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INTRODUCTION/AIMS: Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. METHODS: Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. RESULTS: None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. DISCUSSION: cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.
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Músculo Esquelético , Distrofia Muscular de Duchenne , Ultrassonografia , Humanos , Feminino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Adulto , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Adulto Jovem , Pessoa de Meia-Idade , Distrofina/genética , Heterozigoto , Adolescente , Força Muscular/fisiologiaRESUMO
A goal of the International Prophylaxis Study Group (IPSG) is to provide an accurate instrument to measure MRI-based disease severity of haemophilic arthropathy at various time points, so that longitudinal changes in disease severity can be identified to support decisions on treatment management. We review and discuss in this paper the evaluative purpose of the IPSG MRI scale in relation to its development and validation processes so far. We also critically appraise the validity, reliability and responsiveness of using the IPSG MRI scale in different clinical and research settings, and whenever applicable, compare these clinimetric properties of the IPSG MRI scale with those of its precursors, the compatible additive and progressive MRI scales.
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Hemartrose/diagnóstico , Hemartrose/prevenção & controle , Artropatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/patologia , Criança , Pré-Escolar , Hemartrose/etiologia , Hemartrose/patologia , Hemofilia A/complicações , Hemofilia A/terapia , Hemossiderina/análise , Humanos , Artropatias/etiologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Membrana Sinovial/metabolismo , Membrana Sinovial/patologiaRESUMO
Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF+ EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity.
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Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.
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Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 ± 0.880 vs 3.254 ± 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings.
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COVID-19 , Heme , Humanos , Biomarcadores , Hemopexina/metabolismo , Pandemias , Gravidade do Paciente , Heme Oxigenase-1/metabolismoRESUMO
Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.
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COVID-19 , Antitrombina III , Antitrombinas , Coagulação Sanguínea , Teste para COVID-19 , Fator Xa , Humanos , Calicreínas/metabolismoRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated. METHODS: A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks. RESULTS: TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041). CONCLUSION: Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. ©2021 ARSAAOA, LLC.
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Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Pólipos Nasais/tratamento farmacológico , Qualidade de Vida , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Tretinoína/efeitos adversosRESUMO
BACKGROUND: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. METHODS: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. RESULTS: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). CONCLUSIONS: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.
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Produtos Finais de Glicação Avançada/metabolismo , Diálise Peritoneal , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Músculos/fisiopatologia , Diálise Renal , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologiaRESUMO
There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.
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Antraciclinas/toxicidade , Antineoplásicos/toxicidade , Ventrículos do Coração/diagnóstico por imagem , Disfunção Ventricular/etiologia , Remodelação Ventricular , Idoso , Cardiotoxicidade , Feminino , Ventrículos do Coração/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular/diagnóstico por imagemRESUMO
INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice. Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events. Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.
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Lúpus Eritematoso Sistêmico/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Neuroimagem/métodos , Autoanticorpos/sangue , Biomarcadores/sangue , Progressão da Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Fatores de RiscoRESUMO
Systemic lupus erythematosus (SLE), presenting with new onset or worsening neuropsychiatric (NP) symptoms, is a challenge in clinical practice. Mimickers such as infections, drug-induced side effects, metabolic abnormalities, malignancies, and alcohol-related disorders have to be excluded, before attributing the manifestations to disease activity. Proper diagnosis is essential to guide adequate management and reduce morbidity and mortality. In this review article, we will highlight clinical, laboratorial, and neuroradiological features that are helpful to assist in the differential diagnosis.
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Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/psicologiaRESUMO
Percutaneous cholecystostomy offers a potentially important type of therapy for critically ill patients with acute cholecystitis who present high risk when undergoing laparotomy or laparoscopy under general anesthesia. It offers a distinct advantage for these kinds of patients by avoiding the risks of the surgical intervention. Percutaneous cholecystostomy is a safe and effective minimally invasive procedure with a high success rate and low procedure-related complications. It should be considered not only in temporary management of calculous cholecystitis, but also in definitive treatment in cases of acalculous cholecystitis.
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Colecistite/terapia , Colecistostomia/métodos , Estado Terminal , Doença Aguda , Humanos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
A colecistostomia percutânea é uma modalidade terapêutica potencialmente importante a ser considerada em pacientes em estado grave com colecistite aguda, que estão sob alto risco ao serem submetidos a laparotomia ou a laparoscopia sob anestesia geral. A colecistostomia pecutânea oferece vantagens neste tipo de paciente por evitar os riscos cirúrgicos da colecistectomia. A colecistostomia percutânea é procedimento seguro, minimamente invasivo e efetivo, com alta taxa de sucesso e com pequeno número de complicações relacionadas ao procedimento. Deve ser considerada não apenas como tratamento temporário da colecistite calculosa, mas também como tratamento definitivo nos casos de colecistite acalculosa.