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1.
Artigo em Inglês | MEDLINE | ID: mdl-39180353

RESUMO

Computed tomography is commonly used to evaluate the reptile coelom. One challenge in the acquisition of contrast-enhanced CT studies in reptiles is the difficulty in placing intravenous catheters due to the poor conspicuity of peripheral vessels. To overcome these limitations, intraosseous catheterization of the long bones (humerus, femur, and tibia) can be used. The purpose of this prospective study was to assess the feasibility and diagnostic value of contrast-enhanced CT of the coelom using a femoral intraosseous route for contrast administration. Twelve healthy juvenile green iguanas were enrolled. In 9 of 12 iguanas, vascular phases were obtained, providing strong, homogeneous enhancement of the arterial and venous tree concurrently. In these nine cases, Phase #1, acquired 60 s after beginning the injection of contrast medium, provided maximal contrast between the hepatic parenchyma and hepatic vasculature. In the remaining three cases, injection failure resulted from intracortical placement of the catheter tip. Histological examination of the liver, kidneys, and femur was performed to determine the pathomorphological correlates of the CT findings; in a third of patients, some degree of contrast-induced renal toxicity was documented, which in mammalians shows potential for reversibility. Four iguanas had iatrogenic structural damage to the femoral growth plates attributed to intraosseous catheter placement. A femoral intraosseous route can be used in green iguanas for iodinated contrast medium administration for CT angiography. For the greatest contrast between coelomic organs and vascular structures, at least one postcontrast acquisition 60 s after initiation of contrast administration is recommended when using this technique.

2.
Alzheimers Dement ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39072908

RESUMO

INTRODUCTION: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. DISCUSSION: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. HIGHLIGHTS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations  Cases had corticospinal tract microgliosis and severe Aß pathology in motor cortex  There was no evidence of amyloid deposition in the spinal cord white matter  All the neuropathology images are available for online visualization  Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.

3.
Daru ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888730

RESUMO

BACKGROUND: The analysis of how people search and "navigate" the internet to obtain health-related information and how they communicate and share this information can provide valuable knowledge about the disease patterns behaviour and health habits of populations. OBJECTIVE: To determine the population's interest in drug-related problems through information search trends. METHOD: A descriptive ecological correlational study, based on obtaining Google Trends data. VARIABLES STUDIED: relative search volume (RSV), evolution over time, milestones and seasonality. RESULTS: The most searched topic was drug overdose, with mean RSV of 56.25 ± 0.65. The highest increase occurred in the contraindication topic (R2 = 0.87, p < 0.001). The main milestone was observed in the drug overdose topic in July 2018 (RSV = 100). A very close relationship was found between adverse drug reaction and contraindication (R = 0.89, p < 0.001). Slight seasonality was noted in the adverse drug reaction (augmented Dickey-Fuller test [ADF] = -1.96), contraindication (ADF = -2.66) and drug interaction (ADF = -1.67) topics, but did not show an epidemiological trend. CONCLUSIONS: The greatest public interest was found in the drug overdose and contraindication topics, which showed a stronger upward trend, although the seasonality study did not show any very notable data or demonstrate epidemiological information search behaviour. The main milestone observed was due to media factors related to the consumption of narcotics. There was a clear difference in English-speaking countries in the use of the drug overdose topic. A correlation between the adverse drug reaction and contraindication topics was confirmed.

4.
J Vasc Access ; : 11297298231220537, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38205609

RESUMO

BACKGROUND: Creating Vascular Access Teams (VAT) provides an expert nursing role that contributes to the training and continuous improvement of healthcare personnel. They can offer greater clinical safety, reducing complications and costs. Peripherally inserted central catheters (PICCs) and midline catheters (ML) can be safe and cost-effective alternatives to other types of venous access (VA). The aim of the study was to analyse our centre's VAT first 12 months of activity. The primary outcome was reported complications. Secondary outcomes were cause of catheter removal, consultancy activity and economic impact of VAT implantation. METHODOLOGY: A longitudinal, descriptive study was carried out from March 2019 to March 2020. Using consecutive sampling, all VA inserted, and all consults received were included. Patients under 18 years of age were excluded. RESULTS: The VAT inserted 1257 catheters into 1056 patients (291 MLs, 966 PICCs). The mean dwell time was 14.9 days for MLs and 59.07 days for PICCs. The main reason for removing VA was end of treatment (80.7%). During VA follow-up confirmed infection was detected in 1 ML (0.3%) and nine PICCs (0.9%). Symptomatic thrombosis was reported in 2 MLs (0.7%) and 16 PICCs (1.7%). The VAT received 367 consultations, and the main reason for consultation was to resolve doubts regarding the management of VA (80.9%). The insertion of ML and PICC catheters represented annual estimated economic savings of €867,688.44€. CONCLUSIONS: Our study provides a detailed analysis of VAT's activity, its relevance to clinical safety, and to efficient resource management within our hospital. It demonstrates how VAT establishment can be a safe and efficient intervention that enhances care quality.

5.
Nature ; 623(7985): 157-166, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853118

RESUMO

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).


Assuntos
Neoplasias Encefálicas , Glioblastoma , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Nestina/genética , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Vírus Oncolíticos/fisiologia , Reprodutibilidade dos Testes , Análise de Sobrevida , Linfócitos T/citologia , Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral/imunologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/fisiologia
6.
Av. psicol. latinoam ; 41(3): [1-16], 20230905.
Artigo em Espanhol | LILACS | ID: biblio-1512780

RESUMO

El propósito de la investigación fue desarrollar una escala para medir el proceso de ajuste a la vida universitaria. Este constructo multifactorial se basa en un modelo teórico de tres dimensiones: académica, social e institucional. La muestra principal estuvo conformada por 673 estudiantes: 42.1 % mujeres, 57.7 % hombres y 0.3 % otro, con un promedio de 18.29 años. En el primer análisis se encontraron evidencias asociadas al contenido de las dimensiones de la escala denominada AjusteU. En el análisis de validez convergente se halló una correlación de 0.582 a un nivel de significancia del 0.01 (bilateral) con el instrumento CAVU, otra medida del ajuste a la vida universitaria. En el tercer análisis se validó el planteamiento teórico con los datos empíricos mediante un modelo de ecuaciones estructurales. Finalmente, en el análisis predictivo se comprobó que la puntuación de la escala AjusteU se asoció significativamente con el rendimiento del primer período universitario. Se concluye que estas evidencias empíricas permiten un uso adecuado de los resultados, especialmente en la toma de decisiones oportunas para favorecer el proceso de transición de secundaria a la educación superior. La principal limitación fue la aplicación de la escala en modalidad remota en el contexto de pandemia, por lo que las experiencias del estudiantado podrían ser diferentes en un entorno presencial


The purpose of the research was to develop a scale to measure college adjustment. The theorical model was based on three dimensions: academical, social and institutional. The principal sample was conformed for 673 students: 42.1 % women, 57.7 % men and 0.3 % other, with an average of 18.29 years old. In the first analysis were found evidence associated to the content of the dimensions of the scale denominated AjusteU. In the validity convergent analysis was found a correlation of 0.582 to a significance level of 0.01 (bilateral) with the instrument CAVU, other measure that is related to the adjustment process. In the third analysis, the theoretical approach was validated with empirical data using a structural equation model. Finally, in the predictive analysis was proved that the scoring of the scale AjusteU was associated significantly with the performance of the first period of college. The conclusion is that this empirical evidence allows an appropriate use of their results, specifically in the opportune decision making to favor the transition process from high school to higher education. The main limitation was the application of the scale in the remote modality in the pandemic context, therefore the experiences of the students might be different in an on-site experience.


O objetivo da pesquisa foi desenvolver uma escala para medir o processo de adaptação à vida universitária. Este construto multifatorial é baseado em um modelo teórico de três dimensões: acadêmica, social e institucional. A amostra principal foi composta por 673 estudantes, sendo: 42.1 % mulheres, 57.7 % homens e 0.3 % outros, com idade média de 18.29 anos. Na primeira análise, foram encontradas evidências associadas ao conteúdo das dimensões da escala denominada AjusteU. Na análise de validade convergente, uma correlação de 0.582 foi encontrada em um nível de significância de 0.01 (bilateral) com o instrumento CAVU, outra medida de adaptação à vida universitária. Na terceira análise, a abordagem teórica foi validada com dados empíricos usando um modelo de equações estruturais. Por fim, na análise preditiva verificouse que a pontuação da escala AjusteU esteve significativamente associada ao desempenho do primeiro período universitário. Concluise que estas evidências empíricas permitem uma utilização adequada dos resultados, sobretudo na tomada de decisões oportunas que favoreçam o processo de transição do ensino médio para o superior. A principal limitação do estudo foi a aplicação da escala de forma remota no contexto de pandemia, de modo que as experiências do corpo discente poderiam ser diferentes em um ambiente presencial.


Assuntos
Humanos
7.
Cells ; 12(16)2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37626875

RESUMO

Degranulation mediated killing mechanism by NK cells is dependent on store-operated Ca2+ entry (SOCE) and has optimum at moderate intracellular Ca2+ elevations so that partial block of SOCE optimizes the killing process. In this study, we tested the effect of the selective blocker of KCa3.1 channel NS6180 on SOCE and the killing efficiency of NK cells from healthy donors and NK-92 cells against T-ALL cell line Jurkat. Patch-clamp analysis showed that only one-quarter of resting NK cells functionally express KCa3.1 current, which increases 3-fold after activation by interleukins 15 and 2. Nevertheless, blockage of KCa3.1 significantly reduced SOCE and intracellular Ca2+ rise induced by IL-15 or target cell recognition. NS6180 (1 µM) decreased NK degranulation at zero time of coculture with Jurkat cells but already after 1 h, the degranulation reached the same level as in the control. Monitoring of target cell death by flow cytometry and confocal microscopy demonstrated that NS6180 significantly improved the killing ability of NK cells after 1 h in coculture with Jurkat cells and increased the Jurkat cell fraction with apoptotic and necrotic markers. Our data evidence a strong dependence of SOCE on KCa3.1 activity in NK cells and that KCa3.1 specific block can improve NK cytotoxicity.


Assuntos
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Tiazinas , Humanos , Células Jurkat , Células Matadoras Naturais
8.
Res Social Adm Pharm ; 19(11): 1440-1445, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37481351

RESUMO

BACKGROUND: For years, there has been controversy about the meaning of medication-related problems (MRPs). This has led several authors to attempt to redefine and classify this term with the aim of using it correctly in the healthcare setting. So far without achieving the desired objective, resulting in erroneous results in the sources of information and thus in malpractice in the sector. OBJECTIVE: To describe and analyze the appropriateness of the existing indexing of scientific publications in the MEDLINE bibliographical database with respect to drug-related problems (DRPs) and to determine whether the descriptors used fulfilled the function of suitably representing this concept. METHODS: A descriptive study was conducted, using the following search terms: Medication Errors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Contraindications, Drug. The sample size was calculated by estimating population parameters in an infinite population (expected value = 0.05; precision of interval = 0.05; level of confidence = 0.95) and the selection method was simple random sampling without replacement, taking the total number of bibliographical references in the database as the basis. The agreement of the indexing with DRPs was evaluated with the coefficient of determination (R2), and the Cohen kappa coefficient was used for the association between the definition of the descriptors and the objective of the article. RESULTS: The 1930 records analyzed showed a total of 2888 different major topics. These major topics were present, with at least one of the five descriptors studied, in 482 (25.0%; 95% CI 23.0-27.0) documentary files, with statistically significant differences between the two phases analyzed (χ2 = 183.8; degrees of freedom (df) = 1; p < 0.001): 1st phase, 295 (13.3%; 95% CI 13.7-16.9) and 2nd phase, 187 (9.7%; 95% CI 8.4-11.0). Overall scientific output with the five descriptors showed a coefficient of determination (R2) of 0.9 (p < 0.001) and the relationship between the objective of the study and the definitions of the five descriptors was 0.9 (p < 0.001). CONCLUSIONS: There was a very good direct exponential trend of the overall scientific output retrieved with the terms associated with DRPs, although the progression of the five descriptors separately did not show a growth model conforming to expectations. There was a moderate agreement between the objective of the study and the definition of each of the five descriptors used and a low relationship between the objective of the study and the concept of DRPs used for this investigation. It is essential to have a descriptor that unifies the terminological diffusion that has existed up till now, since process (causes) and effects (outcomes) have been mixed together under the various definitions and classifications of DRPs found in the studies.


Assuntos
Overdose de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , MEDLINE , Bases de Dados Bibliográficas , Bases de Dados Factuais
9.
J Zoo Wildl Med ; 54(2): 326-331, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37428695

RESUMO

General anesthesia is often required in elasmobranch species for medical procedures. A variety of anesthetic drugs have been administered to elasmobranchs with wide variability in efficacy and safety. A retrospective review of 47 anesthetic procedures using IV propofol in eight different elasmobranch species at the Georgia Aquarium from 2010 to 2022 was performed. Cases involving seven sand tiger sharks (Carcharias taurus), four largetooth sawfish (Pristis perotteti), one longcomb sawfish (Pristis zijsron), four blacktip reef sharks (Carcharhinus melanopterus), three silvertip sharks (Carcharhinus albimarginatus), one sandbar shark (Carcharhinus plumbeus), five cownose rays (Rhinoptera bonasus), and one blotched fantail stingray (Taeniura meyeni) were evaluated. Induction dose of IV propofol (median: 2.5; 25-75%: 2.3-3.0; range: 1.7-4.0 mg/kg), time to desired effect (median: 4.0; 25-75%: 2.0-5.0; range: 0.5-15.0 min) and anesthetic duration (median: 76.0; 25-75%: 61.5-119.0; range: 27-216 min) were reported in all species. In six procedures (12.7%), maintenance of desired anesthetic plane required a supplemental dose of propofol IV (1 mg/kg) or addition of tricaine methanesulfonate (70 mg/L) as an immersion bath. The most common side effects were apnea and prolonged recovery. The IV propofol was efficacious and provided a procedural plane of anesthesia for a clinically relevant period of time in the majority of elasmobranch species, but observation for and management of complications is warranted.


Assuntos
Anestesia , Anestésicos , Propofol , Tubarões , Rajidae , Animais , Georgia , Estudos Retrospectivos , Anestesia/veterinária
10.
MedUNAB ; 26(1): 9-11, 20230731.
Artigo em Inglês | LILACS | ID: biblio-1525482

RESUMO

A key global health objective is to promote the advancement of scientific production in disciplines with low publication volume, as opposed to specialties addressing pathologies that represent the greatest global disease burden (1). Dermatology is one such discipline, which has experienced substantial growth in research on immunopathogenic, pathophysiological, diagnostic, and therapeutic aspects (2-4). The extent to which Latin American authors and institutions have been involved in publishing scientific articles in the dermatology journals with highest impact worldwide remains unknown.


Un objetivo clave de salud mundial es promover el avance de la producción científica en disciplinas con bajo volumen de publicación, a diferencia de especialidades que abordan las patologías que representan la mayor carga de enfermedad a nivel mundial (1). La Dermatología es una de esas disciplinas que ha experimentado un crecimiento sustancial en investigación en aspectos inmunopatogénicos, fisiopatológicos, diagnósticos y terapéuticos (2-4). El alcance en el cual los autores e instituciones latinoamericanas han participado en la publicación de artículos científicos en revistas de dermatología con mayor impacto mundial permanece incierto.


Um objetivo fundamental da saúde global é promover o avanço da produção científica em disciplinas com baixo volume de publicações, em oposição às especialidades que abordam patologias que representam a maior carga de doenças em todo o mundo (1). A Dermatologia é uma das disciplinas que tem experimentado um crescimento substancial nas pesquisas em aspectos imunopatogênicos, fisiopatológicos, diagnósticos e terapêuticos (2-4). A extensão da participação de autores e instituições latino-americanas na publicação de artigos científicos em revistas de dermatologia de maior impacto global permanece incerta.


Assuntos
Dermatologia , Hispânico ou Latino , Bibliometria , Autoria na Publicação Científica , Comunicação Acadêmica
13.
J Clin Med ; 11(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36431351

RESUMO

(1) Background: One possible way to investigate the potential impact or susceptibility of buckling on different manual techniques is to measure compressive loads during canal negotiation. The higher their values, the easier and quicker the critical load level to buckling is reached, leading to possible instrument lateral deformation. The objective of the present study was to investigate the impacts of compressive loads on a small K-file manipulated with different techniques for canal negotiation in simulated narrow and curved canals. (2) Methods: The tooth model selected was a plastic double-curved premolar 23 mm long (DRSK Group AB, Kasernvagen 2, SE-281 35, Hassleholm, Sweden) with an extremely narrow canal lumen to mimic a very difficult anatomical scenario. An experienced endodontist performed the negotiation of 90 of these artificial teeth randomly assigned to 3 different groups of 30 blocks each, respectively, using 3 different techniques: Group A: watch winding/pull (WW) motion; Group B: balanced forces (BF) technique; Group C: envelope of motion (EOM). The measurement system was based on the use of a dynamometer, Instron, Ltd. (model 2525-818 2kN f.s.), linked to a data acquisition unit HBM MGC+ to test all the compression and tensile loads, including all the peaks. (3) Results: All data acquired were processed by the CATMAN AP HBM software. Multiple comparisons for the highest compressive loads estimated the mean difference between WW vs. BF techniques of 3.60 [95% confidence interval (CI): 2.85 to 4.35, p < 0.001], WW vs. EOM of −1.76 (95% CI: −2.11 to 1.40, p < 0.001), and BF vs. EOM −5.36 (95% CI: −6.04 to −4.67, p < 0.001). (4) Conclusions: In conclusion, among the tested manual motions, the BF technique (Group B) was the most susceptible to buckling with the highest compressive load. WW motion (Group A) and EOM (Group C) were less susceptible to buckling than the BF technique. Therefore, a pressure-free manipulation of manual files, such as WW motion or EOM, can help reduce the susceptibility to buckling during the negotiation of narrow-curved canals.

14.
Mol Ther Oncolytics ; 26: 275-288, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36032633

RESUMO

CAN-2409 is a replication-deficient adenovirus encoding herpes simplex virus (HSV) thymidine kinase (tk) currently in clinical trials for treatment of glioblastoma. The expression of tk in transduced cancer cells results in conversion of the pro-drug ganciclovir into a toxic metabolite causing DNA damage, inducing immunogenic cell death and immune activation. We hypothesize that CAN-2409 combined with DNA-damage-response inhibitors could amplify tumor cell death, resulting in an improved response. We investigated the effects of ATR inhibitor AZD6738 in combination with CAN-2409 in vitro using cytotoxicity, cytokine, and fluorescence-activated cell sorting (FACS) assays in glioma cell lines and in vivo with an orthotopic syngeneic murine glioma model. Tumor immune infiltrates were analyzed by cytometry by time of flight (CyTOF). In vitro, we observed a significant increase in the DNA-damage marker γH2AX and decreased expression of PD-L1, pro-tumorigenic cytokines (interleukin-1ß [IL-1ß], IL-4), and ligand NKG2D after combination treatment compared with monotherapy or control. In vivo, long-term survival was increased after combination treatment (66.7%) compared with CAN-2409 (50%) and control. In a tumor re-challenge, long-term immunity after combination treatment was not improved. Our results suggest that ATR inhibition could amplify CAN-2409's efficacy in glioblastoma through increased DNA damage while having complex immunological ramifications, warranting further studies to determine the ideal conditions for maximized therapeutic benefit.

17.
Ann Med Surg (Lond) ; 74: 103280, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35127067

RESUMO

Scientific research plays a fundamental role in current medical practice and it is of great importance that medical students relate to it from the beginning of their professional career, since it generates multiple benefits that will be reflected during the course of their careers as university students and future professionals. However, getting involved in research during the undergraduate years is not always easy, as there are different obstacles and challenges that result in a reduced number of research students. Because of this, it is necessary to adopt appropriate strategies and measures to help facilitate this process, in order to foster the early development of essential skills that will facilitate responsible clinical practice. Knowing the evidence on this issue is fundamental to propose educational solutions depending on each context.

18.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35017150

RESUMO

BACKGROUND: Intratumoral viral oncolytic immunotherapy is a promising new approach for the treatment of a variety of solid cancers. CAN-2409 is a replication-deficient adenovirus that delivers herpes simplex virus thymidine kinase to cancer cells, resulting in local conversion of ganciclovir or valacyclovir into a toxic metabolite. This leads to highly immunogenic cell death, followed by a local immune response against a variety of cancer neoantigens and, next, a systemic immune response against the injected tumor and uninjected distant metastases. CAN-2409 treatment has shown promising results in clinical studies in glioblastoma (GBM). Patients with GBM are usually given the corticosteroid dexamethasone to manage edema. Previous work has suggested that concurrent dexamethasone therapy may have a negative effect in patients treated with immune checkpoint inhibitors in patients with GBM. However, the effects of dexamethasone on the efficacy of CAN-2409 treatment have not been explored. METHODS: In vitro experiments included cell viability and neurosphere T-cell killing assays. Effects of dexamethasone on CAN-2409 in vivo were examined using a syngeneic murine GBM model; survival was assessed according to Kaplan-Meier; analyses of tumor-infiltrating lymphocytes were performed with mass cytometry (CyTOF - cytometry by time-of-flight). Data were analyzed using a general linear model, with one-way analysis of variance followed by Dunnett's multiple comparison test, Kruskal-Wallis test, Dunn's multiple comparison test or statistical significance analysis of microarrays. RESULTS: In a mouse model of GBM, we found that high doses of dexamethasone combined with CAN-2409 led to significantly reduced median survival (29.0 days) compared with CAN-2409 treatment alone (39.5 days). CyTOF analyses of tumor-infiltrating immune cells demonstrated potent immune stimulation induced by CAN-2409 treatment. These effects were diminished when high-dose dexamethasone was used. Functional immune cell characterization suggested increased immune cell exhaustion and tumor promoting profiles after dexamethasone treatment. CONCLUSION: Our data suggest that concurrent high-dose dexamethasone treatment may impair the efficacy of oncolytic viral immunotherapy of GBM, supporting the notion that dexamethasone use should be balanced between symptom control and impact on the therapeutic outcome.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Dexametasona/uso terapêutico , Glioblastoma/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunoterapia/métodos , Terapia Viral Oncolítica/métodos , Animais , Neoplasias Encefálicas/patologia , Dexametasona/farmacologia , Feminino , Glioblastoma/patologia , Glucocorticoides/farmacologia , Humanos , Camundongos , Microambiente Tumoral
19.
J Neurosurg Sci ; 66(3): 251-257, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34763389

RESUMO

Traumatic brain injury is caused by mechanical forces impacting the skull and its internal structures and constitutes one of the main causes of morbidity and mortality in the world. Clinically, severe traumatic brain injury is associated with the development of acute lung injury and so far, few studies have evaluated the cellular, molecular and immunological mechanisms involved in this pathophysiological process. Knowing and investigating these mechanisms allows us to correlate pulmonary injury as a predictor of cerebral hypoxia in traumatic brain injury and to use this finding in decision making during clinical practice. This review aims to provide evidence on the importance of the pathophysiology of traumatic brain injury-acute lung injury, and thus confirm its role as a predictor of cerebral hypoxia, helping to establish an appropriate therapeutic strategy to improve functional outcomes and reduce mortality.


Assuntos
Lesão Pulmonar Aguda , Lesões Encefálicas Traumáticas , Hipóxia Encefálica , Lesão Pulmonar Aguda/complicações , Humanos , Hipóxia Encefálica/complicações
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