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The potential clinical usefulness of electron density (ED) imaging, that can be directly estimated using dual-layer spectral computed tomography (CT), has been poorly investigated. We explored whether ED imaging might improve thrombus identification compared to conventional imaging in vitro. We evaluated mechanical thrombectomy material obtained from patients with acute ischemic stroke (AIS) treated in a tertiary level stroke center and immediately fixed in 10% neutral buffered formalin and stored in polystyrene test tubes. The test tubes were immersed in a bucket of water for evaluation by spectral CT, along with scattered control tubes. All images were obtained using a dual-layer detector CT scanner. Each tube was assessed using multiparametric side-by-side view of conventional CT (120 kVp), low monoenergetic imaging (40 keV), and ED images. Fifty-eight polystyrene tubes were analyzed, comprising 52 tubes with thrombectomy material of at least 1 mm2 size obtained from 52 AIS patients, and six control tubes filled with formalin. ED imaging identified accurately the presence of material in all tubes, whereas 2 (3%) of the tubes containing thrombus were not identified by conventional CT, leading to a very good agreement between observers for the presence of material using conventional CT and ED imaging (kappa =0.84, P<0.001). Using ED imaging, thrombus material showed a mean density of 108.8±2.9 percent ED relative to water (%EDW), water had a mean density of 100.0±0.3 %EDW, and formalin a mean density of 103.5±1.2 %EDW. Compared to conventional imaging and 40 keV monoenergetic, ED imaging had a significantly higher signal-to-noise ratio (conventional 10.4±7.0, vs. 40 keV 11.5±8.4, vs. ED 490.0±304.5, P<0.001) and contrast-to-noise ratio (CNR) (conventional 4.3±4.3, vs. 40 keV 5.7±11.2, vs. ED 37.8±29.1, P<0.001). In this in-vitro study, we demonstrated improved visualization of thrombus with ED imaging compared to conventional imaging and low monoenergetic imaging, with a significant increase in CNR.
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PURPOSE: Spectral computed tomography (CT) enables improved tissue characterization, although virtually all research has focused on contrast-enhanced examinations. We hypothesized that changes in myocardial tissue related to acute myocardial infarction (AMI) might potentially be identified without the need for contrast administration using electron density (ED) imaging. PATIENTS AND METHODS: This retrospective observational study involved a small series (n = 15) of patients admitted to our institution with a first AMI without signs of hemodynamic instability and identification of a culprit vessel with invasive coronary angiography during the same admission, who also underwent a noncontrast, low-dose chest CT using a dual-layer spectral CT scanner. Images were assessed in search of dark areas with low density on ED imaging, and the mean percentage ED relative to water (%EDW) was calculated. RESULTS: Using a qualitative approach, ED assessment enabled the identification of 11/15 (73%) affected coronary territories, with a sensitivity of 73% (95% CI: 45; 92%) and a specificity of 87% (95% CI: 69; 96%). AMI segments showed significantly lower ED values than the remote myocardium (103.8 ± 0.8 vs 104.3 ± 0.6 %EDW, P < 0.0001), and a threshold below 103.9 %EDW had a sensitivity of 66% and specificity of 79% for the identification of AMI. In a control group of patients without a history of cardiovascular disease, none had areas with focal reduction of ED following the shape of the myocardial wall. CONCLUSIONS: In our preliminary series, ED imaging showed the potential to enable the identification of myocardial tissue changes related to AMI without iodinated contrast requirement.
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Yodo , Trombosis , Humanos , Tomografía Computarizada por Rayos X/métodos , Medios de ContrasteRESUMEN
BACKGROUND: Hyperacute cardiac imaging of patients with acute ischemic stroke (AIS), though desirable, is impractical. Using delayed-enhancement, low-dose, non-gated, chest spectral computed tomography scans (DESCT), we explored the prevalence and patterns of incidental myocardial late iodine enhancement (LIE) and embolic sources, and their relationship with stroke etiology. METHODS: Since July 2020, DESCT was performed after cerebrovascular CT angiography (CTA) among patients with suspected AIS undergoing CT using a dual-layer spectral scanner, without additional contrast administration. Images were analyzed using monoenergetic reconstructions and iodine density maps, and the myocardial extracellular volume fraction (ECV, %) was calculated. RESULTS: Eighty patients with AIS were included. DESCT identified a cardiac thrombi in 6 patients (7.5%), and a complex aortic plaque in 4 (5%) cases; reclassifying 5 embolic strokes of uncertain source (28% of ESUS) to cardioembolic (CE, n = 3) and non-CE (n = 2) etiologies. LIE was identified in 38 (48%) patients, most commonly (82%) of ischemic pattern. We did not identify significant relationships between AIS etiology and the presence, pattern, and extent of LIE (p > 0.05); ECV (p = 0.56), severe aortic (p = 0.25) or valvular (p = 0.26) disease, or the extent of coronary calcification (p = 0.39). Patients with evidence of major cardiovascular DESCT findings had higher rates of all-cause death at 90 days (42% vs. 19%, p = 0.037). CONCLUSIONS: In this study, hyperacute cardiac imaging of AIS with DESCT identified a high prevalence of incidental cardiac disease predominantly involving LIE of ischemic etiology and mostly not related to the stroke etiology.
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Yodo , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Miocardio , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Tomografía Computarizada por Rayos X/efectos adversos , Tomografía Computarizada por Rayos X/métodosRESUMEN
PURPOSE: We explored epicardial (EAT) and periaortic (PAT) adipose tissue characteristics in patients with acute ischemic stroke (AIS), and the relationship with stroke etiology, calcification burden, and inflammation. METHOD: We included a retrospective cohort of consecutive patients admitted with AIS between 2015 and 2020 who underwent a chest computed tomography. We calculated volumes and attenuation of EAT and PAT, and coronary artery (CAC), and thoracic aortic (TAC) calcification. Admission's neutrophil/lymphocyte ratio (NLR) was recorded. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS), and patients were discriminated between cardioembolic (CE), non-CE, and embolic strokes of uncertain source (ESUS). RESULTS: A total of 182 patients were included. EAT (non-CE 127.4 ± 47.1 cm3; CE 133.3 ± 56.7 cm3; ESUS 121.6 ± 63.5 cm3, p > 0.05) and PAT (non-CE 37.4 ± 18.6 cm3; CE 40.4 ± 17.2 cm3; ESUS 34.5 ± 14.1 cm3, p > 0.05) volumes were similar between stroke etiologies. Patients with CE stroke had higher PAT attenuation (PAT = non-CE -84.4 ± 7.0 HU; CE -78.1 ± 9.9 HU; ESUS -82.3 ± 9.3 HU, p < 0.001). Using multiple linear regression, albeit weak, we found a significant relationship between NLR and PAT attenuation [Beta 0.24; (95% CI 0.04-0.51), p < 0.05). Despite similar volume, PAT attenuation was higher (p < 0.01) among demised patients. CONCLUSION: In this study, we identified higher periaortic fat attenuation, despite similar fat volume, in patients with CE stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Tejido Adiposo/diagnóstico por imagen , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Humanos , Pericardio , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND: Systolic dysfunction in pectus excavatum (PEX) is usually very subtle and mainly focused on the right ventricle (RV), leading to normal or unremarkable cardiac imaging findings unless involving exercise stress. OBJECTIVES: We evaluated systolic function in PEX using longitudinal strain cardiac magnetic resonance (CMR), a validated parameter for the assessment of the systolic deformation of subendocardial fibers. METHODS: This prospective registry comprised consecutive patients with PEX who were referred to CMR to define treatment strategies or to establish surgical candidacy. We also included a control group of 15 healthy volunteers without chest wall abnormalities. Using dedicated software, we evaluated the endocardial global longitudinal strain (GLS) of both ventricles and the endocardial global circumferential strain (GCS) of the left ventricle (LV). RESULTS: A total of 50 patients with PEX comprised the study population, with a mean age of 19.9 ± 8.0 years. The right ventricular ejection fraction (RVEF) of patients with PEX was significantly lower compared to the control group both at end-expiration (59.5 ± 6.8 vs. 64.7 ± 4.7%, p = 0.008) and end-inspiration (56.7 ± 7.2%, vs. 62.7 ± 4.4, p = 0.004); as well as the pulmonary stroke distance (12.6 ± 2.5, vs. 15.0 ± 2.0 cm, p = 0.001). The LV volumetric analysis revealed no differences between PEX and the control group (p > 0.05 for all) regardless of the respiratory cycle, with a mean expiratory LV ejection fraction (LVEF) of 61.4 ± 6.0%. In contrast, the GLS of the LV was significantly lower in PEX compared to controls (-21.2 ± 3.2 vs. -23.7 ± 3.0%, p = 0.010), whereas GCS was similar either at expiration (-28.5 ± 4.0%, vs. -29.5 ± 2.8, p = 0.38) or inspiration (-29.3 ± 4.1%, vs.-28.9 ± 2.3, p = 0.73). CONCLUSIONS: In this study, we demonstrated that longitudinal strain analysis might enable the detection of very subtle left ventricular systolic function abnormalities in patients with PEX, that are commonly overlooked using the conventional assessment. LEVEL OF EVIDENCE: II.
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Tórax en Embudo , Cardiopatías Congénitas , Disfunción Ventricular Izquierda , Adolescente , Adulto , Niño , Tórax en Embudo/complicaciones , Tórax en Embudo/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Espectroscopía de Resonancia Magnética , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/patología , Función Ventricular Derecha , Adulto JovenRESUMEN
BACKGROUND: Collective risk factors such as climate and pollution impact on the risk of acute cardiovascular events, including ST-elevation myocardial infarction (STEMI). There is limited data however on the precise temporal and independent association between these factors and STEMI, and the potentially interacting role of government policies against Coronavirus disease 2019 (COVID-19), especially for Latin America. METHODS: We retrospectively collected aggregate data on daily STEMI admissions at 10 tertiary care centers in the Buenos Aires metropolitan area, Argentina, from January 1, 2017 to November 30, 2020. Daily measurements for temperature, humidity, atmospheric pressure, wind direction, wind speed, and rainfall, as well as carbon monoxide (CO), nitrogen dioxide, and particulate matter <10 µm (PM10), were retrieved. Exploratory analyses focused on key COVID-19-related periods (e.g. first case, first lockdown), and Stringency Index quantifying the intensity of government policy response against COVID-19. RESULTS: A total of 1498 STEMI occurred over 1430 days, for an average of 0.12 STEMI per center (decreasing from 0.130 in 2018 to 0.102 in 2020, P=0.016). Time series analysis showed that lower temperature and higher concentration of CO and PM10 were all significantly associated with an increased rate of STEMI (all P<0.05), whereas COVID-19 outbreak, lockdown, and stringency of government policies were all inversely associated with STEMI (all P<0.05). Notably, environmental features impacted as early as 28 days before the event (all P<0.05), even if same or prior day associations proved stronger (all P<0.05). Multivariable analysis suggested that maximum temperature (P=0.001) and PM10 (P=0.033) were the strongest predictor of STEMI, even after accounting for COVID-19-related countermeasures (P=0.043). CONCLUSIONS: Lower temperature and higher concentrations of CO and PM10 are associated with significant increases in the rate of STEMI in a large Latin American metropolitan area. The reduction in STEMI cases seen during the COVID-19 pandemic is at least in part mediated by improvements in pollution, especially reductions in PM10.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Infarto del Miocardio con Elevación del ST , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , COVID-19/epidemiología , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/inducido químicamente , Estudios Retrospectivos , Pandemias , Control de Enfermedades Transmisibles , Material ParticuladoRESUMEN
RESUMEN Introducción: El score de calcio coronario (SCC) es una herramienta de prevención subutilizada, en parte debido a su elevado costo, que no debería diferir del de una tomografía computarizada (TC) de tórax. El SCC puede ser evaluado mediante una TC de tórax convencional, generalmente utilizando escalas visuales o semicuantitativas, y con valor pronóstico similar al gatillado. Material y métodos: En este estudio observacional retrospectivo, incluimos pacientes (n = 35) en quienes se realizó dentro de la misma internación una TC de tórax no gatillada de baja dosis y un SCC gatillado. Resultados: Identificamos una buena concordancia entre los métodos tanto en su valoración cualitativa como cuantitativa, con una media de 3,86 ± 0,7 segmentos con calcificaciones arteriales coronarias mediante SCC gatillado, comparado con 3,79 ± 0,6 segmentos mediante TC de tórax no gatillada de baja dosis (coeficiente de correlación de concordancia 0,98 [IC 95% 0,95-0,99]) y una subestimación del SCC evaluado mediante unidades Agatston del 9,8 %. Conclusión: En este estudio, demostramos que el SCC podría ser evaluado con precisión de forma tanto cualitativa como cuantitativa mediante estudios de TC de tórax no gatillada de baja dosis.
ABSTRACT Background: Coronary calcium scoring (CCS) is an underused prevention tool, possibly due to its high cost, which should not differ from a chest computed tomography (CT) scan. CCS can be assessed using conventional chest CT, generally through a visual or semiquantitative approach, and with a similar prognostic value compared to ECG-gated CCS. Methods: In this retrospective observational study, we included patients (n = 35) who underwent a low-dose non-gated chest CT (LDCT) and an ECG-gated CCS within the same hospitalization. Results: We identified a good agreement between techniques both in their qualitative and quantitative assessment, with a mean of 3.86 ± 0.7 segments with calcifications by ECG-gated compared to 3.79 ± 0.6 segments by LDCT (concordance correlation coefficient 0.98 (95% CI 0.95-0.99), and a 9.8% underestimation of the Agatston score. Conclusions: In this study, we showed that the CCS might be accurately assessed both qualitatively and quantitatively by LDCT studies.
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The complex and reciprocal relationship between the brain and the heart has gained increasing attention under the concept of neurocardiology. Myocardial injury is common in cerebrovascular disease, and cardiovascular complications are the second leading cause of death after stroke. Cardiac computed tomography (CT) is a fast and reliable non-invasive tool for the assessment of cardioembolic sources. Compared to single energy CT, spectral/dual energy cardiac CT improves tissue characterization and also leads to significant reductions in contrast volume. In this review article, we portray the potential clinical applications of spectral CT in neurocardiology, focusing in the enhanced diagnosis of cardioembolic sources and cardiovascular risk assessment of patients with stroke, including improved detection of thrombus, identification of subtle myocardial disease, and pulmonary complications within the same session.
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Cardiopatías , Accidente Cerebrovascular , Trombosis , Corazón , Cardiopatías/diagnóstico por imagen , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Tomografía Computarizada por Rayos XRESUMEN
Neisseria meningitidis is a strictly human pathogen and is the major cause of septicemia and meningitis worldwide. Factor H binding protein (fHbp) is a meningococcal surface-exposed lipoprotein that binds the human Complement factor H allowing the bacterium to evade the host innate immune response. FHbp is also a key antigen in two vaccines against N. meningitidis serogroup B. Although the fHbp gene is present in most circulating meningococcal strains, level of fHbp expression varies among isolates and has been correlated to differences in promoter sequences upstream of the gene. Here we elucidated the sequence determinants that control fHbp expression in globally circulating strains. We analyzed the upstream fHbp intergenic region (fIR) of more than 5800 strains representative of the UK circulating isolates and we identified eleven fIR sequence alleles which represent 88% of meningococcal strains. By engineering isogenic recombinant strains where fHbp expression was under the control of each of the eleven fIR alleles, we confirmed that the fIR sequence determines a specific and distinct level of expression. Moreover, we identified the molecular basis for variation in expression through polymorphisms within key regulatory regions that are known to affect fHbp expression. We experimentally established three expression groups, high-medium-low, that correlated directly with the susceptibility to killing mediated by anti-fHbp antibodies and the ability of the meningococcal strain to survive within human serum. By using this sequence classification and information about the variant, we predicted fHbp expression in the panel of UK strains and we observed that strains with higher expressing fIR alleles are more likely associated with invasive disease. Overall, our findings can contribute to understand and predict vaccine coverage mediated by fHbp as well as to shed light on the role of this virulence factor in determining an invasive phenotype.
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Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Infecciones Meningocócicas/genética , Neisseria meningitidis/genética , Humanos , Vacunas Meningococicas , Polimorfismo GenéticoRESUMEN
The use of colchicine is associated with a significant reduction of cardiac adverse events in patients with coronary artery disease. Past small randomized trials with oral immunosuppressive or anti-inflammatory therapies have demonstrated a reduction of adverse clinical events after bare metal stent implantation. The potential role of adjunctive colchicine after bare-metal stent implantation, compared with drug-eluting stent alone, is unknown. The primary end point of the study will be to compare cost-effectiveness at 1 year of follow-up of coronary intervention with bare-metal stent implantation plus 1 mg of colchicine during 3 months versus percutaneous coronary intervention with drug-eluting stent implantation alone. ClinicalTrials.gov identifier: NCT04382443.
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Reestenosis Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Colchicina/efectos adversos , Angiografía Coronaria , Humanos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Stents , Resultado del TratamientoRESUMEN
The classical complement pathway is triggered when antigen-bound immunoglobulins bind to C1q through their Fc region. While C1q binds to a single Fc with low affinity, a higher avidity stable binding of two or more of C1q globular heads initiates the downstream reactions of the complement cascade ultimately resulting in bacteriolysis. Synergistic bactericidal activity has been demonstrated when monoclonal antibodies recognize nonoverlapping epitopes of the same antigen. The aim of the present work was to investigate the synergistic effect between antibodies directed toward different antigens. To this purpose, we investigated the bactericidal activity induced by combinations of monoclonal antibodies (mAbs) raised against factor H-binding protein (fHbp) and Neisserial Heparin-Binding Antigen (NHBA), two major antigens included in Bexsero, the vaccine against Meningococcus B, for prevention from this devastating disease in infants and adolescents. Collectively, our results show that mAbs recognizing different antigens can synergistically activate complement even when each single Mab is not bactericidal, reinforcing the evidence that cooperative immunity induced by antigen combinations can represent a remarkable added value of multicomponent vaccines. Our study also shows that the synergistic effect of antibodies is modulated by the nature of the respective epitopes, as well as by the antigen density on the bacterial cell surface.
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Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Proteínas del Sistema Complemento/inmunología , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Bacterianas/inmunología , Proteínas Portadoras/inmunología , Factor H de Complemento/inmunología , Epítopos/inmunología , Neisseria meningitidis/inmunología , Determinación de Anticuerpos Séricos Bactericidas/métodosRESUMEN
PURPOSE: To evaluate the epidemiology of diabetes and quality of care of institutionalized patients with diabetes in Italian nursing homes. More specifically, to evaluate the adherence to the national/international guidelines for the management of older people with diabetes. METHODS: Data related to the epidemiology of diabetes and the quality of care were collected from questionnaires sent to 41 nursing homes. Data were extracted from papers, electronic medical records and validated operating protocols regulating the management of patients with diabetes in various homes. Completed questionnaires were returned in electronic format and centrally processed. RESULTS: Out of 4692 residents, 906 (19.3%) had diabetes. Among these residents, excluding patients undergoing diet treatment, more than half were on insulin treatment (alone or in combination with oral antidiabetic agents). The critical findings can be summarized as follows: a lack of shared diagnostic-therapeutic protocols, specifically related to evaluation of frailty; the preparation of nutritional and physical activity plans; the clarification of the objectives of the treatment; the timing of insulin administration (frequent use of sliding scale); the frequency and timing of capillary blood glucose; metabolic control methods; hypoglycemia and hyperglycemia treatment; and the scant use of new drugs that do not cause hypoglycemia. CONCLUSION: Our data revealed substantial heterogeneity in the treatment of nursing home residents with diabetes in Italy with many discrepancies between what is recommended in the guidelines and real-world practice. The implementation of local diagnostic-therapeutic protocols shared by all caregivers should be encouraged and properly funded to overcome communication problems between doctors and nurses and eventually improve the quality of care for institutionalized patients with diabetes.
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Diabetes Mellitus , Calidad de la Atención de Salud , Anciano , Diabetes Mellitus/terapia , Humanos , Hipoglucemiantes , Italia , Casas de SaludRESUMEN
PURPOSE: The aim of the paper is to evaluate if advanced dMRI techniques, including diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI), could provide novel insights into the subtle microarchitectural modifications occurring in the corticospinal tract (CST) of stroke patients in subacute and chronic phases. METHODS: Seventeen subjects (age 68 ± 11 years) in the subacute phase (14 ± 3 days post-stroke), 10 of whom rescanned in the chronic phase (231 ± 36 days post-stroke), were enrolled. Images were acquired using a 3-T MRI scanner with a two-shell EPI protocol (20 gradient directions, b = 700 s/mm2, 3 b = 0; 64 gradient directions, b = 2000 s/mm2, 9 b = 0). DTI-, DKI-, and NODDI-derived parameters were calculated in the posterior limb of the internal capsule (PLIC) and in the cerebral peduncle (CP). RESULTS: In the subacute phase, a reduction of FA, AD, and KA values was correlated with an increase of ODI, RD, and AK parameters, in both the ipsilesional PLIC and CP, suggesting that increased fiber dispersion can be the main structural factor. In the chronic phase, a reduction of FA and an increase of ODI persisted in the ipsilesional areas. This was associated with reduced Fic and increased MD, with a concomitant reduction of MK and increase of RD, suggesting that fiber reduction, possibly due to nerve degeneration, could play an important role. CONCLUSIONS: This study shows that advanced dMRI approaches can help elucidate the underpinning architectural modifications occurring in the CST after stroke. Further follow-up studies on bigger cohorts are needed to evaluate if DKI- and NODDI-derived parameters might be proposed as complementary biomarkers of brain microstructural alterations.
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Isquemia Encefálica/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador , Tractos Piramidales/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Isquemia Encefálica/complicaciones , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
Stroke is one of the main causes of death, neurological dysfunctions or disability in elderly. Neuroprotective drugs have been proposed to improve long-term recovery after stroke, but failed to reach clinical effectiveness. Hence, recent studies suggested that restorative therapies should combine neuroprotection and remyelination. Montelukast, an anti-asthmatic drug, was shown to exert neuroprotection in animal models of CNS injuries, but its ability to affect oligodendrocytes, restoring fiber connectivity, remains to be determined. In this study, we evaluated whether montelukast induces long-term repair by promoting fiber connectivity up to 8 weeks after middle cerebral artery occlusion (MCAo), using different experimental approaches such as in vivo diffusion magnetic resonance imaging (MRI), electrophysiological techniques, ex vivo diffusion tensor imaging (DTI)-based fiber tracking and immunohistochemistry. We found that, in parallel with a reduced evolution of ischemic lesion and atrophy, montelukast increased the DTI-derived axial diffusivity and number of myelin fibers, the density of myelin binding protein (MBP) and the number of GSTpi+ mature oligodendrocytes. Together with the rescue of MCAo-induced impairments of local field potentials in ischemic cortex, the data suggest that montelukast may improve fibers reorganization. Thus, to ascertain whether this effect involved changes of oligodendrocyte precursor cells (OPCs) activation and maturation, we used the reporter GPR17iCreERT2:CAG-eGreen florescent protein (GFP) mice that allowed us to trace the fate of OPCs throughout animal's life. Our results showed that montelukast enhanced the OPC recruitment and proliferation at acute phase, and increased their differentiation to mature oligodendrocytes at chronic phase after MCAo. Considering the crosstalk between OPCs and microglia has been widely reported in the context of demyelinating insults, we also assessed microglia activation. We observed that montelukast influenced the phenotype of microglial cells, increasing the number of M2 polarized microglia/macrophages, over the M1 phenotype, at acute phase after MCAo. In conclusion, we demonstrated that montelukast improves fiber re-organization and long-term functional recovery after brain ischemia, enhancing recruitment and maturation of OPCs. The present data suggest that montelukast, an already approved drug, could be "repositioned "as a protective drug in stroke acting also on fiber re-organization.
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Acetatos/uso terapéutico , Antiasmáticos/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Quinolinas/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/patología , Ciclopropanos , Infarto de la Arteria Cerebral Media/fisiopatología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Microglía/efectos de los fármacos , Accidente Cerebrovascular/fisiopatología , SulfurosRESUMEN
BACKGROUND: Although antitumor necrosis factor alfa (TNFα) agents are widely used to treat patients with inflammatory bowel diseases (IBD) - both Crohn's disease (CD) and ulcerative colitis (UC) - there is still some uncertainty in the cell type expressing TNFα in human ileo-colonic segments. AIMS: We investigated the immunohistochemical (IHC) expression of TNFα in the ileo-colonic segments of patients with both active CD and UC, to establish its anatomic and cellular localization in the inflamed sites. Our aim was to identify patients potentially resistant to anti TNFα agents. PATIENTS AND METHODS: Ileo-colonic slides of complete histological mapping of patients with CD and UC before any treatment was started were obtained, and serial sections assessed for TNFα expression, together with IHC markers for lymphocytes, macrophages, and plasma cells. RESULTS: TNFα was expressed in almost all inflamed segments of IBD patients, albeit with different strength, and was present, in addition to lymphocytes and, to a lesser extent, to macrophages, in plasma cells, where it had a strong positivity, as also demonstrated by colocalization of specific IHC staining. The expression of TNFα was mostly focal in CD patients and more diffuse in UC patients, likely due to the different patterns of inflammation (transmural and mucosal) of the two entities. CONCLUSIONS: In IBD, TNFα is strongly expressed also in plasma cells, and it is easily evidenced by conventional IHC techniques. It remains to be established whether this observation might be useful in future to establish in routine biopsy samples whether patients may be responsive to treatments toward this cytokine.
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Enfermedades Inflamatorias del Intestino/metabolismo , Células Plasmáticas/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Biopsia , Colon/metabolismo , Femenino , Humanos , Íleon/metabolismo , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Insulin injection aspects, such as fear of injection and pain, directly affect glycemic control, patient adherence and quality of life. Use of thinner and shorter needles could increase acceptance of injections. The aim of the study is to evaluate the non-inferiority of the new 34G × 3.5 mm needle compared to a 32G × 4 mm in patients with diabetes treated with insulin. METHODS: This is an open, randomized, two-period crossover, non-inferiority trial. Every treatment period lasted 3 weeks. Patients with type 1 or type 2 diabetes, treated with multiple daily insulin injections, were randomly assigned to receive a 34G × 3.5 mm or a 32G × 4 mm pen needle. The primary endpoint was the non-inferiority of the 34G × 3.5 mm in comparison with the 32G × 4 mm pen needle in terms of percentage absolute change of blood fructosamine (% |ΔFru|), using a non-inferiority margin of 20%. RESULTS: Overall 77 patients were randomized and 73 completed the study. Patients characteristics were: 52% male, 80.5% affected by type 1 diabetes, mean age 52 years (±14.6), mean BMI 24.5 kg/m2 (±5.6), HbA1c 8% (±1.1) and baseline fructosamine level 350 µmol/l (±84). Mean fructosamine levels increased by 0.56 µmol/l with the 34G needle, while a reduction of 7.29 µmol/l was documented with the 32G needle. The difference between the two groups (7.84 µmol/l) was not statistically significant (p = .27). The % |ΔFru| between the two groups was 7.55% (95% CI 5.67-9.44), meeting the non-inferiority criterion. Glycemic variability, expressed as standard deviation of fasting blood glucose and post-prandial glucose, was not different between the two treatment groups (p = .63 and p = .77, respectively). CONCLUSIONS: The 34G × 3.5 mm needle was non-inferior to the 32G × 4 mm needle regarding fructosamine levels and glycemic variability supporting the suitability of the 34G × 3.5 mm needle for insulin injection in patients with diabetes. CLINICAL TRIAL REGISTRATION: NCT02690467.