threedimensional incompressible Hall-magnetohydrodynamic (Hall-MHD) system with initial data in critical Sobolev spaces. Our result works for general physical parameters, thus improves the partial result obtained very recently by Danchin and the author in [13] and fully answers a problem proposed by Chae and Lee in the Remark 2 of [6]. Considering the so-called 2.5D flows for the Hall-MHD system (that is 3D flows independent of the vertical variable), we show that under the sole assumption that the initial magnetic field is small in the critical Sobolev space leads to a global well-posedness statement
Immunoglobulin A Nephropathy in Association with Inflammatory Bowel Diseases: Results from a National Study and Systematic Literature Review
No full textInternational audienceAbstract Background Little is known about clinical characteristics and kidney outcomes in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). Methods We conducted a retrospective multicentre study with a centralized histological review to analyse the presentation, therapeutic management and outcome of 24 patients suffering from IBD-associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. Results Crohn's disease and ulcerative colitis accounted for 75 and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9\,years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. The urinary protein:creatinine ratio exceeded 100\,mg/mmol in 70.8% of patients (mean 254\,mg/mmol). Estimated glomerular filtration rate (eGFR) was >60\,mL/min/1.73\,m2 in 13/24 patients and only 1 patient required dialysis. In the Oxford mesangial hypercellularity, endocapillary cellularity, segmental sclerosis and interstitial fibrosis/tubular atrophy with crescents classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1\textendash 2 and 38% C1\textendash 2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2\,years, 4 patients (16.7%) had a poor kidney outcome: end-stage renal disease (n\,=\,3) or a >50% decrease in eGFR from initial values (n\,=\,1). A similar evolution was observed in patients with primitive IgAN. Conclusions This first case series suggests that IBD-associated IgAN has frequent inflammatory lesions at onset and variable long-term outcomes
Time to source control and outcome in community-acquired intra-abdominal infections The multicentre observational PERICOM study
No full textInternational audienceBACKGROUND Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment. OBJECTIVE To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes. DESIGN A prospective, multicentre, observational study. SETTING Thirteen teaching hospitals in France between April 2018 and February 2019. PATIENTS Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI. MAIN OUTCOME MEASURES The primary outcome was hospital length of stay. The secondary outcome was hospital mortality. RESULTS Patients had a mean age of 56 (+/- 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality. CONCLUSION This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated. STUDY REGISTRATION ClinicalTrials.gov on 1 April 2018, NCT03544203
Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine
No full textInternational audienceBackground SARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized. Methods We analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally. Results The first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4 + IL-2 + cells) and CD8 effector response (CD8 + IFNγ + cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection. Conclusions An analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies
Des villes au futur antérieur: Entretien avec Sylvain Allemand
No full textInternational audienceThis interview underlines the need for urban planners to think about a possible "past future". This approach is particularly relevant for Andean cities because of their own history, but also because of their very specific geography. Thinking of the city of the future without considering the city of the past can lead to aberrations, as is the case in Quito. Recent constructions, guided by the technological idol or the lure of profit, disregard the lessons that the archives give us in terms of volcanic eruptions or mudslides. Similarly, the construction of the metro has shown little respect for the pre-Hispanic remains, making the latent conflicts of memory in the city centre more acute. The role of the historian, through the Archival City programme, is therefore to tell the town planner that the city is above all a 'person' and that it deserves to be respected as such.Esta entrevista apunta la necesidad de que los urbanistas conciban las ciudades "en el futuro pasado". Algo muy relevante para las ciudades andinas de acuerdo con su propia historia, pero también con su geografía tan singular. Pensar en la ciudad del futuro sin tener en cuenta la ciudad del pasado puede dar lugar a aberraciones, como es el caso de Quito. Las construcciones recientes, guiadas por el ídolo tecnológico o el afán de lucro, han hecho caso omiso de las lecciones que nos dan los archivos en materia de erupciones volcánicas o de flujos de lodo. Asimismo, la construcción del metro ha sido poco respetuosa con los restos prehispánicos, agudizando los conflictos de memoria latentes en el centro de la ciudad. Por tanto, el papel del historiador, a través del programa Archival City, consiste en decir al urbanista que la ciudad es ante todo una "persona" y que merece ser respetada como tal.Cet entretien souligne la nécessité pour les urbanistes de penser les villes « au futur antérieur ». Une approche particulièrement pertinente pour les villes andines du fait d’une histoire propre, mais aussi, d’une géographie très singulière. Penser la ville du futur au mépris de celle du passé peut conduire à des aberrations, comme c’est le cas à Quito. Des constructions récentes, guidées par l’idole technologique ou l’appât du gain, y méprisent les enseignements que nous livrent les archives en matière d’éruptions volcaniques ou de coulées de boue. De même, la construction du métro a été peu respectueuse des vestiges préhispaniques, rendant plus aigus les conflits de mémoire latents dans le centre-ville. Le rôle de l’historien, par l’entremise du programme Archival City, est donc bien de dire à l’urbaniste que la ville est avant tout une « personne » et qu’elle mérite d’être respectée comme telle
Optimization of the Synthesis of Natural Polymeric Nanoparticles of Inulin Loaded with Quercetin: Characterization and Cytotoxicity Effect
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Graph Pattern Matching in GQL and SQL/PGQ
No full textInternational audienceAs graph databases become widespread, JTC1 -- the committee in joint charge of information technology standards for the International Organization for Standardization (ISO), and International Electrotechnical Commission (IEC) -- has approved a project to create GQL, a standard property graph query language. This complements a project to extend SQL with a new part, SQL/PGQ, which specifies how to define graph views over an SQL tabular schema, and to run read-only queries against them. Both projects have been assigned to the ISO/IEC JTC1 SC32 working group for Database Languages, WG3, which continues to maintain and enhance SQL as a whole. This common responsibility helps enforce a policy that the identical core of both PGQ and GQL is a graph pattern matching sub-language, here termed GPML. The WG3 design process is also analyzed by an academic working group, part of the Linked Data Benchmark Council (LDBC), whose task is to produce a formal semantics of these graph data languages, which complements their standard specifications. This paper, written by members of WG3 and LDBC, presents the key elements of the GPML of SQL/PGQ and GQL in advance of the publication of these new standards
Topological phase estimation method for reparameterized periodic functions
No full text31 pages, 14 figuresWe consider a signal composed of several periods of a periodic function, of which we observe a noisy reparametrisation. The phase estimation problem consists of finding that reparametrisation, and, in particular, the number of observed periods. Existing methods are well-suited to the setting where the periodic function is known, or at least, simple. We consider the case when it is unknown and we propose an estimation method based on the shape of the signal. We use the persistent homology of sublevel sets of the signal to capture the temporal structure of its local extrema. We infer the number of periods in the signal by counting points in the persistence diagram and their multiplicities. Using the estimated number of periods, we construct an estimator of the reparametrisation. It is based on counting the number of sufficiently prominent local minima in the signal. This work is motivated by a vehicle positioning problem, on which we evaluated the proposed method