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1.
Am J Hematol ; 99(6): 1095-1102, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581211

RESUMO

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation.


Assuntos
Inibidores de MTOR , Mastocitose Sistêmica , Sirolimo , Humanos , Mastocitose Sistêmica/tratamento farmacológico , Projetos Piloto , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , França , Idoso , Sirolimo/uso terapêutico , Sirolimo/efeitos adversos , Inibidores de MTOR/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Everolimo/uso terapêutico , Everolimo/efeitos adversos , Resultado do Tratamento , Serina-Treonina Quinases TOR/antagonistas & inibidores , Idoso de 80 Anos ou mais
2.
J Allergy Clin Immunol ; 153(1): 349-353.e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633651

RESUMO

BACKGROUND: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. OBJECTIVE: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. METHODS: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. RESULTS: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). CONCLUSION: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.


Assuntos
Anafilaxia , Mastocitose Sistêmica , Mastocitose , Humanos , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Estudos Retrospectivos , Prevalência , Mastocitose/epidemiologia , Mastocitose/genética , Mastocitose/patologia , Anafilaxia/patologia , Mastócitos/patologia , Triptases/genética
3.
Lancet Haematol ; 10(7): e521-e529, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37245522

RESUMO

BACKGROUND: CPX-351, an encapsulated form of cytarabine and daunorubicin, has shown greater efficacy than the classic 3 + 7 treatment administration in secondary acute myeloid leukaemia. Given that higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia share similarities with secondary acute myeloid leukaemia, we aimed to investigate the safety and efficacy of CPX-351 in this context. METHODS: This investigator-initiated two-cohort phase 2 trial was conducted by the Groupe Francophone des Myélodysplasies, with 12 participating centres in France. It comprised cohort A (reported here and completed), which included patients in first-line treatment, and cohort B, which was stopped for lack of inclusion (ie, not enough patients met the inclusion criteria), for patients with hypomethylating agent failure that is not reported here. Cohort A enrolled patients with newly diagnosed higher-risk myelodysplastic syndrome or chronic myelomonocytic leukaemia (aged 18-70 years old) with an Eastern Cooperative Oncology Group performance status of 0-1. Intravenous CPX-351 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) was given on days 1, 3, and 5, with a second induction cycle given (same daily dose on days 1 and 3) if at least a partial response was not reached. Patients who responded could receive up to four monthly consolidation cycles (same daily dose on day 1) or allogeneic haematopoietic stem-cell transplantation (HSCT). Overall response rate after one or two induction courses according to European LeukemiaNet 2017 acute myeloid leukaemia was the primary endpoint after CPX-351 induction, whether patients received one or two induction cycles. Safety was assessed in all patients enrolled (in cohort A). This trial is registered with ClinicalTrials.gov, NCT04273802. FINDINGS: Between April 29, 2020, and Feb 10, 2021, 21 (68%) male and ten (32%) female patients were enrolled. 27 (87%) of 31 patients responded (95% CI 70-96). 16 (52%) of the 31 patients received at least one consolidation cycle. 30 (97%) of the 31 patients included were initially considered eligible for allogeneic HSCT and 29 (94%) of the 31 patients had the procedure. Median follow-up was 16·1 months (IQR 8·3-18·1). The most common grade 3-4 adverse events were pulmonary (eight [26%] of 31 patients) and cardiovascular (six [19%] of 31 patients). There were 14 serious adverse events (mainly hospitalisation for infection [n=5] and only one was treatment-related) and no treatment-related death. INTERPRETATION: CPX-351 appears to be active and safe in patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia, allowing bridging to allogenic HSCT in most patients. FUNDING: Jazz Pharmaceuticals.


Assuntos
Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Citarabina , Daunorrubicina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Bull Cancer ; 110(2S): S97-S107, 2023 Feb.
Artigo em Francês | MEDLINE | ID: mdl-36658011

RESUMO

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 12th workshop on hematopoietic stem cell transplantation clinical practices harmonization procedures on September 2021 in Lille, France. In the absence of specific national or international recommendation, the French working group for autologous stem Cell transplantation in Auto-immune Diseases (MATHEC) proposed guidances for vaccinations of patients undergoing autologous hematopoietic stem cell transplantation for autoimmune disease, including in the context of SARS-Cov-2 pandemic.


Assuntos
Doenças Autoimunes , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Medula Óssea , Transplante Autólogo , COVID-19/prevenção & controle , SARS-CoV-2 , Doenças Autoimunes/terapia , Sociedades Médicas , Vacinação , França
5.
Support Care Cancer ; 31(2): 102, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622445

RESUMO

INTRODUCTION: Positive urine sample is a frequent finding in post-chemotherapy febrile neutropenia (FN) and can lead to prolonged antibiotic therapy. The aim of this study was to assess the outcome of bacteriuria episodes in FN patients receiving targeted antibiotic therapy. MATERIALS AND METHODS: A multi-centric retrospective study was conducted over a four-year period (2014-2019) on systematic urinalysis. All consecutive first bacteriuria episodes (≤ 2 bacteria with at least ≥ 103 CFU/mL) during FN in hospitalized adult patients for hematological malignancies were included. Relapse and recurrence were defined by fever or urinary tract symptoms (UTS) with the same bacterial subspecies in urine occurring ≤ 7 days and ≤ 30 days, respectively, after antibiotic discontinuation. Mortality rate was determined at 30 days. Targeted antibiotic therapy ≤ 10 days for women and ≤ 14 for men was considered as short course. RESULTS: Among 97 patients, 105 bacteriuria episodes on systematic urinalysis were analyzed; 67.6% occurred in women, 41.9% in AML patients, 17.1% were bacteremic, 14.2% presented with UTS, and 61.9% were treated with short-course antibiotic treatment. One death was reported. In men, no relapse/recurrence was noted, even in the short-course antibiotic group. In women, 2.8% of episodes treated with short-course antibiotic led to relapse or recurrence. CONCLUSIONS: Relapse, recurrence, and mortality were uncommon events in FN patients experiencing bacteriuria episode, whatever the antibiotic duration. To distinguish asymptomatic bacteriuria from infection remained challenging in women. In men, systematic urinalysis at onset of FN could be useful.


Assuntos
Bacteriúria , Neutropenia Febril , Hematologia , Infecções Urinárias , Adulto , Masculino , Humanos , Feminino , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Bacteriúria/diagnóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Antibacterianos/uso terapêutico , Febre/tratamento farmacológico , Febre/etiologia , Neutropenia Febril/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia
6.
J Clin Oncol ; 41(10): 1888-1897, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455187

RESUMO

PURPOSE: Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML). PATIENTS AND METHODS: Newly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression. RESULTS: One-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System-mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients (P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm (P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04). CONCLUSION: Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).


Assuntos
Leucemia Mielomonocítica Aguda , Leucemia Mielomonocítica Crônica , Humanos , Idoso , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/diagnóstico , Decitabina , Hidroxiureia/efeitos adversos , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Modelos de Riscos Proporcionais
7.
Cereb Cortex ; 33(4): 1300-1309, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35368078

RESUMO

Motivational congruency has been examined using tasks where participants perform approach or avoidance movements towards socially positive or negative faces. Language is tightly intertwined with interpersonal cognition. Thus, similar situations could be represented by means of language in interpersonal contexts: adjectives furnish valence to people (e.g. someone is cordial or arrogant), and attitudinal verbs define direction to relationship-actions: approach-avoidance (e.g. accept vs. reject). In an Electroencephalography (EEG) study, 40 participants were presented with sentences where a character was valenced (e.g. "Arthur is cordial/arrogant") before being the target of a relationship-actions ("Grisela welcomed/ignored Arthur at the party"). We analyzed both Event-related potential (ERP) amplitude and time-frequency power in response to the attitudinal verb. For ERP amplitudes, we found a significant cluster between 280 and 370 ms, covering part of the development of a N400-like ERP component. This cluster reflects an interaction driven by congruency between motivational direction and target valence. Likewise, time-frequency power analysis revealed an enhancement of theta rhythms under incongruent conditions, most likely indexing conflict processing. Results support that relationship-actions are represented as approach and avoidance and thus involve conflict processing and resolution of incongruent situations. Implications for the interweaving of affective language and social cognition within Embodiment Simulation Theory are discussed.


Assuntos
Eletroencefalografia , Potenciais Evocados , Humanos , Masculino , Feminino , Potenciais Evocados/fisiologia , Eletroencefalografia/métodos , Ritmo Teta , Idioma , Cognição
8.
Leukemia ; 36(10): 2519-2527, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36071100

RESUMO

The EUROPE phase 2 trial investigated the predictive value of biomarkers on the clinical efficacy of single agent romiplostim (ROM) treatment in patients with lower-risk myelodysplastic neoplasms (LR-MDS) and thrombocytopenia within the 'European Myelodysplastic Neoplasms Cooperative Group' (EMSCO) network. A total of 77 patients with LR-MDS and a median platelet count of 25/nl were included, all patients received ROM at a starting dose of 750 µg by SC injection weekly. Thirty-two patients (42%) achieved a hematologic improvement of platelets (HI-P) with a median duration of 340 days. Neutrophil (HI-N) and erythroid (HI-E) responses were observed in three (4%) and seven (9%) patients, respectively. We could not confirm previous reports that HI-P correlated with baseline endogenous thrombopoietin levels and platelet transfusion history, but SRSF2 mutation status and hemoglobin levels at baseline were significantly linked to HI-P. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response.


Assuntos
Síndromes Mielodisplásicas , Neoplasias , Biomarcadores , Hemoglobinas , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Neoplasias/tratamento farmacológico , Receptores Fc/genética , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/genética , Trombopoetina/uso terapêutico , Resultado do Tratamento
10.
J Infect ; 84(1): 1-7, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715238

RESUMO

OBJECTIVES: There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN. METHODS: This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation. RESULTS: Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005). CONCLUSION: Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies.


Assuntos
Bacteriemia , Neutropenia Febril , Leucemia Mieloide Aguda , Sepse , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Neutropenia Febril/complicações , Neutropenia Febril/tratamento farmacológico , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Sepse/tratamento farmacológico
11.
J Clin Immunol ; 42(1): 60-63, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596815

RESUMO

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.


Assuntos
Doença Granulomatosa Crônica , Hypocreales , Idoso , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Humanos , Pessoa de Meia-Idade , NADPH Oxidases/genética , Inativação do Cromossomo X
12.
Bull Cancer ; 107(12S): S140-S150, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33066955

RESUMO

Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.


Assuntos
Doença de Crohn/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Contraindicações de Procedimentos , Doença de Crohn/imunologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Seleção de Pacientes , Sociedades Médicas , Condicionamento Pré-Transplante , Transplante Homólogo
13.
Brain Sci ; 10(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751341

RESUMO

We examine the effect of transcranial direct current stimulation (tDCS) of right superior temporal sulcus (rSTS) in memorization of approach/avoidance relationship-action sentences; for example, "Alejandro accepted/rejected Marta in his group." Sixty-five university students participated in a tDCS study, in which a between-subjects design was adopted. Sixty-four participants were also given the behavioral approach system (BAS) and behavioral inhibition system (BIS) scales. Participants were subjected to 20 min of stimulation: anodal (N = 24), cathodal (N = 21), or sham (N = 20); subsequently, they were given a list of 40 sentences (half approach and half avoidance) and told to try to memorize them. Finally, they performed a changed/same memory task (half the sentences were the "same" and half were "changed"). Previously, we had examined performance in the memory task without tDCS with another group of participants (N = 20). We found that anodal stimulation improved d' index of discriminability (hits-false alarms) compared to sham and cathodal conditions for both approach and avoidance sentences. Moreover, the comparison between anodal and task-alone performance showed that stimulation improved d' index of approach sentences more, as task-alone performance showed better discrimination for avoidance than for approach. Likewise, we explored a potential modulation of tDCS effect by (BAS) and (BIS) traits. We found that d' index improvement in anodal stimulation condition only benefited low BAS and low BIS participants. Implications of these results are discussed in the context of rSTS function in encoding and memorizing verbally described intentional relationship-actions and the role of individual differences on modulating tDCS effect.

14.
PLoS One ; 15(6): e0234304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569322

RESUMO

Linguistic negation acts by inhibiting the representation of information under its scope, often leading to the representation of positive alternative states of affairs. Motivational direction refers to approach/avoidance intentionality in our interactions with environmental stimuli expressed by means of verbs (e.g., "accept" vs "reject"). We consider it plausible that negation interacts with direction to represent the true motivation of the protagonist in sentence understanding (e.g., if an approach action is negated it is represented as avoidance). In the first study, we examine this interaction offline by asking participants to judge approach or avoidance meaning of affirmative (e.g., "he/she included/excluded meat") and negative sentences ("he/she did not include/exclude meat"). Results support that negation reversed participants' interpretation of sentence motivational direction. In a further study, we carried out two probe recognition experiments to examine the interaction during sentence comprehension; in both, the critical probe was the word referring to the target of the action (e.g., "meat"). In the first experiment, participants had to recognize the probe word presented 1500 milliseconds after sentence offset, while for the second one, the delay was 500 milliseconds. Results showed that at 1500 ms, target recognition took significantly more time for negated avoidance sentences than for the other conditions. Therefore, representing negated avoidance sentences seems to imply more complex processing, as avoidance verbs would be implicitly negative. By contrast, at the 500 ms delay, negation impaired target recognition for both approach and avoidance sentences, suggesting an unspecific inhibitory effect of negation at that sentence processing stage. Implication of these results for both research on negation and in action understanding are discussed.


Assuntos
Compreensão , Motivação , Psicolinguística , Feminino , Humanos , Masculino , Adulto Jovem
16.
Bull Cancer ; 107(1S): S104-S113, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31818426

RESUMO

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/normas , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Condicionamento Pré-Transplante , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Transplante Autólogo
17.
Cancer Med ; 8(4): 1765-1770, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30848074

RESUMO

A large variety of molecular rearrangements of the NUP98 gene have been described in the past decades (n = 72), involving fusion partners coding for different transcription factors, chromatin modifying enzymes, as well as various cytosolic proteins. Here, we report the case of an AML-M2 patient with a variant NUP98-LEDGF/PSIP1 gene fusion (N9-L10). In this patient, three different NUP98-LEDGF fusion mRNAs were characterized due to alternative splicing in LEDGF exon 11. Targeted high-throughput sequencing revealed the presence of IDH1, SRSF2, and WT1 additional pathogenic mutations. To improve the therapeutic monitoring, quantification of NUP98-LEDGF mRNA by real-time PCR was developed. Because of poor response to conventional chemotherapy, allogeneic stem cell transplantation was performed, followed by 20 cycles of azacitidine-based preemptive treatment of relapse. More than 31 months after diagnosis, corresponding to 25 months post SCT and 4 months after the last cycle of azacytidine, the patient is in complete molecular remission (undetectable NUP98-LEDGF mRNA transcripts). This study highlights the considerable variability in breakpoint location within both NUP98 and LEDGF, associated with alternative splicing affecting LEDGF. It also emphasizes the need to fully characterize the breakpoints within the two genes and the identification of all fusion mRNAs, particularly for the development of a molecular monitoring assay. All these data seem critical for the optimal management of NUP98-LEDGF + hematological malignancies commonly associated with a poor prognosis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Leucemia Mieloide Aguda/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fatores de Transcrição/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Fusão Gênica , Rearranjo Gênico , Humanos , Cariótipo , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Indução de Remissão
18.
Bone Marrow Transplant ; 53(6): 749-755, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29523884

RESUMO

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m2) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m2 melphalan is a beneficial procedure for MM patients with renal failure.


Assuntos
Mieloma Múltiplo/terapia , Insuficiência Renal/terapia , Transplante Autólogo/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Insuficiência Renal/patologia , Estudos Retrospectivos
19.
Dement Neuropsychol ; 11(3): 262-269, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29213523

RESUMO

The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.


A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.

20.
Dement. neuropsychol ; 11(3): 262-269, July-Sept. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-891016

RESUMO

ABSTRACT The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.


RESUMO A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.


Assuntos
Humanos , Prevalência , Demência , Disfunção Cognitiva
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