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1.
Q J Exp Psychol (Hove) ; 75(1): 130-147, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34092150

RESUMO

The development of verbal fluency is associated with the maturation of executive function skills, such as the ability to inhibit irrelevant information, shift between tasks, and hold information in working memory. Some evidence suggests that multilinguistic upbringing may underpin disadvantages in verbal fluency and lexical retrieval, but can also afford executive function advantages beyond the language system including possible beneficial effects in older age. This study examined the relationship between verbal fluency and executive function in 324 individuals across the lifespan by assessing the developmental trajectories of English monolingual and multilingual children aged 7-15 years (N = 154) and adults from 18 to 80 years old (N = 170). The childhood data indicated patterns of improvement in verbal fluency and executive function skills as a function of age. Multilingual and monolingual children had comparable developmental trajectories in all linguistic and non-linguistic measures used in the study with the exception of planning, for which monolingual children showed a steeper improvement over the studied age range relative to multilingual children. For adults, monolinguals and multilingual participants had comparable performance on all measures with the exception of nonverbal inhibitory control and response times on the Tower of London task: monolinguals showed a steeper decline associated with age. Exploratory factor analysis indicated that verbal fluency was associated with working memory and fluid intelligence in monolingual participants but not in multilinguals. These findings raise the possibility that early acquisition of an additional language may impact on the development of the functional architecture serving high-level human cognition.


Assuntos
Função Executiva , Multilinguismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Humanos , Idioma , Testes de Linguagem , Pessoa de Meia-Idade , Adulto Jovem
2.
J Nucl Med ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740949

RESUMO

Aim: To evaluate the prognostic value of somatostatin receptor tumor burden (SRTB) at 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumors (WD-NETs). Methods: We retrospectively analyzed 68Ga-DOTATOC-PET/CT of 84 patients with histologically confirmed WD-NETs (51 G1, 30 G2 and 3 G3). For each PET/CT, all DOTATOC-avid lesions were independently segmented by 2 operators using a customized threshold based on the healthy liver maximum standardized uptake value (SUVmax) using LIFEx 5.1. Somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE=SRETV*SUVmean) were extracted for each lesion and then whole-body SRETV and TLSRE (SRETVwb and TLSREwb) were defined as the sum of SRETV and TLSRE of all segmented lesions in each patient, respectively. Time to progression (TTP) was defined as the combination of disease-free-survival in patients undergoing curative surgery (n = 10) and progression-free survival for patients with unresectable/metastatic disease (n = 74). TTP and overall survival (OS) were calculated by Kaplan-Meier analysis, log-rank test, and Cox's proportional hazard model. Results: After a median follow-up period of 15.5 months disease progression was confirmed in 35 patients (41.7%) and 14 patients died. Higher SRETVwb (>39.1ml) and TLSREwb (>306.8g) were significantly correlated with shorter median TTP (TTP = 12months vs not reached; p<0.001). In multivariate analysis, SRETVwb (P = 0.005) was the only independent predictor of TTP regardless of histopathologic grade and TNM staging. Conclusion: According to our results, SRETVwb and TLSREwb extracted from 68Ga-DOTATOC-PET/CT could predict TTP/OS and might have an important clinical utility in the management of in patients with WD-NETs.

3.
Front Oncol ; 11: 712053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778029

RESUMO

Background: Few data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available. Methods: This multicenter, retrospective study aimed at evaluating clinicians' attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: progression-free survival (PFS), overall survival (OS), adverse events, and objective response rate (ORR). Results: At the data cutoff, among 686 consecutive patients with left-sided RAS/BRAF wild-type mCRC treated with doublet plus anti-EGFR as first-line regimen from March 2012 to October 2020, 355 eligible patients have been included in the present analysis. Among these, 118 (33.2%), 66 (18.6%), and 11 (3.1%) received a maintenance with 5-fluorouracil/leucovorin (5FU/LV)+anti-EGFR, anti-EGFR, and 5FU/LV, respectively, while 160 (45.1%) patients continued induction treatment (non-maintenance) until disease progression, unacceptable toxicity, patient decision, or completion of planned treatment. The median period of follow-up for the overall population was 33.7 months (95%CI = 28.9-35.6). The median PFS values of the 5FU/LV+anti-EGFR, anti-EGFR, 5FU/LV, and non-maintenance cohorts were 16.0 (95%CI = 14.3-17.7, 86 events), 13.0 (95%CI = 11.4-14.5, 56 events), 14.0 (95%CI = 8.1-20.0, 8 events), and 10.1 months (95%CI = 9.0-11.2, 136 events), respectively (p < 0.001). The median OS values were 39.6 (95%CI = 31.5-47.7, 43 events), 36.1 (95%CI = 31.6-40.7, 36 events), 39.5 (95%CI = 28.2-50.8, 4 events), and 25.1 months (95%CI = 22.6-27.6, 99 events), respectively (p < 0.001). After adjusting for key covariates, a statistically significant improvement in PFS in favor of 5FU/LV+anti-EGFR (HR = 0.59, 95%CI = 0.44-0.77, p < 0.001) and anti-EGFR (HR = 0.71, 95%CI = 0.51-0.98, p = 0.039) compared to the non-maintenance cohort was found. Compared to the non-maintenance cohort, OS was improved by 5FU/LV+anti-EGFR (HR = 0.55, 95%CI = 0.38-0.81, p = 0.002) and, with marginal significance, by anti-EGFR (HR = 0.67, 95%CI = 0.51-0.98, p = 0.051). No difference was found in ORR. Any grade non-hematological and hematological events were generally higher in the non-maintenance compared to the maintenance cohorts. Conclusion: Among the treatment strategies following an anti-EGFR-based doublet first-line induction regimen in patients affected by left-sided RAS/BRAF wild-type mCRC treated in a "real-life" setting, 5FU/LV+anti-EGFR resulted the most adopted, effective, and relatively safe regimen.

4.
Support Care Cancer ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779921

RESUMO

BACKGROUND: Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines have only recently been published. AIM AND METHODS: To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%, p < 0.001) and in patients treated with panitumumab (76.1% vs 93.7%, p < 0.001) or cetuximab (83.3% vs 95.4%, p = 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%, p = 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%, p = 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively, p = 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively, p < 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months). CONCLUSION: Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients' quality of life without compromising the continuity and efficacy of antineoplastic therapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34380594

RESUMO

BACKGROUND: Doublets plus antiepidermal growth factor receptors monoclonal antibodies (EGFRi) are widely considered the preferable first-line regimen in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC), resulting superior in terms of activity and efficacy compared to doublets plus bevacizumab. However, data comparing doublet plus EGFRi and triplet plus bevacizumab are lacking, and the relative benefit of an intensive regimen plus an antiangiogenic backbone in this population is debated. METHODS: This multicenter, retrospective study aimed at evaluating clinicians' attitude to triplet-bevacizumab and doublet-EGFRi as first-line regimen in patients with left-sided RAS/BRAF wild-type mCRC treated in clinical practice at 22 Oncology Units from March 2012 to October 2020. A random case-control matching was performed to compare activity (ORR), and effectiveness (PFS, OS, secondary resection rate of metastases with curative intent) between triplet-bevacizumab and doublet-EGFRi, on the basis of ECOG-PS, age, gender, and burden of disease. RESULTS: A total of 718 patients were consecutively treated with doublet-EGFRi (686, 95.5%) or triplet-bevacizumab (32, 4.5%). After case-control matching, median PFS was 13.6 (95% CI, 8.9-31.7) and 16.1 (95% CI, 12.1-36.8) months (P= .621), while median OS was 30.2 (95% CI, 14.4-69.5) and 38.1 (95% CI, 33.1-101.1) months (P= .0283) in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. The ORR was 65.6% and 90.6% (P= .016), while the secondary resection rate was 18.8% and 46.9% (P= .016), in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. Triplet-bevacizumab was associated with a higher incidence of G3/G4 neutropenia (25.0% vs. 12.5%, P= .041). CONCLUSION: Although a doublet-EGFRi remains the recommended upfront regimen in patients with left-sided RAS and BRAF wild-type mCRC, our real life data suggest a triplet-bevacizumab might be at least equally active and effective in properly selected cases.

7.
Acta Oncol ; 60(10): 1317-1324, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34282710

RESUMO

BACKGROUND: Standard treatment of advanced biliary tract cancer (aBTC) is represented by first-line chemotherapy (CT1). However, some patients do not gain any benefit from CT1, contributing to the overall dismal prognosis of aBTC. The present study aimed to devise a prognostic model in aBTC patients receiving CT1. METHODS: A large panel of clinical, laboratory, and pathology variables, available before the start of CT1, were retrospectively assessed in a multi-centric cohort to determine their prognostic value on univariate and multivariate regression analysis. The variables that showed a significant correlation with overall survival (OS) were computed in a three-tier prognostic score. External validation of the prognostication performance was carried out. RESULTS: Clinical histories of 935 patients (median OS 10.3 months), with diagnosis dates ranging from 2001 to 2017, were retrieved from 14 institutions. According to multivariate analysis, Eastern Cooperative Oncology Group performance status, carbohydrate antigen 19.9, albumin levels, and neutrophil/lymphocyte ratio were strongly associated with OS (p <0.01). The prognostic score could generate a highly significant stratification (all between-group p values ≤0.001) into groups of favorable (comprising 51.5% of the sample), intermediate (39.2%), and poor prognosis (9.3%): median OS was 12.7 (CI95% 11.0-14.4), 7.1 (CI95% 5.8-8.4), and 3.2 months (CI95% 1.7-4.7), respectively. This OS gradient was replicated in the validation set (129 patients), with median OS of 12.7 (CI95% 11.0-14.3), 7.5 (CI95% 6.1-8.9), and 1.4 months (CI95% 0.1-2.7), respectively (all between-group p values ≤0.05). CONCLUSION: A prognostic score, derived from a limited set of easily-retrievable variables, efficiently stratified a large population of unselected aBTC patients undergoing CT1. This tool could be useful to clinicians, to ascertain the potential benefit from CT1 at the start of treatment.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar/tratamento farmacológico , Humanos , Linfócitos , Prognóstico , Estudos Retrospectivos
8.
J Chemother ; : 1-10, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313188

RESUMO

Advanced biliary tract cancer (aBTC) comprises a heterogeneous group of rare malignancies with dismal prognosis. Given the scarcity of prospective evidence, the aim of this study was to derive clinically useful insights and prognostic factors from a large, real-world series of aBTC. Clinicopathologic variables and treatment outcomes were retrospectively collected involving 940 patients diagnosed with aBTC between 2001 and 2017, and treated with first-line chemotherapy (CT1) at 14 Italian medical oncology institutions. Median overall survival (OS) was 10.3 months (CI95% 9.5-11.1). CT1 with gemcitabine-Platinum salts doublets achieved OS of 11.7 months vs 7.5 with gemcitabine alone (HR 0.67, p < 0.001). However, a clear temporal trend towards improved OS could not be demonstrated. Radical surgery of recurrent disease achieved a relapse-free survival of 5.9 months. A substantial minority (44.5%) of patients were able to receive a second-line chemotherapy, which achieved a response rate of 7.6%, and disease control in 30% of patients with no significant differences between combination regimens and monotherapies. In a large retrospective series of real-world aBTC, outcomes of standard CT1 closely resembled those of the registrational trials. A limited set of easily retrievable independent prognostic factors was defined. Further research is needed on second-line regimens.

9.
Res Child Adolesc Psychopathol ; 49(11): 1403-1417, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34152501

RESUMO

It has been proposed that enhancing motivation supports the learning of children with Attention Deficit Hyperactivity Disorder (ADHD). Less is known if inattentive children with no ADHD diagnosis may similarly benefit, when being motivated to engage in an academic task. Using a repeated-measures design, this study investigated the effects of text choice as an intrinsic motivator on the reading comprehension and enjoyment of Year 4 children attending mainstream primary schools (N = 92; aged 8-9 years; 48 boys); comparing those with no attentional difficulties and severe inattention. We hypothesized that 1) choice would increase reading comprehension and enjoyment 2) choice would increase the reading comprehension and enjoyment of children both with severe inattention and no attentional difficulties 3) choice effects would be significantly greater for children with severe inattention than those with no attentional difficulties. Children participated in a reading intervention that included a Choice (experimental) and a No Choice (control) condition. Child inattention was measured via a Virtual Reality Continuous Performance Task (Omission errors, Reaction Time Variability) and Teacher Ratings. Choice significantly increased reading comprehension, but not enjoyment compared with no choice. Choice improved the reading comprehension of children with both severe inattention and no attentional difficulties. Choice did not benefit the reading of severely inattentive children more than that of children with no attentional difficulties. These findings underline the educational benefits of choice for young readers both with severe inattention and no attentional difficulties, which are further discussed drawing on existing theory and research.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Leitura , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Compreensão , Humanos , Aprendizagem , Masculino , Prazer
10.
Artigo em Inglês | MEDLINE | ID: mdl-34033000

RESUMO

BACKGROUND AND AIM: The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemotherapy is compelling. The aim of the study is to evaluate the ECSIPOT (psECogSIiPnigOT) index, influenced by PECS (PsECogSii) index, prognostic nutritional index (PNI), and GOT. METHODS: This international study was conducted on a training cohort of 126 patients and in three validation cohorts, both European and Korean. ECSIPOT index formula: (PECS:0 = 1 point; PECS:1 = 1.4 points; PECS:2 = 3.2 points) + (PNI > 36.7 = 1 point; PNI < 36.7 = 2 points) + (GOT < 100 = 1 point; GOT > 100 = 2 points). Event-time distributions were estimated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: In the training cohort, mOS was 12.9, 6.3, and 2.8 months for patients with ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 2.11; ECSIPOT-2: HR 4.93; p < 0.0001). In the first validation cohort, mOS was 11.5, 7.3, and 3.3 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 1.74; ECSIPOT-2: HR 3.41; p < 0.0001). In the second validation cohort, mOS was 25.2, 12.5, and 3.0 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 2.33; ECSIPOT-2: HR 8.46; p < 0.0001). In the third validation cohort, mOS was 11.8, 8.1, and 4.6 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 1.47; ECSIPOT-2: HR 3.17; p < 0.0001). Multivariate analysis in all cohorts confirmed the ECSIPOT index as an independent prognostic factor for OS. CONCLUSION: The easy assessment and good risk-stratification performance make the ECSIPOT index a promising tool to comprehensively estimate the prognosis of aBTC patients.

11.
Trials ; 22(1): 205, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712055

RESUMO

BACKGROUND: The burnout phenomenon has been extensively investigated among health care professionals, particularly focusing on physicians and nurses. However, literature concerning burnout in clinical research is poor and often neglects the other professional categories involved. METHODS: In March 2019, all members of Italian Group of Clinical Research Coordinator were invited to participate to a web survey, consisting of three sections: general information and workload; Maslach Burnout Inventory (MBI) test; subjective perception of oneself's work stress and possible causes. RESULTS: The majority of respondents felt a form of distress. The main source was contract type (31.2%), followed by workload (20.5%) and lack of skills recognition (17.8%). Results from MBI test confirmed the interviewees' subjective perception: an intermediate level of emotional exhaustion (19.1 points) and a very high sense of reduced professional achievement (26.8 points) were observed. Both depersonalization and sense of reduced professional achievement showed weak to moderate correlations with emotional exhaustion. Emotional exhaustion was associated with contract type with high significance. CONCLUSION: It is necessary to act on those qualitative factors that are greatly increasing the level of perceived stress, jeopardizing the quality of clinical research coordinators work and significantly amplifying the phenomenon of migration towards the private sector.


Assuntos
Esgotamento Profissional , Médicos , Esgotamento Profissional/diagnóstico , Esgotamento Profissional/epidemiologia , Humanos , Itália , Inquéritos e Questionários , Carga de Trabalho
12.
Artigo em Inglês | MEDLINE | ID: mdl-33544375

RESUMO

BACKGROUND AND AIM: The aim of the present study is to evaluate a new index (PECS (PsECogSii)index) influenced by PS ECOG and systemic immune-inflammation index (SII) in unresectable locally advanced or metastatic BTC patients treated with first-line chemotherapy. METHODS: This multicenter, international, study was conducted on a training cohort of 130 patients and in three European and Korean validation cohorts The PECS index was calculated as ECOG × SII index (neutrophil count × platelet count/lymphocyte count). Event-time distributions were estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. RESULTS: In the training cohort, the median overall survival (mOS) was 13.2 months, 8.7 months, and 3.8 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 1.41; PECS-2: HR 3.23) (p < 0.0001). In the first validation cohort, the mOS was 12.8 months, 10.1 months, and 5.3 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 1.29; PECS-2: HR 2.40) (p < 0.0001). In the second validation cohort, the mOS was 21.2 months, 10.2 months, and 3.0 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 2.25; PECS-2: HR 9.00) (p < 0.0001). In the third validation cohort, the median OS was 15.5 months, 7.5 months, and 3.7 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: ref HR = 1; PECS-1: HR 2.14; PECS-2: HR 5.00) (p < 0.0001). Multivariate analysis in all cohorts confirmed the PECS index as an independent prognostic factor for OS. CONCLUSIONS: The easy assessment, low cost, and reproducibility make PECS index a promising tool to assess the prognosis of BTC patients in future clinical practice.

13.
Expert Opin Pharmacother ; 22(6): 677-684, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33576301

RESUMO

Introduction: Characteristic of some rare pediatric and adult malignancies, addiction to the NTRK oncogene family is also observed in a small fraction of common cancers. Inhibition of their protein products, the Trk kinases, proved a successful treatment strategy for these tumors.Areas covered: The current paper reviews the clinical development of larotrectinib, a selective inhibitor of the Trk kinase family, for the treatment of NTRK fusion-positive cancers. The manuscript includes an overview of the efficacy, safety, pharmacokinetics and pharmacodynamics. The authors sum up by providing the reader with their expert opinion on larotrectinib and its potential future use.Expert opinion: Larotrectinib showed tolerability and high efficacy, regardless of the primary site. In 2018, larotrectinib was granted by the Food and Drug Administration a tissue-agnostic approval for the treatment of solid tumors harboring an NTRK fusion. The major challenges will be the implementation of the screening for NTRK fusions in the general oncologic population, and the incorporation of larotrectinib into the therapeutic algorithms.


Assuntos
Neoplasias , Inibidores de Proteínas Quinases , Adulto , Criança , Fusão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis , Pirimidinas
14.
Oncology ; 99(5): 292-299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626532

RESUMO

BACKGROUND AND AIMS: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. METHODS: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. RESULTS: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32-0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52-0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26-0.73, p = 0.0016). CONCLUSIONS: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Int J Cancer ; 147(11): 3177-3188, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525595

RESUMO

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Irinotecano/administração & dosagem , Platina/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , França , Humanos , Irinotecano/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Platina/uso terapêutico , Estudos Prospectivos , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
16.
Q J Exp Psychol (Hove) ; 73(11): 1757-1773, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32419614

RESUMO

The modern understanding of the term metacognition encompasses two levels of processing: a lower level awareness or knowledge of one's own thoughts and a higher level regulation or control of our thinking. Metacognition, therefore, bears conceptual similarity with executive function: both are concerned with top-down monitoring and control of cognition in the service of ongoing goal-directed behaviour. Previous studies have shown a possible executive function advantage in multilingual speakers but also a possible disadvantage in metacognitive processing. To progress theory on metacognitive processing and the relationship with executive function and linguistic experience across the lifespan, we conducted a study testing 330 healthy individuals in four age groups from 7 to 80 years old. All participants performed a metacognition task and two measures of executive function, which included the Simon task and the Tower of London task. Half the participants were multilingual speakers since birth. We built developmental trajectories of metacognitive and executive function across the lifespan. The best metacognitive efficiency was observed in mid-adulthood, whereas the best executive function processing reached its peak in young adulthood. A steep cognitive decline was observed in older age, while metacognitive efficiency was preserved. Exploratory factor analysis indicated that metacognition and executive function are served by different factors across all ages. Contrary to previous findings in the bilingual literature, a multilinguistic experience conferred neither any significant advantage nor disadvantage in both executive function and metacognitive processing across the lifespan.


Assuntos
Função Executiva , Metacognição , Multilinguismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem
17.
PLoS One ; 15(4): e0231288, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315339

RESUMO

We evaluate brain structure sensitivity to verbal interference in a sentence interpretation task, building on previously reported evidence that those with better control of verbal interference show higher grey matter density in the posterior paravermis of the right cerebellum. We compare brain structure sensitivity to verbal interference control across two groups, English monolingual (N = 41) and multilingual (N = 46) adults. Using voxel-based morphometry, our primary goal was to identify and explore differences in regional patterns of grey matter sensitivity to performance on the sentence interpretation task, controlling for group variability in age, nonverbal reasoning and vocabulary knowledge. There was no group difference in performance but there was a significant group effect in grey matter sensitivity to task performance in our region of interest: stronger sensitivity in the paravermis in bilinguals compared to monolinguals in accuracy performance in the high (relative to low) verbal interference condition. This effect was observed when the linguistic interference was presented in an unfamiliar language (Greek) but not when presented in the familiar language (English). Our findings suggest that multilanguage acquisition mediates regional involvement within the language network, conferring enhanced functional plasticity within structures (including the paravermis) in the service of control of linguistic interference.


Assuntos
Substância Cinzenta/fisiologia , Multilinguismo , Percepção da Fala , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
18.
Cognition ; 200: 104252, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32151855

RESUMO

Research on speech comprehension in noise indicates that a multilinguistic experience may confer advantages in filtering out verbal interference, an effect observed both in children acquiring two or more languages since birth (Filippi, Morris, Richardson, et al., 2015) and in second language learner adults (Filippi, Leech, Thomas, et al., 2012). A possible interpretation for this advantage is that the multilingual mind is "trained" to control interference from the language not in use. This constant effort may support optimization of cognitive resources that are necessary for successfully selecting, processing and interpreting complex linguistic information. The present study aimed to extend this line of research by including a non-verbal interference condition. 209 typically developing children (132 English monolinguals and 77 multilinguals from different linguistic backgrounds) carried out a sentence interpretation task in the presence of verbal and non-verbal interference. We found no evidence for a reliable group difference in our data. Instead, findings indicated that background cognitive ability and socioeconomic status were the best indicators of successful control of interference, irrespective of whether participants were bilingual or monolingual. These findings are discussed in the light of previous research and, more widely, on the account of the current debate on the bilingual advantage.


Assuntos
Multilinguismo , Percepção da Fala , Adulto , Criança , Compreensão , Humanos , Idioma , Fala
19.
Oncologist ; 25(6): 481-487, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31967692

RESUMO

BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking. PATIENTS AND METHODS: Data and samples from 85 patients with MSI-H mCRC treated with ICIs were gathered. Tumor infiltrating lymphocytes (TILs) and tumor mutational burden (TMB) were analyzed in an exploratory cohort of "super" responders and "clearly" refractory patients; TILs were then evaluated in the whole cohort of patients. Primary objectives were the correlation between the number of TILs and TMB and their role as biomarkers of ICI efficacy. Main endpoints included response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: In the exploratory cohort, an increasing number of TILs correlated to higher TMB (Pearson's test, p = .0429). In the whole cohort, median number of TILs was 3.6 in responders compared with 1.8 in nonresponders (Mann-Whitney test, p = .0448). RR was 70.6% in patients with high number of TILs (TILs-H) compared with 42.9% in patients with low number of TILs (odds ratio = 3.20, p = .0291). Survival outcomes differed significantly in favor of TILs-H (PFS: hazard ratio [HR] = 0.42, p = .0278; OS: HR = 0.41, p = .0463). CONCLUSION: A significant correlation between higher TMB and increased number of TILs was shown. A significantly higher activity and better PFS and OS with ICI in MSI-H mCRC were reported in cases with high number of TILs, thus supporting further studies of TIL count as predictive biomarker of ICI efficacy. IMPLICATIONS FOR PRACTICE: Microsatellite instability is the result of mismatch repair protein deficiency, caused by germline mutations or somatic modifications in mismatch repair genes. In metastatic colorectal cancer (mCRC), immunotherapy (with immune checkpoint inhibitors [ICIs]) demonstrated remarkable clinical benefit in microsatellite instability-high (MSI-H) patients. ICI primary resistance has been observed in approximately 25% of patients with MSI-H mCRC, underlining the need for predictive biomarkers. In this study, tumor mutational burden (TMB) and tumor infiltrating lymphocyte (TIL) analyses were performed in an exploratory cohort of patients with MSI-H mCRC treated with ICIs, demonstrating a significant correlation between higher TMB and increased number of TILs. Results also demonstrated a significant correlation between high number of TILs and clinical responses and survival benefit in a large data set of patients with MSI-H mCRC treated with ICI. TMB and TILs could represent predictive biomarkers of ICI efficacy in MSI-H mCRC and should be incorporated in future trials testing checkpoint inhibitors in colorectal cancer.


Assuntos
Neoplasias Colorretais , Linfócitos do Interstício Tumoral , Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Humanos , Instabilidade de Microssatélites
20.
Liver Int ; 40(3): 704-711, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31773848

RESUMO

BACKGROUND: An accurate risk-stratification is key to optimize the benefit-to-risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first-line chemotherapy. METHODS: Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS). RESULTS: 114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut-off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P = .0011), together with increased NLR (P = .0046) and ECOG >1 (P < .0001). The median OS was 5.4 vs 12.1 months in the low- vs high PNI-group. Moreover, a PNI value >36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC. CONCLUSIONS: We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first-line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.


Assuntos
Neoplasias , Avaliação Nutricional , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos
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