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1.
Radiol Med ; 129(5): 807-816, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38512624

RESUMO

OBJECTIVES: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. MATERIALS AND METHODS: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. RESULTS: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. CONCLUSION: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Tomografia Computadorizada de Feixe Cônico , Meios de Contraste , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Tomografia Computadorizada de Feixe Cônico/métodos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Quimioembolização Terapêutica/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Terapia Combinada , Valor Preditivo dos Testes , Óleo Etiodado/administração & dosagem
2.
Sensors (Basel) ; 23(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37631560

RESUMO

Active magnetic bearings are complex mechatronic systems that consist of mechanical, electrical, and software parts, unlike classical rolling bearings. Given the complexity of this type of system, fault detection is a critical process. This paper presents a new and easy way to detect faults based on the use of a fault dictionary and machine learning. The dictionary was built starting from fault signatures consisting of images obtained from the signals available in the system. Subsequently, a convolutional neural network was trained to recognize such fault signature images. The objective of this study was to develop a fault dictionary and a classifier to recognize the most frequent soft electrical faults that affect position sensors and actuators. The proposed method permits, in a computationally convenient way that can be implemented in real time, the determination of which component has failed and what kind of failure has occurred. Therefore, this fault identification system allows determining which countermeasure to adopt in order to enhance the reliability of the system. The performance of this method was assessed by means of a case study concerning a real turbomachine supported by two active magnetic bearings for the oil and gas field. Seventeen fault classes were considered, and the neural network fault classifier reached an accuracy of 93% on the test dataset.

3.
J Neurosci ; 41(14): 3234-3253, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33622775

RESUMO

Popular models of decision-making propose that noisy sensory evidence accumulates until reaching a bound. Behavioral evidence as well as trial-averaged ramping of neuronal activity in sensorimotor regions of the brain support this idea. However, averaging activity across trials can mask other processes, such as rapid shifts in decision commitment, calling into question the hypothesis that evidence accumulation is encoded by delay period activity of individual neurons. We mined two sets of data from experiments in four monkeys in which we recorded from superior colliculus neurons during two different decision-making tasks and a delayed saccade task. We applied second-order statistical measures and spike train simulations to determine whether spiking statistics were similar or different in the different tasks and monkeys, despite similar trial-averaged activity across tasks and monkeys. During a motion direction discrimination task, single-trial delay period activity behaved statistically consistent with accumulation. During an orientation detection task, the activity behaved superficially like accumulation, but statistically consistent with stepping. Simulations confirmed both findings. Importantly, during a simple saccade task, with similar trial-averaged activity, neither process explained spiking activity, ruling out interpretations based on differences in attention, reward, or motor planning. These results highlight the need for exploring single-trial spiking dynamics to understand cognitive processing and raise the interesting hypothesis that the superior colliculus participates in different aspects of decision-making depending on task differences.SIGNIFICANCE STATEMENT How are decisions based on sensory information transformed into actions? We report that single-trial neuronal activity dynamics in the superior colliculus of monkeys show differences in decision-making tasks depending on task idiosyncrasies and requirements and despite similar trial-averaged ramping activity. These results highlight the importance of exploring single-trial spiking dynamics to understand cognitive processing and raise the interesting hypothesis that the superior colliculus participates in different aspects of decision-making depending on task requirements.


Assuntos
Potenciais de Ação/fisiologia , Tomada de Decisões/fisiologia , Percepção de Movimento/fisiologia , Neurônios/fisiologia , Colículos Superiores/fisiologia , Animais , Macaca mulatta , Masculino , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Movimentos Sacádicos/fisiologia
4.
Cancer Immunol Immunother ; 71(1): 45-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34009410

RESUMO

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy.


Assuntos
Antígeno B7-H1/biossíntese , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Neoplasias Gástricas/diagnóstico , Idoso , Antineoplásicos/farmacologia , Feminino , Herpesvirus Humano 4 , Humanos , Imuno-Histoquímica , Imunoterapia , Inflamação , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Período Perioperatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Microambiente Tumoral
5.
PLoS Comput Biol ; 17(3): e1008779, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33780449

RESUMO

Current dominant views hold that perceptual confidence reflects the probability that a decision is correct. Although these views have enjoyed some empirical support, recent behavioral results indicate that confidence and the probability of being correct can be dissociated. An alternative hypothesis suggests that confidence instead reflects the magnitude of evidence in favor of a decision while being relatively insensitive to the evidence opposing the decision. We considered how this alternative hypothesis might be biologically instantiated by developing a simple neural network model incorporating a known property of sensory neurons: tuned inhibition. The key idea of the model is that the level of inhibition that each accumulator unit receives from units with the opposite tuning preference, i.e. its inhibition 'tuning', dictates its contribution to perceptual decisions versus confidence judgments, such that units with higher tuned inhibition (computing relative evidence for different perceptual interpretations) determine perceptual discrimination decisions, and units with lower tuned inhibition (computing absolute evidence) determine confidence. We demonstrate that this biologically plausible model can account for several counterintuitive findings reported in the literature where confidence and decision accuracy dissociate. By comparing model fits, we further demonstrate that a full complement of behavioral data across several previously published experimental results-including accuracy, reaction time, mean confidence, and metacognitive sensitivity-is best accounted for when confidence is computed from units without, rather than units with, tuned inhibition. Finally, we discuss predictions of our results and model for future neurobiological studies. These findings suggest that the brain has developed and implements this alternative, heuristic theory of perceptual confidence computation by relying on the diversity of neural resources available.


Assuntos
Tomada de Decisões/fisiologia , Modelos Neurológicos , Redes Neurais de Computação , Animais , Biologia Computacional , Inibição Psicológica , Macaca mulatta , Masculino , Percepção/fisiologia , Tempo de Reação/fisiologia , Colículos Superiores/fisiologia
6.
Neuroimage ; 229: 117700, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418072

RESUMO

Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care ("culture of care") and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research.


Assuntos
Acesso à Informação/ética , Bem-Estar do Animal/ética , Pesquisa Biomédica/ética , Internacionalidade , Neurociências/ética , Bem-Estar do Animal/legislação & jurisprudência , Animais , Pesquisa Biomédica/legislação & jurisprudência , Membro de Comitê , Humanos , Neurociências/legislação & jurisprudência , Primatas
7.
Proc Natl Acad Sci U S A ; 115(7): E1588-E1597, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29382765

RESUMO

Recent studies suggest that neurons in sensorimotor circuits involved in perceptual decision-making also play a role in decision confidence. In these studies, confidence is often considered to be an optimal readout of the probability that a decision is correct. However, the information leading to decision accuracy and the report of confidence often covaried, leaving open the possibility that there are actually two dissociable signal types in the brain: signals that correlate with decision accuracy (optimal confidence) and signals that correlate with subjects' behavioral reports of confidence (subjective confidence). We recorded neuronal activity from a sensorimotor decision area, the superior colliculus (SC) of monkeys, while they performed two different tasks. In our first task, decision accuracy and confidence covaried, as in previous studies. In our second task, we implemented a motion discrimination task with stimuli that were matched for decision accuracy but produced different levels of confidence, as reflected by behavioral reports. We used a multivariate decoder to predict monkeys' choices from neuronal population activity. As in previous studies on perceptual decision-making mechanisms, we found that neuronal decoding performance increased as decision accuracy increased. However, when decision accuracy was matched, performance of the decoder was similar between high and low subjective confidence conditions. These results show that the SC likely signals optimal decision confidence similar to previously reported cortical mechanisms, but is unlikely to play a critical role in subjective confidence. The results also motivate future investigations to determine where in the brain signals related to subjective confidence reside.


Assuntos
Comportamento de Escolha , Neurônios/fisiologia , Colículos Superiores/fisiologia , Animais , Tomada de Decisões , Macaca mulatta , Masculino
8.
Sensors (Basel) ; 21(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34451036

RESUMO

A self-oscillating microcantilever in a feedback loop comprised of a gain, a saturator, and an adjustable phase-shifter is used to measure the viscosity of Newtonian fluids. Shifting the signal of the loop with the adjustable phase-shifter causes sudden jumps in the oscillation frequency of the cantilever. The exact position of these jumps depends on whether the shift imposed by the phase-shifter is increasing or decreasing and, therefore, the self-excited cantilever exhibits a hysteretic non-linear response. This response was studied and the system modeled by a delay differential equation of motion where frequency-dependent added mass and damping terms accounted for the density and the viscosity of the medium. Experimental data were obtained for solutions with different concentrations of glycerol in water and used to validate the model. Two distinct sensing modalities were proposed for this system: the sweeping mode, where the width of the observed hysteresis depends on the viscosity of the medium, and the threshold mode, where a sudden jump of the oscillation frequency is triggered by an arbitrarily small change in the viscosity of the medium.

9.
Sensors (Basel) ; 21(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429920

RESUMO

In this paper, solutions for precise maneuvering of an autonomous small (e.g., 350-class) Unmanned Aerial Vehicles (UAVs) are designed and implemented from smart modifications of non expensive mass market technologies. The considered class of vehicles suffers from light load, and, therefore, only a limited amount of sensors and computing devices can be installed on-board. Then, to make the prototype capable of moving autonomously along a fixed trajectory, a "cyber-pilot", able on demand to replace the human operator, has been implemented on an embedded control board. This cyber-pilot overrides the commands thanks to a custom hardware signal mixer. The drone is able to localize itself in the environment without ground assistance by using a camera possibly mounted on a 3 Degrees Of Freedom (DOF) gimbal suspension. A computer vision system elaborates the video stream pointing out land markers with known absolute position and orientation. This information is fused with accelerations from a 6-DOF Inertial Measurement Unit (IMU) to generate a "virtual sensor" which provides refined estimates of the pose, the absolute position, the speed and the angular velocities of the drone. Due to the importance of this sensor, several fusion strategies have been investigated. The resulting data are, finally, fed to a control algorithm featuring a number of uncoupled digital PID controllers which work to bring to zero the displacement from the desired trajectory.

10.
J Nanobiotechnology ; 18(1): 147, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081777

RESUMO

BACKGROUND: The mechanical properties of single living cells have proven to be a powerful marker of the cell physiological state. The use of nanoindentation-based single cell force spectroscopy provided a wealth of information on the elasticity of cells, which is still largely to be exploited. The simplest model to describe cell mechanics is to treat them as a homogeneous elastic material and describe it in terms of the Young's modulus. Beside its simplicity, this approach proved to be extremely informative, allowing to assess the potential of this physical indicator towards high throughput phenotyping in diagnostic and prognostic applications. RESULTS: Here we propose an extension of this analysis to explicitly account for the properties of the actin cortex. We present a method, the Elasticity Spectra, to calculate the apparent stiffness of the cell as a function of the indentation depth and we suggest a simple phenomenological approach to measure the thickness and stiffness of the actin cortex, in addition to the standard Young's modulus. CONCLUSIONS: The Elasticity Spectra approach is tested and validated on a set of cells treated with cytoskeleton-affecting drugs, showing the potential to extend the current representation of cell mechanics, without introducing a detailed and complex description of the intracellular structure.


Assuntos
Actinas/química , Análise de Célula Única/métodos , Citoesqueleto de Actina/metabolismo , Encéfalo , Linhagem Celular , Módulo de Elasticidade , Elasticidade , Humanos , Cinética , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Modelos Biológicos , Nanotecnologia , Análise Espectral , Estresse Mecânico
11.
BMC Cancer ; 19(1): 283, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922323

RESUMO

BACKGROUND: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. METHODS: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. DISCUSSION: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. TRIAL REGISTRATION: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Junção Esofagogástrica/patologia , Paclitaxel/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Junção Esofagogástrica/metabolismo , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida/psicologia , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/psicologia , Resultado do Tratamento , Ramucirumab
12.
Eur Radiol ; 29(3): 1285-1292, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30171360

RESUMO

OBJECTIVES: To date, there is no approved second-line treatment for patients dismissing sorafenib or ineligible for this treatment, so it would be useful to find an effective alternative treatment option. The aim of our study was to evaluate safety, feasibility and effectiveness of transarterial chemoembolisation with degradable starch microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (sorafenib) due to unbearable side effects or clinical contraindications. METHODS: Forty consecutive BCLC stage B or C patients (31 male; age, 70.6 ± 13.6 years), with intermediate or locally advanced HCC dismissing or ineligible for sorafenib administration, who underwent DSM-TACE treatment cycle via lobar approach were prospectively enrolled. Tumour response was evaluated on multidetector computed tomography based on mRECIST criteria. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At 1-year follow-up, ODC of 52.5% was registered. PFS was 6.4 months with a median OS of 11.3 months. CONCLUSIONS: DSM-TACE is safe and effective as a second-line treatment in HCC patients dismissing or ineligible for sorafenib. KEY POINTS: • DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Amido/farmacologia , Idoso , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Microesferas , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Future Oncol ; 15(20): 2349-2360, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28440086

RESUMO

Aim: This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. Patients & methods: Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice-daily on days 1-14 every 3 weeks. Results: Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. Conclusion: DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Irinotecano/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Esquema de Medicação , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Microesferas , Pessoa de Meia-Idade , Intervalo Livre de Progressão
14.
Curr Treat Options Oncol ; 20(3): 23, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30790063

RESUMO

OPINION STATEMENT: Unresectable or relapsed malignant pleural mesothelioma (MPM) has dismal prognosis. First-line combination therapy with pemetrexed and a platinum analog allows a modest survival benefit, while no clear therapeutic options exist for the second-line therapy. In this setting, pemetrexed seems to be the most active drug; however, the inclusion in front-line treatment limits its use in further lines. Nevertheless, rechallenge with one or both drugs used in first-line remains a feasible strategy for responder patients. Alternatively, only few cytotoxic drugs have demonstrated a mild activity in refractory MPM. Among other options, targeted therapy has unfortunately produced disappointing results as salvage treatment probably due to the lack of a clear understanding of the tumor biology. In contrast, recent data suggest moderate efficacy and mild toxicity of immunotherapy also for the treatment of MPM. The combination of checkpoint inhibitors with chemotherapy or other immunological agents seems promising and could really "raise the bar" in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Terapia de Alvo Molecular , Neoplasias Pleurais/tratamento farmacológico , Antineoplásicos , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelioma Maligno , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Prognóstico , Resultado do Tratamento
15.
J Oral Maxillofac Surg ; 77(3): 463-470, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30347201

RESUMO

PURPOSE: The purpose of this study was to measure the frequency of bleeding during and after tooth extraction in patients exposed to direct oral anticoagulants (DOACs) and identify risk factors for prolonged or excessive bleeding. MATERIALS AND METHODS: This retrospective cohort study involved 100 patients who underwent tooth extractions according to the European Heart Rhythm Association protocol: continuation of DOAC therapy for extractions of up to 3 teeth in the same session performed at the (presumed) time of DOAC trough concentration. We respected an interval of at least 4 hours between extraction and last DOAC intake. The outcome of interest was incidence of mild, moderate, and severe bleeding during the intervention and in the 7-day follow-up period. Data analysis considered the presence of comorbidities as the primary predictor for bleeding; additional predictors were age, gender, type of comorbidity, indication for DOAC therapy, DOAC agent, and extraction of contiguous teeth. RESULTS: Of the patients, 64 had comorbidities (diabetes in 50%). The distributions of demographic, clinical, and dental variables were similar for patients with and without comorbidities. We observed 4 bleeding episodes (1 moderate episode 1 hour after the extraction and 3 mild episodes the day after the extraction) in the comorbidity group and none in the non-comorbidity group (4 of 64 vs 0 of 36, P = .29; overall bleeding rate, 4 of 100). The factor significantly triggering bleeding in patients with comorbidity was extractions of couples and triplets of multirooted teeth (P = .004). CONCLUSIONS: Tooth extractions in patients with comorbidities taking DOACs may be safely managed as long as they are performed at least 4 hours after the last DOAC intake and do not involve 2 or 3 contiguous premolars and molars.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia/tratamento farmacológico , Extração Dentária , Administração Oral , Comorbidade , Humanos , Estudos Retrospectivos
16.
J Neurophysiol ; 119(3): 849-861, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29167328

RESUMO

Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise from either too little or too much dopamine (DA). Akinesia stems from DA neuronal cell loss, and dyskinesia often stems from an overdose of DA medication. Cognitive behaviors typically associated with frontal cortical function, such as working memory and task switching, are also affected by too little or too much DA in PD. Whether motor and cognitive circuits overlap in PD is unknown. In this article, we show that whereas motor performance improves in people with PD when on dopaminergic medication compared with off medication, perceptual decision-making based on previously learned information (priors) remains impaired whether on or off medications. To rule out effects of long-term DA treatment and dopaminergic neuronal loss such as occur in PD, we also tested a group of people with dopa-unresponsive focal dystonia, a disease that involves the basal ganglia, like PD, but has motor symptoms that are insensitive to dopamine treatment and is not thought to involve frontal cortical DA circuits, unlike PD. We found that people with focal dystonia showed intact perceptual decision-making performance but impaired use of priors in perceptual decision-making, similar to people with PD. Together, the results show a dissociation between motor and cognitive performance in people with PD and reveal a novel cognitive impairment, independent of sensory and motor impairment, in people with focal dystonia. The combined results from people with PD and people with focal dystonia provide mechanistic insights into the role of basal ganglia non-dopaminergic circuits in perceptual decision-making based on priors.


Assuntos
Tomada de Decisões/fisiologia , Dopamina/fisiologia , Aprendizagem/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Percepção Visual/fisiologia , Discriminação Psicológica/fisiologia , Distúrbios Distônicos/fisiopatologia , Distúrbios Distônicos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Neurophysiol ; 120(5): 2614-2629, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30183470

RESUMO

Recent findings indicate that monkeys can report their confidence in perceptual decisions and that this information is encoded in neurons involved in making decisions, including the lateral intraparietal area (LIP) and the supplementary eye field (SEF). A key issue to consider when studying confidence is that decision accuracy often correlates with confidence reports; when we are performing well, we generally feel more confident. Expanding on work performed in humans, we designed a novel task for monkeys that dissociates perceptual information leading to decisions from perceptual information leading to confidence reports. Using this task, we recently showed that decoded ensemble activity recorded from the superior colliculus (SC) reflected decisions rather than confidence reports. However, our previous population level analysis collapsed over multiple SC neuronal types and therefore left open the possibility that first, individual discharge rates might encode information related to decision confidence, and second, different neuronal cell types within the SC might signal decision confidence independently of decision accuracy. We found that when decision accuracy and decision confidence covaried, modulation occurred primarily in neurons with prelude activity (buildup neurons). However, isolating decision confidence from decision accuracy uncovered that only a few, primarily buildup neurons showed signals correlating uniquely with decision confidence and the effect sizes were very small. Based on this work and our previous work using decoding methods, we conclude that neuronal signals for decision confidence, independent of decision accuracy, are unlikely to exist at the level of single or populations of neurons in the SC. Our results together with other recent work call into question normative models of confidence based on the optimal readout of decision signals. NEW & NOTEWORTHY Models of decision confidence suggest that our sense of confidence is an optimal readout of perceptual decision signals. Here, we report that a subcortical area, the superior colliculus (SC), contains neurons with activity that signal decisions and confidence in a task in which decision accuracy and confidence covary, similar to area lateral intraparietal area in cortex. The signals from SC occur primarily in the neurons with prelude activity (buildup neurons). However, in a task that dissociates decision accuracy from decision confidence, we find that only a few individual neurons express unique signals of confidence. These results call into question normative models of confidence based on optimal readout of perceptual decision signals.


Assuntos
Tomada de Decisões , Neurônios/fisiologia , Colículos Superiores/fisiologia , Animais , Macaca mulatta , Masculino , Percepção , Colículos Superiores/citologia
18.
Future Oncol ; 14(10): 919-926, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29528255

RESUMO

AIM: To evaluate gefitinib outcomes in EGFR-mutated non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, according to their sarcopenia status. PATIENTS & METHODS: We retrospectively evaluated 33 patients with advanced NSCLC and EGFR mutations (exon 19 or 21), dividing them into sarcopenic patients, with low skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men, and nonsarcopenic patients. RESULTS: Sarcopenia does not affect response to gefitinib treatment in EGFR mutated NSCLC patients, even if it is a bad prognostic indicator for overall survival (p = 0.035). CONCLUSION: Early recognition of sarcopenia is beneficial for prevention of cancer cachexia and detection of patients at potential risk of serious adverse events. Gefitinib dosage should be reduced and modulated in sarcopenic patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Quinazolinas/uso terapêutico , Sarcopenia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Caquexia/prevenção & controle , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Relação Dose-Resposta a Droga , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Sarcopenia/tratamento farmacológico , Sarcopenia/mortalidade , Análise de Sobrevida , Resultado do Tratamento
19.
J Vasc Interv Radiol ; 28(9): 1234-1239, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28757286

RESUMO

PURPOSE: To compare transfemoral approach (TFA) and transradial approach (TRA) in patients undergoing hepatic chemoembolization in terms of safety, feasibility, and procedural variables, including fluoroscopy time, radiation dose (reference air kerma [RAK]), and patient preference. MATERIALS AND METHODS: A single-center prospective intrapatient comparative study was conducted with 42 consecutive patients with hepatic malignancies who received 2 consecutive treatment sessions of unilobar hepatic chemoembolization within a 4-week interval over a 6-month period with both TRA and TFA. All procedures were performed by 1 interventional radiologist who assessed the eligibility of patients for inclusion in the study. The primary endpoint was intraprocedural conversion rate. Secondary endpoints were access site complications, angiographic and procedural variables, and evaluation of patient discomfort and preferences. RESULTS: A 100% technical success rate and a crossover rate of 0% were recorded. There were no major vascular complications and similar rates of minor complications (4.8% for TRA, 7.1% for TFA; P = .095), which were self-limited and without any clinical sequelae. TRA treatments required a significantly longer preparation time for the procedure (P = .008) with no significant differences for other procedural variables. Greater discomfort at the access route and patient inability to perform basic activities after the procedure were recorded for TFA (P < .001). TRA was preferred by 35 patients (35/42) for potential future transarterial procedures. CONCLUSIONS: TRA is safe and feasible for transarterial hepatic chemoembolization, with high technical success, low overall complications, and improved patient comfort.


Assuntos
Quimioembolização Terapêutica , Artéria Femoral , Neoplasias Hepáticas/terapia , Artéria Radial , Idoso , Estudos de Viabilidade , Feminino , Fluoroscopia , Humanos , Masculino , Medição da Dor , Estudos Prospectivos , Punções , Doses de Radiação , Radiografia Intervencionista , Resultado do Tratamento
20.
J Neurophysiol ; 116(1): 191-200, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27075543

RESUMO

The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na(+) current that either persists or resurges following Na(+) channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making.


Assuntos
Potenciais da Membrana/fisiologia , Neurônios/fisiologia , Sódio/metabolismo , Colículos Superiores/fisiologia , Animais , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos Sprague-Dawley , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/metabolismo , Colículos Superiores/efeitos dos fármacos , Técnicas de Cultura de Tecidos , Imagens com Corantes Sensíveis à Voltagem
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