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1.
Ann Palliat Med ; 13(2): 240-248, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462934

RESUMO

BACKGROUND: Hospice patients with end-stage liver disease (ESLD) have an increased risk of adverse drug events due to physiological changes and changes in pharmacokinetic and pharmacodynamic properties of medications; however, the use of opioid and central nervous system (CNS) depressant prescribing among patients with ESLD is prevalent. This study quantified the frequency and distribution of opioid and concomitant respiratory and CNS depressant prescribing among hospice patients with ESLD compared to other common hospice diagnoses of cancer, chronic obstructive pulmonary disorder (COPD), heart failure, and end-stage renal disease. METHODS: This was a cross-sectional study of adult (age 18 years or older) decedents of a large hospice chain. Patients included had a primary diagnosis of liver, cancer, cardiovascular, or respiratory disease. RESULTS: Among 119,424 hospice decedents, mean age of 77.9 years (standard deviation =13.5 years), 54.6% were female, and 58.9% were of a non-Hispanic white race. There was a similar frequency of prescribing a "scheduled" and "as needed [pro re nata (PRN)]" opioid or benzodiazepine in patients with ESLD compared to other common hospice diagnoses. In addition, there was a high prevalence of concurrent opioid and benzodiazepine prescriptions among patients with ESLD compared to cardiovascular and respiratory disease at admission (65.4% vs. 63.9% and 64.9%). Opioid requirements, oral morphine equivalent (OME) median [interquartile range (IQR)] at discharge were similar between cancer, liver, and respiratory disease, 120 OME [60-300], 120 OME [50-240], and 120 OME [50-240], respectively. CONCLUSIONS: We observed a high frequency of opioid and CNS depressant prescribing in a hospice patient population with ESLD which was similar to other common admitting hospice diagnoses.


Assuntos
Depressores do Sistema Nervoso Central , Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Adulto , Humanos , Feminino , Idoso , Adolescente , Masculino , Analgésicos Opioides/uso terapêutico , Alta do Paciente , Prevalência , Estudos Transversais , Depressão , Morfina , Benzodiazepinas , Neoplasias/tratamento farmacológico , Sistema Nervoso Central , Estudos Retrospectivos
2.
J Cardiopulm Rehabil Prev ; 44(1): 55-63, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37624048

RESUMO

PURPOSE: Despite the mortality benefit of cardiac rehabilitation (CR) participation, as well as its cost-effectiveness for people with peripheral artery disease (PAD), there are limited data on adherence and completion of CR in those with and without concomitant coronary artery disease (CAD). The objective of this study was to compare CR pre-participation withdrawal and noncompletion between patients with PAD and concomitant PAD and CAD (PAD/CAD) versus matched and unmatched patients with CAD (uCAD). METHODS: Consecutively referred patients between 2006-2017 with PAD (n = 271) and PAD/CAD (n = 610) were matched to CAD by age, sex, diabetes, smoking status, and referral year. The uCAD (n = 14 487) group was included for comparison. Reasons for withdrawal were ascertained by interview. RESULTS: There were no significant differences in pre-participation withdrawal between PAD and matched CAD (46 vs 43%, P = .49), nor in noncompletion (22 vs 18%, P = .28). Results were similar for PAD/CAD and matched CAD (withdrawal: 36 vs 34%, P = .37) and (noncompletion: 25 vs 23%, P = .46). A smaller proportion of patients with uCAD withdrew (28%) than patients with PAD ( P < .001) and PAD/CAD ( P < .001), with no difference in noncompletion ( P > .40, both). There were no differences between PAD and PAD/CAD and their matched counterparts for medical and nonmedical reasons for withdrawal and noncompletion ( P ≥ .25, all). CONCLUSION: Pre-participation withdrawal rates were similar between patients with PAD, PAD/CAD, and their matched cohorts but greater than patients with uCAD. Once patients started CR, there were similar completion rates among all groups. Reports that patients with PAD are less likely to start CR may be related to their complex medical profile rather than PAD alone. Strategies to improve participation among patients with PAD should focus on the immediate post-referral period.


Assuntos
Reabilitação Cardíaca , Doença da Artéria Coronariana , Diabetes Mellitus , Doença Arterial Periférica , Humanos , Doença da Artéria Coronariana/complicações , Doença Arterial Periférica/complicações , Fumar , Fatores de Risco
3.
J Lipid Res ; 65(1): 100486, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104944

RESUMO

Cholesterol is an essential structural component of all membranes of mammalian cells where it plays a fundamental role not only in cellular architecture, but also, for example, in signaling pathway transduction, endocytosis process, receptor functioning and recycling, or cytoskeleton remodeling. Consequently, intracellular cholesterol concentrations are tightly regulated by complex processes, including cholesterol synthesis, uptake from circulating lipoproteins, lipid transfer to these lipoproteins, esterification, and metabolization into oxysterols that are intermediates for bile acids. Oxysterols have been considered for long time as sterol waste products, but a large body of evidence has clearly demonstrated that they play key roles in central nervous system functioning, immune cell response, cell death, or migration and are involved in age-related diseases, cancers, autoimmunity, or neurological disorders. Among all the existing oxysterols, this review summarizes basic as well as recent knowledge on 25-hydroxycholesterol which is mainly produced during inflammatory or infectious situations and that in turn contributes to immune response, central nervous system disorders, atherosclerosis, macular degeneration, or cancer development. Effects of its metabolite 7α,25-dihydroxycholesterol are also presented and discussed.


Assuntos
Hidroxicolesteróis , Oxisteróis , Animais , Hidroxicolesteróis/metabolismo , Colesterol/metabolismo , Transporte Biológico , Lipoproteínas/metabolismo , Mamíferos/metabolismo
5.
Nat Neurosci ; 26(9): 1505-1515, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37563294

RESUMO

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Humanos , Transtorno Autístico/genética , Transtorno do Espectro Autista/patologia , Neurônios/metabolismo , Neurogênese , Prosencéfalo/metabolismo , Organoides/metabolismo
7.
Commun Biol ; 6(1): 444, 2023 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-37087494

RESUMO

Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice.


Assuntos
Linfócitos T CD8-Positivos , Linfoma de Células B , Humanos , Camundongos , Animais , Receptores de Antígenos de Linfócitos T/metabolismo , Células Jurkat , Linfoma de Células B/metabolismo
8.
Can Commun Dis Rep ; 49(1): 282-287, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38444981

RESUMO

Rabies vaccines are highly effective and immunogenic in most populations, including when used as rabies post-exposure prophylaxis (RPEP); however, there is mounting evidence that the immune response to rabies vaccines, though predicted to be adequate, may be lower in older adults. Despite this, there are no specific recommendations in Canadian guidance to monitor the serological response of older adults following RPEP. Furthermore, while Canadian guidance recommends the intramuscular route for RPEP vaccination, there is good evidence supporting the immunogenicity, effectiveness and safety of RPEP vaccination using the intradermal route. We present a case of an 87-year-old male with rabies exposure who failed to respond to two series of RPEP with intramuscular rabies vaccination but responded to a third series using intradermal vaccine administration and provide reasoning for subsequent management. This case is brought forward to prompt discussion and research as to the utility of completing serology in older adults receiving RPEP as well as vaccination strategies, including route of administration, in those who do not respond to an initial course of RPEP vaccination.

9.
Front Endocrinol (Lausanne) ; 13: 964681, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465660

RESUMO

Misalignment between the environment and one's circadian system is a common phenomenon (e.g., jet lag) which can have myriad negative effects on physical and mental health, mental and physiological performance, and sleep. Absent any intervention, the circadian system adjusts only 0.5-1.0 h per day to a shifted light-dark and sleep-wake schedule. Bright light facilitates circadian adjustment, but in field studies, bright light is only modestly better than no stimulus. Evidence indicates that exercise and melatonin can be combined with bright light to elicit larger shifts but no study has combined all of these stimuli or administered them at the times that are known to elicit the largest effects on the circadian system. The aims of this study are to compare the effects of different treatments on circadian adjustment to simulated jet lag in a laboratory. Following 2 weeks of home recording, 36 adults will spend 6.5 consecutive days in the laboratory. Following an 8 h period of baseline sleep recording on the participant's usual sleep schedule on Night 1 (e.g., 0000-0800 h), participants will undergo a 26 h circadian assessment protocol involving 2 h wake intervals in dim light and 1 h of sleep in darkness, repeated throughout the 26 h. During this protocol, all urine voidings will be collected; mood, sleepiness, psychomotor vigilance, and pain sensitivity will be assessed every 3 h, forehead temperature will be assessed every 90 min, and anaerobic performance (Wingate test) will be tested every 6 h. Following, the circadian assessment protocol, the participant's sleep-wake and light dark schedule will be delayed by 8 h compared with baseline (e.g., 0800-1400 h), analogous to travelling 8 times zones westward. This shifted schedule will be maintained for 3 days. During the 3 days on the delayed schedule, participants will be randomized to one of 3 treatments: (1) Dim Red Light + Placebo Capsules, (2) Bright Light Alone, (3) Bright Light + Exercise + Melatonin. During the final 26 h, all conditions and measures of the baseline circadian protocol will be repeated. Acclimatization will be defined by shifts in circadian rhythms of aMT6s, psychomotor vigilance, Wingate Anaerobic performance, mood, and sleepiness, and less impairments in these measures during the shifted schedule compared with baseline. We posit that Bright Light Alone and Bright Light + Exercise + Melatonin will elicit greater shifts in circadian rhythms and less impairments in sleep, mood, performance, and sleepiness compared with Dim Red Light + Placebo Capsules. We also posit that Bright Light + Exercise + Melatonin will elicit greater shifts and less impairments than Bright Light Alone.


Assuntos
Melatonina , Adulto , Humanos , Sonolência , Síndrome do Jet Lag , Sono , Aclimatação
10.
Health Promot Pract ; : 15248399221137804, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482665

RESUMO

Movement as medicine is the premise behind Running Medicine (RM), a community-based wellness program that began in 2016 in New Mexico. RM is centered in the Indigenous traditions of running and is oriented to improving the four dimensions of wellness-mind, body, spirit, and social. Using retroactive surveys of RM's Spring 2019 participants, we investigated the program's effectiveness in the realms of physical, mental, spiritual, and social wellness. Based on data from participant surveys, RM appears to be effective at improving the four realms of wellness. Indigenous participants improved to a greater degree in mental and social wellness than non-Indigenous participants, while the opposite was true for physical and spiritual wellness. For both groups, the largest effect size among the four domains was seen in social wellness. Among our participants, this culturally grounded approach to wellness appears to be effective at improving the four realms of physical, mental, spiritual, and social wellness.

11.
Biomolecules ; 12(11)2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36358934

RESUMO

Hypothermic (cold) preservation is a limiting factor for successful cell and tissue transplantation where cell swelling (edema) usually develops, impairing cell function. University of Wisconsin (UW) solution, a standard cold preservation solution, contains effective components to suppress hypothermia-induced cell swelling. Antifreeze proteins (AFPs) found in many cold-adapted organisms can prevent cold injury of the organisms. Here, the effects of a beetle AFP from Dendroides canadensis (DAFP-1) on pancreatic ß-cells preservation were first investigated. As low as 500 µg/mL, DAFP-1 significantly minimized INS-1 cell swelling and subsequent cell death during 4 °C preservation in UW solution for up to three days. However, such significant cytoprotection was not observed by an AFP from Tenebrio molitor (TmAFP), a structural homologue to DAFP-1 but lacking arginine, at the same levels. The cytoprotective effect of DAFP-1 was further validated with the primary ß-cells in the isolated rat pancreatic islets in UW solution. The submilligram level supplement of DAFP-1 to UW solution significantly increased the islet mass recovery after three days of cold preservation followed by rewarming. The protective effects of DAFP-1 in UW solution were discussed at a molecular level. The results indicate the potential of DAFP-1 to enhance cell survival during extended cold preservation.


Assuntos
Besouros , Animais , Ratos , Besouros/química , Besouros/metabolismo , Sobrevivência Celular , alfa-Fetoproteínas/farmacologia , Proteínas Anticongelantes/química , Glutationa/farmacologia , Insulina/farmacologia , Edema
12.
Medicine (Baltimore) ; 101(42): e31058, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281145

RESUMO

The COVID-19 pandemic reached the United States in early 2020 and spread rapidly across the country. This retrospective study describes the demographic and clinical characteristics of 308 children presenting to an Arkansas Children's emergency department (ED) or admitted to an Arkansas Children's hospital with COVID-19 in the first 10 months of the COVID-19 pandemic, prior to the emergence of clinically significant variants and available vaccinations. Adolescents aged 13 and older represented the largest proportion of this population. The most common presenting symptoms were fever, gastrointestinal symptoms, and upper respiratory symptoms. Patients with multisystem inflammatory syndrome in children (MIS-C) had a longer length of stay (LOS) than patients with acute COVID-19. Children from urban zip codes had lower odds of admission but were more likely to be readmitted after discharge. Nearly twenty percent of the study population incidentally tested positive for COVID-19. Despite lower mortality in children with COVID than in adults, morbidity and resource utilization are significant. With many Arkansas children living in rural areas and therefore far from pediatric hospitals, community hospitals should be prepared to evaluate children presenting with COVID-19 and to determine which children warrant transport to pediatric-specific facilities.


Assuntos
COVID-19 , Adolescente , Adulto , Criança , Humanos , Estados Unidos , COVID-19/epidemiologia , Pandemias , Estudos Retrospectivos , Arkansas/epidemiologia , Morbidade
13.
J Vasc Interv Radiol ; 33(12): 1559-1569.e2, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36084842

RESUMO

PURPOSE: To assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: A systematic search of the Embase and MEDLINE databases was conducted using keywords and Medical Subject Headings terms related to TARE and hepatic metastases from PDAC. Observational studies and clinical trials reporting overall survival (OS), hepatic progression-free survival (hPFS), or tumor response after TARE were included. RESULTS: Eight studies, comprising 145 patients with metastatic PDAC, met the inclusion criteria. No randomized controlled trials were identified, and 4 studies were prospective. Forty-four (30.3%) patients underwent previous pancreatic resection, and 66 (45.5%) had extrahepatic metastases at the time of TARE. Most studies (n = 6) used resin microspheres for TARE. The pooled disease control rate was 69.4% at a median of 3 months. The median OS from the time of TARE ranged from 3.7 to 9 months. The median hPFS ranged from 2.4 to 5.2 months. There were 31 Grade 3-4 biochemical toxicities and 4 treatment-related deaths. CONCLUSIONS: The role of TARE in patients with hepatic metastases from PDAC remains unclear owing to low patient numbers, limited prospective data, and heterogeneity in the study design. Further prospective studies are required to evaluate the role of TARE in carefully selected patients with liver-only metastatic disease.


Assuntos
Adenocarcinoma , Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Embolização Terapêutica , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Radioisótopos de Ítrio/efeitos adversos , Adenocarcinoma/terapia , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Embolização Terapêutica/efeitos adversos , Carcinoma Hepatocelular/terapia , Estudos Retrospectivos , Neoplasias Pancreáticas
14.
J Plast Reconstr Aesthet Surg ; 75(11): 4264-4272, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36127225

RESUMO

BACKGROUND: The incidence of facial skin cancer increases worldwide, resulting in more surgical resections and reconstructions. Reconstructive surgery aims to approach a normal facial anatomy to optimize the quality of life. Objective automated assessment of the esthetic outcome of facial reconstructions could provide feedback for the improvement of surgical techniques and preoperative patient expectation management. OBJECTIVE: This systematic literature review aimed to assess whether modern technologies can create automated objective measurements of surgical and non-surgical facial interventions outcomes using 3D surface imaging technology. METHODS: A systematic literature search was conducted in Embase, Medline (Ovid), Web of Science, and Cochrane on May 19, 2021. All English literature was collected on surgical and non-surgical invasive facial interventions in which 3D surface imaging technology was used for objective automated assessment of outcomes. RESULTS: Fourteen articles were included in the systematic review. 3D surface imaging technology and automated assessment techniques were found for skin malignancy, cleft lip repair, rhinoplasty, orthognathic surgery, and injectables. Ten 3D surface imaging technology hardware systems and 12 software systems were described. Four studies compared 3D surface imaging techniques to conventional methods. Ten studies used 3D surface imaging techniques for the evaluation of the surgical outcome, without comparison to 2D photography, validated scores, or a panel. Two studies validated the hardware system. CONCLUSION: This systematic literature review shows that 3D surface imaging technology has the potential for automated objective assessment of facial intervention outcomes. Future studies are necessary to study and validate these tools for standard clinical use in patients with facial interventions.


Assuntos
Fenda Labial , Fissura Palatina , Humanos , Fissura Palatina/cirurgia , Qualidade de Vida , Fenda Labial/cirurgia , Face/diagnóstico por imagem , Face/cirurgia , Face/anatomia & histologia , Imageamento Tridimensional/métodos , Tecnologia
15.
Sci Rep ; 12(1): 10581, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732671

RESUMO

Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (db/db) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved fasting blood glucose levels, altered the response to exogenous insulin, and decreased circulating lipopolysaccharide and hepatic C-reactive protein transcript levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Microbiota , Rhodiola , Animais , Biomarcadores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inflamação/tratamento farmacológico , Camundongos , Camundongos Knockout , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores para Leptina/genética
16.
J Pain Palliat Care Pharmacother ; 36(1): 59-67, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35319327

RESUMO

The global prevalence of heart failure (HF) is increasing. Advancements in guideline-directed medical and device therapy have resulted in improved survival. Thus, there are more patients living - and living longer - with advanced HF. Only a small proportion of these patients are deemed appropriate for advanced surgical intervention (mechanical circulatory support or heart transplantation), and even if offered, some may decline such interventions if not aligned with their overall goals and values. Therefore, a growing number of patients with advanced HF receive chronic intravenous inotropic support (CIIS) for palliation of symptoms. Despite increased use, clinical evidence supporting use of palliative inotropes remains limited. However, available data suggest improvements in functional class, health-related quality of life (HRQoL) indicators, symptom burden, hemodynamic parameters, and possibly rehospitalization. While initial concerns regarding increased mortality have been assuaged in the modern era of guideline-directed medical therapy, palliative inotropes are certainly not without burden. Risks of infection and medication-related adverse effects, need for routine laboratory monitoring, frequent dressing changes, and presence of a reliable caregiver must be carefully considered prior to initiation. This review addresses pharmacology, guideline recommendations, benefits and burdens, considerations related to hospice and end-of-life care, and future directions of CIIS in advanced HF care.


Assuntos
Insuficiência Cardíaca , Cuidados Paliativos na Terminalidade da Vida , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Cuidados Paliativos , Qualidade de Vida
17.
Toxins (Basel) ; 14(2)2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35202128

RESUMO

The uremic toxin indoxyl sulfate (IS), elevated in chronic kidney disease (CKD), is known to contribute towards progressive cardiovascular disease. IS activates the aryl hydrocarbon receptor (AhR) mediating oxidative stress and endothelial dysfunction via activation of the CYP1A1 pathway. The present study examines AhR inhibition with the antagonist, CH223191, on IS-mediated impairment of vascular endothelial function and disruption of redox balance. The acute effects of IS on endothelium-dependent relaxation were assessed in aortic rings from Sprague Dawley rats exposed to the following conditions: (1) control; (2) IS (300 µM); (3) IS + CH223191 (1 µM); (4) IS + CH223191 (10 µM). Thereafter, tissues were assessed for changes in expression of redox markers. IS reduced the maximum level of endothelium-dependent relaxation (Rmax) by 42% (p < 0.001) compared to control, this was restored in the presence of increasing concentrations of CH223191 (p < 0.05). Rings exposed to IS increased expression of CYP1A1, nitro-tyrosine, NADPH oxidase 4 (NOX4), superoxide, and reduced eNOS expression (p < 0.05). CH223191 (10 µM) restored expression of these markers back to control levels (p < 0.05). These findings demonstrate the adverse impact of IS-mediated AhR activation on the vascular endothelium, where oxidative stress may play a critical role in inducing endothelial dysfunction in the vasculature of the heart and kidneys. AhR inhibition could provide an exciting novel therapy for CVD in the CKD setting.


Assuntos
Aorta Torácica/efeitos dos fármacos , Compostos Azo/farmacologia , Endotélio Vascular/efeitos dos fármacos , Indicã/farmacologia , Pirazóis/farmacologia , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , Citocromo P-450 CYP1A1/genética , Endotélio Vascular/fisiologia , Expressão Gênica/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica , Vasodilatação/efeitos dos fármacos
18.
Life Sci ; 289: 120220, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34902438

RESUMO

AIMS: Myocardial injury is a major contributor to left ventricular (LV) remodelling activating neurohormonal and inflammatory processes that create an environment of enhanced oxidative stress. This results in geometric and structural alterations leading to reduced LV systolic function. In this study we evaluated the efficacy of NP202, a synthetic flavonol, on cardiac remodelling in a chronic model of myocardial infarction (MI). MAIN METHODS: A rat model of chronic MI was induced by permanent surgical ligation of the coronary artery. NP202 treatment was commenced 2 days post-MI for 6 weeks at different doses (1, 10 and 20 mg/kg/day) to determine efficacy. Cardiac function was assessed by echocardiography prior to treatment and at week 6, and pressure-volume measurements were performed prior to tissue collection. Tissues were analysed for changes in fibrotic and inflammatory markers using immunohistochemistry and gene expression analysis. KEY FINDINGS: Rats treated with NP202 demonstrated improved LV systolic function and LV geometry compared to vehicle treated animals. Furthermore, measures of hypertrophy and interstitial fibrosis were attenuated in the non-infarct region of the myocardium with NP202 at the higher dose of 20 mg/kg (P < 0.05). At the tissue level, NP202 reduced monocyte chemoattractant protein-1 expression (P < 0.05) and tended to attenuate active caspase-3 expression to similar levels observed in sham animals (P = 0.075). SIGNIFICANCE: Improved LV function and structural changes observed with NP202 may be mediated through inhibition of inflammatory and apoptotic processes in the MI setting. NP202 could therefore prove a useful addition to standard therapy in patients with post-MI LV dysfunction.


Assuntos
Flavonoides/farmacologia , Infarto do Miocárdio , Miocárdio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Caspase 3/biossíntese , Quimiocina CCL2/biossíntese , Doença Crônica , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Sprague-Dawley
19.
Stroke ; 53(4): 1216-1225, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34781705

RESUMO

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Resultado do Tratamento
20.
Ann Vasc Surg ; 77: 306-314, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34437976

RESUMO

BACKGROUND: Endovascular aneurysm repair (EVAR) is an established treatment for many patients with infra-renal abdominal aortic aneurysm (AAA). Reporting standards were published in 2002 to ensure consistent measurement and reporting of outcomes following EVAR. We aimed to assess the range of clinical outcomes reported after EVAR and whether recent studies adhere to established reporting standards. METHODS: We searched MEDLINE and Embase from January 2014 until December 2018, using terms for 'EVAR' and 'AAA'. We included prospective studies and randomised controlled trials which reported clinical outcomes of elective infra-renal AAA repair. Data on clinical outcome reporting were extracted and compared with established reporting standards. RESULTS: 84 studies were included. Technical success was reported in 49 (58.3%) studies, but only defined in 40 (47.6%), with 22 distinct definitions. Clinical success was reported and defined in 19 (22.6%) studies. Aneurysm rupture was reported in 27 (32.1%) studies and death from rupture in 11 (13.1%) studies. All-cause and aneurysm-related mortality were reported in 72 (85.7%) and 52 (61.9%) studies, respectively. Endoleak type I (n = 61, 72.6%) and II (n = 52, 61.9%) were more commonly reported than type III (n = 45, 53.6%) or IV (n = 13, 15.5%). Complications and mortality were reported by a mean of 18 (21.4%) and 42 (50%) studies, respectively. CONCLUSIONS: A wide variety of clinical outcomes were reported following EVAR. Few studies adhered to reporting guidelines. We recommend modification of reporting standards to reflect advances in endovascular technology and creation of a core outcome set for EVAR.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Registros Públicos de Dados de Cuidados de Saúde , Indicadores de Qualidade em Assistência à Saúde , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Implante de Prótese Vascular/normas , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Procedimentos Endovasculares/normas , Fidelidade a Diretrizes , Mortalidade Hospitalar , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Guias de Prática Clínica como Assunto , Indicadores de Qualidade em Assistência à Saúde/normas , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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