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BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.
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Lesões do Sistema Vascular , Humanos , Animais , Camundongos , Suínos , Porco Miniatura , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética/métodos , Angioplastia , Inflamação/diagnóstico por imagem , Inflamação/etiologiaRESUMO
BACKGROUND: Hematological inflammatory parameters, including neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, are good predictors of postoperative pulmonary complications after lung cancer resection. However, the clinical value of the systemic immune-inflammation index has not been extensively studied. METHODS: We retrospectively analyzed a cohort of patients that underwent lung cancer resection in our center, and we analyzed the hematological inflammatory parameters (including systemic immune-inflammation index) and postoperative pulmonary complications after lung cancer resection. The receiver operating characteristic curve was applied to determine the best cut-off value. Multivariable analysis was applied to assess which of the factors was the most important. RESULTS: Two hundred and four patients were enrolled in this study. Of these, 47 postoperative pulmonary complications events were observed in 40 patients in this cohort. Surgery method, white blood cell count, albumin, forced expiratory volume in 1 second, carbon monoxide diffusing capacity, intensive care unit stay, and systemic immune-inflammation index were found to be significantly different between the postoperative pulmonary complications and non-postoperative pulmonary complications groups. We then used the receiver operating characteristic curves and the Youden index to determine the best cutoff value. Multivariable analysis revealed that systemic immune-inflammation index and forced expiratory volume in 1 second were the most important predictive factors of postoperative pulmonary complications after lung cancer resection. CONCLUSION: Hematological inflammatory parameters of systemic immune-inflammation index and forced expiratory volume in 1 second could be a favorable index to predict postoperative pulmonary complications after lung cancer resection.
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Neoplasias Pulmonares , Pneumonectomia , Humanos , Inflamação/complicações , Inflamação/etiologia , Neoplasias Pulmonares/etiologia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Capacidade de Difusão Pulmonar , Estudos RetrospectivosRESUMO
Methyl phydroxycinnamate (MH), an esterified derivative of pCoumaric acid exerts antiinflammatory effects on lipopolysaccharide (LPS)stimulated RAW264.7 macrophages. Based on these effects, the present study investigated the protective role of MH in a mouse model of LPSinduced acute respiratory distress syndrome (ARDS). The results demonstrated that administration of LPS (5 mg/kg intranasally) markedly increased the neutrophil/macrophage numbers and levels of inflammatory molecules (TNFα, IL6, IL1ß and reactive oxygen species) in the bronchoalveolar lavage ï¬uid (BALF) of mice. On histological examination, the presence of inflammatory cells was observed in the lungs of mice administered LPS. LPS also notably upregulated the secretion of monocyte chemoattractant protein1 and protein content in BALF as well as expression of inducible nitric oxide synthase in the lungs of mice; it also caused activation of p38 mitogenactivated protein kinase (MAPK) and NFκB signaling. However, MH treatment significantly suppressed LPSinduced upregulation of inflammatory cell recruitment, inflammatory molecule levels and p38MAPK/NFκB activation, and also led to upregulation of heme oxygenase1 (HO1) expression in the lungs of mice. In addition, the ability of MH to induce HO1 expression was confirmed in RAW264.7 macrophages. Taken together, the findings of the present study indicated that MH may exert protective effects against airway inflammation in ARDS mice by inhibiting inflammatory cell recruitment and the production of inflammatory molecules.
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Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Transdução de SinaisRESUMO
PURPOSE: Racial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19. METHODS: We leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in COVID-19 clinical trials, mortality, need for renal replacement therapy, and need for mechanical ventilation. RESULTS: Compared to non-Black patients, Black patients had a higher prevalence of COVID-19 risk factors including obesity, hypertension, and diabetes mellitus and were more likely to require renal replacement therapy (15.8% vs 7.1%, P < .001) and mechanical ventilation (37.2% vs 26.6%, P < .001) during their hospitalization. Mortality was similar between both groups (15.5% for Blacks vs 14.0% for non-Blacks, P = .49). Black patients were less likely to receive corticosteroids (44.9% vs 63.8%, P< .001) or remdesivir (23.8% vs 57.8%, P < .001) and were less likely to be enrolled in COVID-19 clinical trials (15.3% vs 28.2%, P < .001). In adjusted analyses, Black race was associated with lower levels of C-reactive protein and soluble urokinase receptor and higher odds of death, mechanical ventilation, and renal replacement therapy. Differences in outcomes were not significant after adjusting for use of remdesivir and corticosteroids. CONCLUSIONS: Racial differences in outcomes of patients with COVID-19 may be related to differences in inflammatory response and differential use of therapies.
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Negro ou Afro-Americano , COVID-19/complicações , COVID-19/terapia , Inflamação/etiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS). DESIGN AND METHODS: We investigated 2 cohorts: MHDltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m2) and MHDBrazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m2), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition. RESULTS: Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHDItaly cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHDBrazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHDItaly: κ = 0.26, P = .003; MHDBrazil: κ = 0.22, P = .003) and between GLIM and MIS (MHDItaly: κ = 0.33, P < .001; MHDBrazil: κ = 0.25, P = .001). Cox regression analysis showed that all 3 methods were able to predict mortality in crude analysis; however in the adjusted model, the association seemed more consistent and stronger in magnitude for 7p-SGA and MIS. CONCLUSION: In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting.
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Desnutrição , Avaliação Nutricional , Adulto , Idoso , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Liderança , Masculino , Desnutrição/diagnóstico , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Diálise Renal/efeitos adversosRESUMO
Background Dual-energy CT enterography (DECTE) has been shown to be useful in characterizing Crohn disease activity compared with clinical markers of inflammation but, to the knowledge of the authors, comparison has not been made with histopathologic specimens. Purpose To compare mucosal iodine density obtained at DECTE from Crohn disease-affected bowel with histopathologic specimens from surgically resected ileocolectomy bowel segments or terminal ileum colonoscopic biopsies in the same patients. Materials and Methods This was a retrospective study. Bowel segments in adults with Crohn disease who underwent DECTE from January 2017 to April 2019 within 90 days of ileocolectomy or colonoscopy were retrospectively evaluated with prototype software allowing the semiautomatic determination of inner hyperdense bowel wall (mucosal) mean iodine density, normalized to the aorta. Mean normalized iodine density and clinical activity indexes (Crohn Disease Activity Index [CDAI] and Harvey-Bradshaw Index [HBI]) were compared with histologic active inflammation grades by using two-tailed t tests. Receiver operating characteristic curves were generated for mean normalized iodine density, CDAI, and HBI to determine sensitivity, specificity, and accuracy. A P value less than .05 was considered to indicate statistical significance. Results The following 16 patients were evaluated (mean age, 41 years ± 14 [standard deviation]): 10 patients (five men, five women; mean age, 41 years ± 15) with 19 surgical resection specimens and six patients with terminal ileum colonoscopic mucosal biopsies (four men, two women; mean age, 43 years ± 14). Mean normalized iodine density was 16.5% ± 5.7 for bowel segments with no active inflammation (n = 8) and 34.7% ± 9.7 for segments with any active inflammation (n = 17; P < .001). A 20% mean normalized iodine density threshold had sensitivity, specificity, and accuracy of 17 of 17 (100%; 95% CI: 80.5, 100), six of eight (75%; 95% CI: 35, 97), and 23 of 25 (92%; 95% CI: 74, 99), respectively, for active inflammation. Clinical indexes were similar for patients with and without active inflammation at histopathologic analysis (CDAI score, 261 vs 251, respectively [P = .77]; HBI score, 7.8 vs 6.4, respectively [P = .36]). Conclusion Iodine density from dual-energy CT enterography may be used as a radiologic marker of Crohn disease activity as correlated with histopathologic analysis. © RSNA, 2021 See also the editorial by Ohliger in this issue.
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Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Inflamação/diagnóstico por imagem , Inflamação/patologia , Iodo/farmacocinética , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Biomarcadores , Meios de Contraste/farmacocinética , Doença de Crohn/complicações , Feminino , Humanos , Inflamação/etiologia , Intestinos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Among Black Americans, interpersonal racial discrimination is common. Stress, including following discrimination, contributes to pregnancy complications. In this secondary analysis, we provide data on associations among discrimination, stress, and their interaction across the life course and inflammation, perceived stress, and depressive symptoms during pregnancy. METHODS: During the early third trimester, Black American women (n = 93) completed the Experiences of Discrimination Scale, the Stress and Adversity Inventory, the Perceived Stress Scale, and the Center for Epidemiological Studies Depression Inventory. Plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and IL-ß levels were quantified. Associations were examined by linear regression, controlling for demographic, behavioral, and clinical covariates. RESULTS: Associations among racial discrimination and plasma IL-8, TNF-α, and IL-ß levels depended upon average ratings of life course stress. When stress was low, discrimination in the mid tertile was associated with the highest levels of IL-8, TNF-α, and IL-ß. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-ß were driven by acute stress. When examined together, greater discrimination but not greater life course stress was associated with higher prenatal perceived stress. In subscale analyses, the association between discrimination and prenatal perceived stress depended upon average ratings of life course acute stress. When acute stress was low, discrimination in the midtertile was associated with the highest levels of prenatal perceived stress. When acute stress was high, discrimination in the high tertile was associated with the highest levels of prenatal perceived stress. There were also direct associations among greater life course chronic stress, prenatal perceived stress, and prenatal depressive symptoms. Associations were attenuated when discrimination was included as a covariate. CONCLUSIONS: The current analyses suggest that, among Black Americans, prenatal inflammation, perceived stress, and depressive symptoms may be shaped by racial discrimination and stress across the life course. In many cases, associations among discrimination and prenatal parameters depended upon how stressful exposures to life course stressors had been rated. The data suggest the potential for adaptive plasticity under some stress and highlight the deleterious nature of compounding stress.
Assuntos
Depressão/psicologia , Racismo/psicologia , Estresse Psicológico/etiologia , Adolescente , Adulto , Negro ou Afro-Americano , Depressão/etnologia , Depressão/etiologia , Feminino , Humanos , Inflamação/classificação , Inflamação/etnologia , Inflamação/etiologia , Modelos Lineares , Masculino , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/etiologia , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/psicologia , Cuidado Pré-Natal/estatística & dados numéricos , Racismo/etnologia , Racismo/estatística & dados numéricos , Fatores Socioeconômicos , Estresse Psicológico/psicologiaRESUMO
PURPOSE: To determine the thermographic parameters of ocular surface tissues in various types of anti-glaucoma operations. MATERIAL AND METHODS: The study included 70 patients with glaucoma (140 eyes) and 28 patients (56 eyes) with cataract and planned phacoemulsification. All patients underwent dynamic infrared thermography of the eye surface to evaluate the aseptic inflammatory response before and after surgery. RESULTS: The increase in the temperature of the ocular surface tissues was longer after penetrating glaucoma surgery than after the non-penetrating type, which indicates a more prolonged inflammatory aseptic reaction in response to surgical intervention. CONCLUSION: The obtained results allow the development of a rational tactic of preoperative drug preparation and more effective postoperative management.
Assuntos
Catarata , Facoemulsificação , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Facoemulsificação/efeitos adversos , Período Pós-Operatório , TermografiaRESUMO
OBJECTIVE: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.
Assuntos
Disparidades nos Níveis de Saúde , Mediadores da Inflamação/sangue , Inflamação/etiologia , Síndrome Metabólica/etiologia , Obesidade/complicações , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Células Cultivadas , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Interleucina-6/sangue , Leptina/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Metabolômica , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: It has been suggested that adverse socioeconomic conditions "get under the skin" by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships. METHODS: In this cross-sectional study (n = 102), participants (20-59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations. SEP was characterized by annual household income and educational attainment. Cortisol, a biological correlate of chronic stress, was assessed in hair samples. Oral immunity was characterized by assessing oral inflammatory load and proinflammatory oral neutrophil function. Blockwise Poisson and logistic regression models were applied. RESULTS: Compared with lower SEP, individuals in the middle- and higher-income categories had a significantly lower probability of PD (incidence rate ratio [IRR] = 0.5 [confidence interval {CI} = 0.3-0.7] and IRR = 0.4 [95% CI = 0.2-0.7]) and oral inflammatory load (IRR = 0.6 [95% CI = 0.3-0.8] and IRR = 0.5 [95% CI = 0.3-0.7]) and were less likely to have a proinflammatory oral immune function (odds ratio [OR] = 0.1 [95% CI = 0.0-0.7] and OR = 0.1 [95% CI = 0.0-0.9]). PD and oral immune parameters were significantly associated with financial stress and cortisol. Adjusting for financial stress and cortisol partially attenuated the socioeconomic differences in PD to IRR = 0.7 (95% CI = 0.5-0.8) and IRR = 0.6 (95% CI = 0.5-0.7) for the middle- and higher-income categories, respectively. Similar results were observed for proinflammatory immunity (OR = 0.2 [95% CI = 0.0-1.8] and OR = 0.3 [95% CI = 0.0-2.3]). CONCLUSION: These findings suggest that psychosocial stress may contribute to a proinflammatory immunity that is implicated in PD pathobiology and provide insight into social-to-biological processes in oral health.
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Inflamação/epidemiologia , Boca/imunologia , Doenças Periodontais/epidemiologia , Classe Social , Estresse Psicológico/epidemiologia , Adulto , Estudos Transversais , Feminino , Cabelo/química , Humanos , Hidrocortisona/metabolismo , Inflamação/etiologia , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos , Doenças Periodontais/etiologia , Doenças Periodontais/imunologia , Estresse Psicológico/complicações , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo , Adulto JovemRESUMO
AIM: The aim of this study is to examine the relationship between inflammatory markers, and diabetic retinopathy in type II diabetic patients. METHODS: The study was a cross-sectional study included 150 type 2 diabetic patients who were divided into 3 groups. 50 in each group are divided as Diabetic patients without retinopathy (DM, n=50), nonproliferative diabetic retinopathy patients (NPDR, n=50), proliferative diabetic retinopathy patients (PDR, n=50). All the patients were subjected to complete clinical examination and laboratory investigations, such as fasting and postprandial blood glucose, serum creatinine, lipid profile tests, glycosylated haemoglobin (HbA1c), fasting insulin, serum inflammatory markers (TNF-alpha, C-reactive protein) and serum VEGF. RESULTS: The study revealed from the multivariate analysis that age, duration and WHR (waist-hip ratio) are potent risk factors responsible for the risk of Diabetic retinopathy. Similarly, serum creatinine, CRP, TNF- alpha and VEGF are significantly higher in diabetic patients with retinopathy compared to diabetic patients without retinopathy. CONCLUSION: The study concluded that inflammation was associated with severe diabetic retinopathy in patients with well-controlled diabetes. A possible relationship was provided between the risk factors and biomarkers which are responsible for Diabetic retinopathy. Hence, modifying the risk factors risk and development of severe diabetic retinopathy can be reduced.
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Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Inflamação/sangue , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/etiologia , Progressão da Doença , Hemoglobinas Glicadas/análise , Humanos , Inflamação/etiologia , Medição de Risco , Fatores de RiscoRESUMO
Much research finds that early life socioeconomic disadvantage predicts poorer health later in life, even among those whose conditions improve in adulthood. Although there are numerous factors that contribute to this association, recent research suggests that growing up in adverse socioecological environments may promote developmental patterns that facilitate pre-reproductive survival in harsh environments, but can also come at the cost of reduced longevity. Here, we review recent research demonstrating that early life exposure to low socioeconomic status can become embedded in the mechanisms that regulate (a) bodily inflammatory activity and (b) energy regulation in ways that contribute to poor health. This research offers new insights into ways that early life environments can get under one's skin to impact health and longevity.
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Experiências Adversas da Infância , Disparidades nos Níveis de Saúde , Desenvolvimento Humano , Inflamação , Meio Social , Fatores Socioeconômicos , Populações Vulneráveis , Desenvolvimento Humano/fisiologia , Humanos , Inflamação/etiologiaRESUMO
PURPOSE: Zilver PTX nitinol self-expanding drug-eluting stent with paclitaxel coating is effective for treatment of superficial femoral artery (SFA) disease. However, as with any stent, it induces a measure of vascular inflammatory response. The current clinical trial (NCT02734836) aimed to assess vascular patency, remodeling, and inflammatory markers with intravascular optical coherence tomography (OCT) in patients with SFA disease treated with Zilver PTX stents. METHODS: Serial OCT examinations were performed in 13 patients at baseline and 12-month follow-up. Variables evaluated included neointimal area, luminal narrowing, thrombus area, stent expansion as well as measures of inflammation including, peri-strut low-intensity area (PLIA), macrophage arc, neovascularization, stent strut apposition and coverage. RESULTS: Percentage of malapposed struts decreased from 10.3⯱â¯7.9% post-intervention to 1.1⯱â¯2.2% at 12-month follow-up, but one patient showed late-acquired stent malapposition (LASM). The percent of uncovered struts at follow-up was 3.0⯱â¯4.5%. Average expansion of stent cross-sectional area from baseline to follow-up was 35⯱â¯19%. The average neointimal area was 7.8⯱â¯3.8â¯mm2. Maximal luminal narrowing was 61.1⯱â¯25.0%, and average luminal narrowing was 35.4⯱â¯18.2%. Average peri-strut low-intensity area (PLIA) per strut was 0.017⯱â¯0.018â¯mm2. Average number of neovessels per mm of stent was 0.138⯱â¯0.181. Average macrophage angle per frame at follow-up was 7⯱â¯11°. Average thrombus area at follow-up was 0.0093⯱â¯0.0184â¯mm2. CONCLUSION: At 12-month follow-up, OCT analysis of Zilver PTX stent shows outward remodeling and minimal neointimal growth, but evidence of inflammation including PLIA, neovessels, thrombus and macrophages. SUMMARY: Thirteen patients with PAD had paclitaxel-coated stents implanted in their SFAs and were then imaged with OCT at baseline and 12-month follow-up. OCT proxy metrics of inflammation were quantified.
Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Stents Farmacológicos , Artéria Femoral/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Stents Metálicos Autoexpansíveis , Tomografia de Coerência Óptica , Grau de Desobstrução Vascular , Idoso , Idoso de 80 Anos ou mais , Ligas , Angioplastia com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Feminino , Artéria Femoral/fisiopatologia , Humanos , Inflamação/etiologia , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neointima , Paclitaxel/efeitos adversos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Remodelação VascularRESUMO
OBJECTIVES: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. DESIGN: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. SETTING: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: Children with severe sepsis and indwelling arterial or central venous catheters. INTERVENTIONS: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. MEASUREMENTS AND MAIN RESULTS: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08). CONCLUSIONS: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.
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Inflamação/etiologia , Inflamação/fisiopatologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Sepse/complicações , Adolescente , Cateteres de Demora , Criança , Pré-Escolar , Cuidados Críticos , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Falência Hepática/etiologia , Masculino , Paralisia/etiologia , Fenótipo , Estudos Prospectivos , Sepse/fisiopatologia , Trombocitopenia/etiologiaRESUMO
We investigated the effect of muscle damage and inflammation on electrical resistance and the body composition assessment by using bioimpedance spectroscopy (BIS). Twenty-two subjects completed 30 repetitions of maximal eccentric contractions of the elbow flexors with one arm. Whole-body resistance of extracellular and intracellular components (Re and Ri, respectively) on the exercised and non-exercised sides were measured using BIS. Body composition was calculated from both sides of resistance at baseline and 96 h after exercise. Re decreased only on the exercised side at 96 h after exercise (P < 0.05). Fat-free and fat mass values estimated from resistance on the exercised side were altered by 3.1% and - 15.6%, respectively, at 96 h after exercise (P < 0.05); those estimated from the non-exercised side were unaltered. Eccentric exercise-induced muscle damage and inflammation reduce Re and induce non-negligible estimation error in the body composition assessment using BIS.
Assuntos
Composição Corporal/fisiologia , Espectroscopia Dielétrica , Exercício Físico/fisiologia , Inflamação/etiologia , Músculo Esquelético/lesões , Adulto , Humanos , Contração Isométrica , Masculino , Treinamento ResistidoRESUMO
Rheumatoid arthritis (RA) is associated with a wide variety of extra-articular manifestations and comorbidities, several of which can be organ- or even life-threatening. These extra-articular manifestations and comorbidities can also contribute to the physical disability and psychological morbidity of RA that lead to reduced quality of life, higher direct and indirect costs, and societal burden of the disease. Although the expansion of RA treatment options and adoption of treat-to-target approaches has reduced the incidence and severity of several nonarticular manifestations of RA, such as rheumatoid vasculitis and cardiovascular disease events, this does not seem to be shared by all RA comorbidities. Moreover, a number of highly prevalent and impactful RA-driven comorbidities, such as accelerated atherosclerosis, interstitial lung disease, and sarcopenia, can present clinically in the years before the manifestation of joint pain or observable synovitis. A larger proportion of patients with RA have atherosclerosis, myocardial dysfunction, interstitial lung disease, and sarcopenia that is subclinical in the preclinical and earliest clinical phases of RA, emphasizing the importance of targeting the pre-RA phase for the prevention of comorbidities that are often poorly responsive to treatment once they develop. Herein, we review the potential impact of pre-RA prevention on the incidence and burden of extra-articular manifestations and nonarticular comorbidities.
Assuntos
Artrite Reumatoide/fisiopatologia , Comorbidade , Inflamação/fisiopatologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Custos e Análise de Custo , Humanos , Inflamação/etiologia , Prevalência , Prevenção SecundáriaRESUMO
The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally, and internationally. The center has thus far supported a cadre of 6 junior faculty (mentored PIs; mPIs) at a near-R01 level of funding. Two mPIs have graduated by obtaining their independent R01 funding and 3 of the remaining 4 have won significant funding from NIH in the form of R21 and R56 awards. The first year and a half of setting up the center has been punctuated by completion of renovations and acquisition and upgrades for equipment supporting autophagy, inflammation and metabolism studies. The scientific cores usage, and the growth of new studies is promoted through pilot grants and several types of enablement initiatives. The intent to cultivate AIM as a scholarly hub for autophagy and related studies is manifested in its Vibrant Campus Initiative, and the Tuesday AIM Seminar series, as well as by hosting a major scientific event, the 2019 AIM symposium, with nearly one third of the faculty from the International Council of Affiliate Members being present and leading sessions, giving talks, and conducting workshop activities. These and other events are often videostreamed for a worldwide scientific audience, and information about events at AIM and elsewhere are disseminated on Twitter and can be followed on the AIM web site. AIM intends to invigorate research on overlapping areas between autophagy, inflammation and metabolism with a number of new initiatives to promote metabolomic research. With the turnover of mPIs as they obtain their independent funding, new junior faculty are recruited and appointed as mPIs. All these activities are in keeping with AIM's intention to enable the next generation of autophagy researchers and help anchor, disseminate, and convey the depth and excitement of the autophagy field.
Assuntos
Autofagia/fisiologia , Pesquisa Biomédica/organização & administração , Inflamação , Metabolismo/fisiologia , Sociedades Científicas , Pesquisa Biomédica/economia , Pesquisa Biomédica/tendências , Docentes de Medicina/economia , Docentes de Medicina/educação , Financiamento Governamental , Organização do Financiamento/economia , História do Século XXI , Humanos , Inflamação/etiologia , Inflamação/patologia , Mentores , National Institutes of Health (U.S.)/economia , New Mexico , Pesquisadores/economia , Pesquisadores/educação , Sociedades Científicas/economia , Sociedades Científicas/organização & administração , Sociedades Científicas/normas , Sociedades Científicas/tendências , Estados UnidosRESUMO
Background Type-1 diabetes mellitus (T1DM) causes endothelial dysfunction and early atherosclerosis, which can result in premature coronary artery disease. The aim of this study was to determine the impact of glycemic control, vascular oxidative stress and inflammation on vascular health in adolescents with T1DM. Methods This was a cross-sectional study in adolescents with age- and sex-matched T1DM who were ≥12 years and were at least 2 years post-diagnosis. Recruitment was balanced to include individuals with hemoglobin A1c (HbA1c) ≤8.5% (n=27) or with HbA1c ≥9.5% (n=25). Biomarkers of inflammation were measured in the blood including C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), E-selectin, fibrinogen and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and peripheral arterial tonometry (PAT) were assessed. Results Plasma E-selectin level was significantly different between the two groups with higher levels in the group with HbA1c ≥9.5% (65.0±27.7 ng/mL vs. 48.8±21.5 ng/mL, p=0.02). Though cIMT and PAT were not significantly different between the groups, Pearson correlation showed a significant direct relationship between rising HbA1c and mean right cIMT (p=0.02; r=0.37), PAT (p=0.03, r=0.31) and fibrinogen (p=0.03, r=0.03). Conclusions Elevated E-selectin level is an early marker of oxidative stress in T1DM patients with an elevated HbA1c level. Suboptimal glycemic control as evidenced by a rising HbA1c causes early atherosclerosis.
Assuntos
Aterosclerose/diagnóstico , Biomarcadores/análise , Diabetes Mellitus Tipo 1/complicações , Inflamação/diagnóstico , Adolescente , Aterosclerose/sangue , Aterosclerose/etiologia , Proteína C-Reativa/análise , Espessura Intima-Media Carotídea , Estudos Transversais , Selectina E/sangue , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Prognóstico , Fatores de RiscoRESUMO
Bionanocellulose (BNC) is a clear polymer produced by the bacterium Gluconacetobacter xylinus. In our current study, "Research on the use of bacterial nanocellulose (BNC) in regenerative medicine as a function of the biological implants in cardiac and vascular surgery", we carried out material analysis, biochemical analysis, in vitro tests and in vivo animal model testing. In stage 1 of the project, we carried out physical and biological tests of BNC. This allowed us to modify subsequent samples of bacterial bionanocellulose. Finally, we obtained a sample that was accepted for testing on an animal model. That sample we define BNC1. Patches of BNC1 were then implanted into pigs' vessel walls. During the surgical procedures, we evaluated the technical aspects of sewing in the bioimplant, paying special attention to bleeding control and tightness of the suture line and the BNC1 bioimplant itself. We carried out studies evaluating the reaction of an animal body to an implantation of BNC1 into the circulatory system, including the general and local inflammatory reaction to the bioimplant. These studies allowed us to document the potential usefulness of BNC as a biological implant of the circulatory system and allowed for additional modifications of the BNC to improve the properties of this new implantable biological material.