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BACKGROUND: Diagnosis of dementia with Lewy bodies (DLB) is challenging, especially in the earlier stages of the disease, owing to the clinical overlap with other neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). We aimed to identify the transcranial sonography (TCS) parameters that can help us to detect early DLB patients. METHODS: In this cross-sectional study, we prospectively recruited newly diagnosed DLB patients with less than 3 years from the onset of cognitive symptoms. For comparison purposes, we also included AD and PD patients, with a disease duration of less than 3 years, and a control group. TCS was performed to assess the substantia nigra (SN) echogenicity, the width of the third ventricle, and the frontal horns of the lateral ventricles. Subsequently, TCS images were analyzed with the medical image viewer Horos in order to quantify the intensity of the echogenicity of the SN. Univariate analysis and a logistic regression model were used to identify which variables can predict the diagnosis of DLB. RESULTS: One hundred and seven participants were included (23 DLB, 26 AD, 27 PD and 31 controls). The median age of DLB patients was 75(72-77) years, with a disease duration of 2 years. DLB and PD patients showed higher SN hyperechogenicity rates (72.73% and 81.82%, respectively) and a greater area of the SN compared to AD patients and controls (p < 0.001). DLB and AD patients had wider ventricular systems than the other study groups. The SN hyperechogenicity predicted a diagnosis of DLB with an odds ratio of 22.67 (95%CI 3.98; 129.12, p < 0.001) when compared to AD patients. Unilateral and bilateral widened frontal horns predicted diagnosis of DLB compared to PD with an odds ratio of 9.5 (95%CI 0.97; 92.83, p = 0.053) and 5.7 (95%CI 0.97; 33.6, p = 0.054), respectively. CONCLUSIONS: Echogenicity of the SN and widening of the frontal horns of lateral ventricles can predict the diagnosis of early DLB in this cohort of newly diagnosed patients, when compared to AD and PD patients. Transcranial sonography, a non-invasive tool, could be helpful for the diagnosis of DLB at its earlier stages.
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Doença por Corpos de Lewy , Substância Negra , Ultrassonografia Doppler Transcraniana , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Feminino , Masculino , Idoso , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Estudos Transversais , Ultrassonografia Doppler Transcraniana/métodos , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/patologia , Doença de Parkinson/diagnóstico por imagem , Estudos Prospectivos , Doença de Alzheimer/diagnóstico por imagem , BiomarcadoresRESUMO
BACKGROUND AND AIM: Determining suitable copper parameters for monitoring Wilson disease remains a topic of ongoing discussion. International recommendations currently rely on the combination of urinary copper excretion and nonspecific liver markers when considering therapy and time elapsed since diagnosis. The emergence of exchangeable copper (CuEX) as a novel measurement reflecting the "free copper pool" held promise as a valuable target to ensure metabolic stability during follow-up, although the validation of target ranges remains unknown. We aimed to evaluate CuEX quantification in repeated samples from 92 real-world patients with Wilson disease during a 2-year period. APPROACH: Patients were classified as "stable" if a diagnosis had been made more than 1 year before and were compliant with stable anti-copper drug and dose. Otherwise, patients were classified as "nonstable." RESULTS: Two hundred and thirteen CuEX samples were obtained per clinical practice. Overall, 57% of CuEX measurements fell below the reference "range of normality," whereas only 34% were within and 9% were above normal levels. There was no association of CuEX levels with therapy, elapsed time from diagnosis, or clinical stability, although most of the samples above normality corresponded to nonstable patients. Only 23.4% of the CuEX samples were aligned with data obtained from concomitant urinary copper excretion. CONCLUSIONS: Our findings suggest that CuEX is a suboptimal tool for assessing copper homeostasis when used alone and should be used with caution if no additional information is available. Normal reference intervals for Wilson disease-treated patients should be redefined, as most CuEX quantifications fell in the lower range, with no sign of overtreatment in these patients.
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BACKGROUND: Optimal reversal agent for direct oral anticoagulant (DOAC)-associated major bleeding has not been described. Before the approval of andexanet alfa (AA) in 2018, 4-factor prothrombin complex concentrate (4F-PCC) was recommended by major guidelines. Currently, AA is recommended as the first-line agent by most guidelines. With a paucity of literature comparing the 2 agents, there is clinical value in assessing hemostatic efficacy and safety of the 2 agents. OBJECTIVE: This study aimed to evaluate hemostatic efficacy and safety of AA and 4F-PCC in all DOAC-associated major bleedings. METHODS: A multicenter, retrospective chart review was performed of adult subjects who were admitted for a DOAC-associated major bleeding and received 4F-PCC from February 2018 to May 2019 or AA from May 2019 to September 2021. Some of the exclusion criteria included not receiving a DOAC, receiving multiple reversal agents during the same hospitalization, receiving reversal for any nonmajor bleeding indication, and not receiving the full dose of a reversal agent. The primary outcome was hemostatic efficacy 24 hours after the end of the reversal agent administration. Secondary outcomes included time to administration, hospital mortality, length of stay, need for surgery, and need for additional blood product. Safety outcome was incidence of thrombotic events. RESULTS: There were 99 subjects included in the 4F-PCC group and 84 subjects in the AA group. Hemostatic efficacy was achieved in 69 subjects (69.7%) in the 4F-PCC group and 63 subjects (75%) in the AA group (P = 0.927). In-hospital mortality was seen in 20 subjects (20.2%) in the 4F-PCC group and 10 subjects (11.9%) in the AA group. Thrombotic events were seen in 7 subjects (7.1%) in the 4F-PCC group and 6 subjects (7.1%) in the AA group. CONCLUSIONS: There were no significant differences in hemostatic efficacy, in-hospital mortality, and number of thrombotic events between 4F-PCC and AA.
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Fatores de Coagulação Sanguínea , Hemorragia , Proteínas Recombinantes , Humanos , Estudos Retrospectivos , Masculino , Feminino , Hemorragia/induzido quimicamente , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/uso terapêutico , Fatores de Coagulação Sanguínea/efeitos adversos , Idoso , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Mortalidade Hospitalar , Administração Oral , Protrombina/uso terapêutico , Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Hemostáticos/administração & dosagem , Resultado do Tratamento , Fator XaRESUMO
Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this retrospective study, we analyzed a cohort of Parkinson's disease patients treated with dopamine agonists and investigated the influence of the dopamine D4 receptor gene polymorphism, DRD4 7R+, which is linked to psychiatric disorders, impulsive traits, and addictive behaviors. We found that DRD4 7R+ is a significant genetic risk factor associated with the severity of ICD.
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Transtornos Disruptivos, de Controle do Impulso e da Conduta , Agonistas de Dopamina , Doença de Parkinson , Receptores de Dopamina D4 , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Receptores de Dopamina D4/genética , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Masculino , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/administração & dosagem , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos , Polimorfismo GenéticoRESUMO
BACKGROUND AND OBJECTIVES: Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. METHODS: This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. RESULTS: The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44). CONCLUSIONS: Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.
Direct-acting antivirals (DAAs) are effective drugs for eradicating hepatitis C virus (HCV). However, concerns about the risk of cancer after HCV eradication remain. Therefore, this study aimed to compare the incidence of cancer between patients treated with anti-HCV therapies in Catalonia (Spain) and properly matched, non-HCV-infected individuals (controls).This study was based on real-world data from the public healthcare system of Catalonia, specifically from patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), or DAA only (DAA). We calculated the incidence and rate ratios of overall cancer and hepatocellular carcinoma of HCV-treated patients.We observed that the rate of overall cancer increased in patients receiving DAA or IFN+DAA, whereas the rate of hepatocellular carcinoma increased in all groups of HCV-treated patients. Of note, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis. Thus, a close monitoring for detection of cancer in patients after HCV eradication seems reasonable, especially in those with cirrhosis.
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BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.
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Conversão para Cirurgia Aberta , Obesidade , Pancreatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Idoso , Resultado do Tratamento , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Risco , Análise Multivariada , Fatores de Tempo , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Razão de Chances , Modelos Logísticos , Distribuição de Qui-Quadrado , Adulto , Laparoscopia/efeitos adversos , Perda Sanguínea Cirúrgica , Duração da Cirurgia , Europa (Continente)RESUMO
ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. In this study, we first evaluated the effect of extracellular ATP depletion with apyrase in SKOV-3, a cell line derived from metastatic ovarian carcinoma. We observed a decrease in cell migration and an increase in transepithelial electrical resistance and cell markers, suggesting a role in maintaining a mesenchymal phenotype. To identify the P2 receptor that mediated the effects of ATP, we compared the transcript levels of some P2 receptors and found that P2RX7 is three-fold higher in SKOV-3 cells than in a healthy cell line, namely HOSE6-3 (from human ovarian surface epithelium). Through bioinformatic analysis, we identified a higher expression of the P2RX7 transcript in metastatic tissues than in primary tumors; thus, P2X7 seems to be a promising effector for the malignant phenotype. Subsequently, we demonstrated the presence and functionality of the P2X7 receptor in SKOV-3 cells and showed through pharmacological approaches that its activity promotes cell migration and contributes to maintaining a mesenchymal phenotype. P2X7 activation using BzATP increased cell migration and abolished E-cadherin expression. On the other hand, a series of P2X7 receptor antagonists (A438079, BBG and OxATP) decreased cell migration. We used a CRISPR-based knock-out system directed to P2RX7. According to the results of our wound-healing assay, SKOV3-P2X7KO cells lacked receptor-mediated calcium mobilization and decreased migration. Altogether, these data let us propose that P2X7 receptor is a regulator for cancer cell migration and thus a potential drug target.
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Trifosfato de Adenosina , Movimento Celular , Neoplasias Ovarianas , Receptores Purinérgicos P2X7 , Humanos , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Feminino , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.
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Antirreumáticos , Artrite Reumatoide , Artrite Reumatoide/tratamento farmacológico , Humanos , México , Antirreumáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Feminino , Anti-Inflamatórios não Esteroides/uso terapêutico , Gravidez , Analgésicos/uso terapêuticoRESUMO
Children living in rural and migrant areas in the United States disproportionately suffer from poor oral health. Additionally, there continues to be a shortage of pediatric dentists practicing in rural/migrant areas. The purpose of this formative research study was to assess whether staff, teachers and families from rural/migrant Head Start/Early Head Start (HS/EHS) programs in California were receptive to oral health online education workshops conducted by pediatric dental residents who were assisted by bilingual (English and Spanish) community oral health workers (COHWs). Our findings suggest that partnering pediatric dental residents with bilingual COHWs to educate HS/EHS teachers, staff and parents on oral health care in rural/migrant areas could result in a rewarding experience for pediatric dentists that might lead them to practice in these communities upon graduation from their residency program. Furthermore, the positive feedback received from the teachers, staff and parents who participated in the workshops indicates they were receptive to receiving oral health information related to oral health literacy from the dental providers and COHWs. COHWs can help increase access to oral health care by serving as a bridge between families and providers by relaying information in a cultural, linguistic and sensitive manner.
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Saúde Bucal , População Rural , Migrantes , Humanos , Saúde Bucal/educação , Educação a Distância/métodos , Intervenção Educacional Precoce , Estados Unidos , California , Pré-Escolar , CriançaRESUMO
Accelerated atherosclerosis has been identified as a complication of multiple autoimmune diseases, among which Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis stands out. We describe the case of a 60-year-old patient with a history of hypertension, diabetes mellitus, and chronic kidney disease of unknown etiology, who presented two acute coronary syndromes with only a six-month difference. Rapid progression of coronary involvement was evidenced, along with increased markers of inflammatory response, usual interstitial pneumonia on tomography, and positive anti-myeloperoxidase antibodies (anti-MPO), leading to the diagnosis of microscopic polyangiitis (MPA). In these cases, timely diagnostic suspicion is crucial, as early treatment significantly impacts the course and prognosis of the disease.
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OBJECTIVE: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity. METHODS: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations. RESULTS: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF. CONCLUSION: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity.
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Antirreumáticos , Lúpus Eritematoso Sistêmico , Humanos , Hidroxicloroquina/efeitos adversos , Antirreumáticos/efeitos adversos , Estudos Transversais , Angiofluoresceinografia/métodos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Fundo de Olho , Imagem MultimodalRESUMO
A Carta de Maceió foi elaborada com base nas discussões do 3º Fórum SUS da Associação Brasileira de Alergia e Imunologia (ASBAI). O documento destaca os desafios e propostas para aprimorar a assistência a pacientes com doenças imunoalérgicas no Sistema Único de Saúde (SUS) do Brasil. Tais condições, frequentemente crônicas e debilitantes, afetam milhões de brasileiros e exigem uma abordagem integrada, desde a atenção primária à saúde até a atenção especializada. Foram discutidos a necessidade de aprimorar a gestão de referência e contrarreferência, a urgência na superação da carência de especialistas e o desafio representado pelo limitado acesso tanto a diagnóstico quanto a tratamento adequados. As doenças raras, incluindo os erros inatos da imunidade (EII), apresentam um desafio adicional, exigindo acesso a tecnologias de alto custo para diagnóstico e tratamento e cuidado multidisciplinar. Do fórum emergiram propostas como o financiamento adequado da saúde, o fortalecimento do diagnóstico precoce, a gestão integrada de cuidados, a educação continuada dos profissionais de saúde e a implementação de telemedicina. Essas ações visam um sistema de saúde mais inclusivo, eficiente e humanizado, atendendo às necessidades dos pacientes com doenças imunoalérgicas.
The Maceió Charter was based on discussions held at the 3rd Unified Health System Forum (Fórum SUS) of the Brazilian Association of Allergy and Immunology (ASBAI). This document highlights challenges and proposals to improve care for patients with immune and allergic diseases within the Brazilian Unified Health System (SUS). Such conditions, often chronic and debilitating, affect millions of Brazilians and require an integrated approach from primary health through to specialty care. The need for improved management of referrals and counter-referrals, the urgency of overcoming the shortage of specialists, and the challenge represented by limited access to proper diagnosis and treatment alike were discussed. Rare diseases, including inborn errors of immunity (IEI), pose an additional challenge, requiring access to high-cost technologies for diagnosis and treatment as well as multidisciplinary care. Several proposals emerged from the Forum, such as securing sufficient funding for health, strengthening early diagnosis, integrating management, continuing education for health professionals, and implementation of telemedicine. These proposed interventions seek a more inclusive, efficient, and humanized healthcare system which meets the needs of patients with immune and allergic diseases.
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HumanosRESUMO
Colorectal cancer is a widespread neoplasia with high ratios of chemoresistance. Phytochemicals in plant-based extracts could be useful to treat colorectal cancer, and/or reduce chemoresistance. Methanolic extract of avocado mesocarp (MEAM) has demonstrated antitumoral properties, depending on the fruit ripening stage (RS). The aim of this study was to analyze the effects of methanolic extracts of "Hass" avocado fruit at different RS on cytotoxicity, antioxidative, anti-inflammatory, anti-invasive, cell cycle, and epithelial-mesenchymal transition inhibition in colorectal adenocarcinoma cell line HT29. The MEAM showed an increasing concentration of total phenolic compounds as the RS progressed, which was correlated with antioxidant capacity measured by the Ferric Reducing Antioxidant Power assay but not with the 2.2-diphenyl-1-picrylhydrazyl assay. The specific phenolic compounds of MEAM were determined by high-performance liquid chromatography, and it was found that concentrations of epicatechin decreased while concentrations of chlorogenic acid increased as the RS progressed. The HT29 cell line was treated with MEAM for 48 h, and all MEAM had a cytotoxic effect, reported by MTT assay, nevertheless, the strongest effect was associated with the presence of chlorogenic acid. MEAM induced apoptosis and cell cycle arrest in phase G0/G1, reported by flow cytometry. Moreover, MEAM inhibited cell migration evidenced by the wound healing assay. On the other hand, MEAM significantly reduced expression of mRNA of tumor necrosis factor-alpha and cyclooxygenase 2. These effects comprise important inhibition of some hallmarks of cancer. This, in turn, may provide interesting guidelines for developing antitumoral intervention agents.
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Antineoplásicos , Neoplasias Colorretais , Persea , Humanos , Frutas/química , Antioxidantes/metabolismo , Persea/química , Metanol , Ácido Clorogênico/análise , Extratos Vegetais/química , Células HT29 , Neoplasias Colorretais/tratamento farmacológicoRESUMO
BACKGROUND: Moya moya type vasculopathy (MMV) is a rare disorder in which there is narrowing of bilateral intracranial carotid arteries (Scott and Smith in New Engl J Med 360(12):1226-1237, 2009). MECP2 duplication syndrome (MDS) is a rare genetic disorder that is caused by genetic duplications on Xq28 chromosome (Expanding the clinical picture of the MECP2 duplication syndrome. (Lim et al. in Clin Genet 91(4):557-563, 2017). Both disorders are rare and have not been described together in association. CASE PRESENTATION: Interestingly, we present a child with both MDS and MMV. Upon genetic testing, there was found to be a large, de novo duplication sequence in the patient's genome. Possible correlation between our patient's extensive genetic mutation and MMV has been evaluated. CONCLUSION: Our literature search disclosed no other known patients with both MDS and MMV. Patients with MDS should be monitored carefully for signs or symptoms of vasculopathy.
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Deficiência Intelectual Ligada ao Cromossomo X , Doença de Moyamoya , Criança , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/genética , Duplicação Gênica , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/genética , Testes GenéticosRESUMO
BACKGROUND: Optimal reversal agent for direct oral anticoagulant (DOAC)-associated major bleeding has not been described. Before the approval of andexanet alfa (AA) in 2018, 4-factor prothrombin complex concentrate (4F-PCC) was recommended by major guidelines. Currently, AA is recommended as the first-line agent by most guidelines. With a paucity of literature comparing the 2 agents, there is clinical value in assessing hemostatic efficacy and safety of the 2 agents. OBJECTIVE: This study aimed to evaluate hemostatic efficacy and safety of AA and 4F-PCC in all DOAC-associated major bleedings. METHODS: A multicenter, retrospective chart review was performed of adult subjects who were admitted for a DOAC-associated major bleeding and received 4F-PCC from February 2018 to May 2019 or AA from May 2019 to September 2021. Some of the exclusion criteria included not receiving a DOAC, receiving multiple reversal agents during the same hospitalization, receiving reversal for any nonmajor bleeding indication, and not receiving the full dose of a reversal agent. The primary outcome was hemostatic efficacy 24 hours after the end of the reversal agent administration. Secondary outcomes included time to administration, hospital mortality, length of stay, need for surgery, and need for additional blood product. Safety outcome was incidence of thrombotic events. RESULTS: There were 99 subjects included in the 4F-PCC group and 84 subjects in the AA group. Hemostatic efficacy was achieved in 69 subjects (69.7%) in the 4F-PCC group and 63 subjects (75%) in the AA group (P = 0.927). In-hospital mortality was seen in 20 subjects (20.2%) in the 4F-PCC group and 10 subjects (11.9%) in the AA group. Thrombotic events were seen in 7 subjects (7.1%) in the 4F-PCC group and 6 subjects (7.1%) in the AA group. CONCLUSIONS: There were no significant differences in hemostatic efficacy, in-hospital mortality, and number of thrombotic events between 4F-PCC and AA.
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Reversão da Anticoagulação , Fatores de Coagulação Sanguínea , Fator Xa , Hemostáticos , Proteínas Recombinantes , Adulto , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fatores de Coagulação Sanguínea/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Retrospective studies support that mean perfusion pressure (MPP) deficit in cardiac surgery patients is associated with a higher incidence of acute kidney injury (CS-AKI). The aim of our study was to apply an algorithm based on MPP in the postoperative period to determine whether management with an individualized target reduces the incidence of CS-AKI. METHODS: Randomized controlled trial of patients undergoing cardiac surgery with extracorporeal circulation. Adult patients submitted to valve replacement and/or bypass surgery with a high risk of CS-AKI evaluated by a Leicester score >30 were randomized to follow a target MPP of >75% of the calculated baseline or a standard hemodynamic management during the first postoperative 24 h. RESULTS: Ninety-eight patients with an eGFR of 54 mL/min were included. There were no differences in MAP and MPP in the first 24 h between the randomized groups, although a higher use of noradrenaline was found in the intervention arm (38.78 vs. 63.27, p = 0.026). The percentage of time with MPP < 75% of measured baseline was similar in both groups (10 vs. 12.7%, p = 0.811). MAP during surgery was higher in the intervention group (73 vs. 77 mmHg, p = 0.008). The global incidence of CS-AKI was 36.7%, being 38.6% in the intervention group and 34.6% in the control group (p = 0.40). There were no differences in extrarenal complications between groups as well. CONCLUSION: An individualized hemodynamic management based on MPP compared to standard treatment in cardiac surgery patients was safe but did not reduce the incidence of CS-AKI in our study.
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This research analyses how different cement mortars behave in terms of their physical and mechanical properties. Several components were necessary to make seven mixes of mortars, such as Portland cement, standard sand, and solid waste from a factory of sodium silicate, in addition to graphene oxide. Furthermore, graphene oxide (GO) was selected to reduce the micropores and increase the nanopores in the cement mortar. Hence, some tests were carried out to determine their density, humidity content, water absorption capacity, open void porosity, the alkali-silica reaction, as well as flexural and mechanical strength and acid resistance. Thus, standard-sand-manufactured mortars' mechanical properties were proved to be slightly better than those manufactured with recycled waste; the mortars with this recycled aggregate presented problems of alkali-silica reaction. In addition, GO (in a ratio GO/cement = 0.0003) performed as a filler, improving the mechanical properties (30%), alkali-silica (80%), and acid resistance.
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BACKGROUND: Robotic distal pancreatectomy (RDP) is associated with a lower conversion rate and less blood loss than laparoscopic distal pancreatectomy (LDP). LDP has similar oncological outcomes as open surgery in PDAC. The aim of this study was to compare perioperative and oncological outcomes in obese patients with RDP versus LDP for PDAC. MATERIALS AND METHODS: Retrospectively, all obese patients who underwent RDP or LDP for PDAC between 2012 and 2022 at 12 international expert centres were included. RESULTS: out of 372, 81 patients were included. All baseline features were comparable between the two groups. RDP was associated with decreased blood loss (495mlLDP vs. 188mlRDP; p = 0.003), lower conversion rate (13.5%RDP vs. 36.4%LDP; p = 0.019) and lower rate of Clavien-Dindo ≥3 complications (13.5%RDP vs. 36.4%LDP; p = 0.019). Overall and disease-free survival were comparable. CONCLUSIONS: In obese patients with left-sided PDAC, the robotic approach was associated with improved intraoperative outcomes and fewer severe complications.
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BACKGROUND: Elevated intracranial pressure is a devastating complication of catastrophic brain injury. Intracranial hypertension is commonly seen in neurologic injury secondary to traumatic brain injuries. Uncontrolled pressures can lead to permanent neurologic damage, but acute medical management is often overlooked when pursuing surgical management options that may not always be indicated. DISCUSSION: Traumatic brain injury is the leading cause of death in patients with severe neurologic injury. Diagnosing elevated intracranial pressures is imperative in initiating prompt treatment to reduce secondary central nervous system injury, morbidity, and mortality. Although the initial injury to the brain is typically irreversible, intracranial pressure control can assist in salvaging the remaining brain tissue from additional damage. We will discuss the initial medical and surgical management of traumatic brain injury to prevent further neurologic deterioration and reduce mortality. CONCLUSION: Recent literature has reported several methods to detect elevated intracranial pressure easily and studies describing multiple treatment modalities. These investigations suggest that early detection and timely treatment of intracranial hypertension are beneficial in reducing mortality.