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1.
J Stroke Cerebrovasc Dis ; 32(2): 106936, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36516592

RESUMEN

OBJECTIVES: To evaluate the value of an extended emergency computed tomography angiography (CTA) including cardiac imaging in patients with acute ischemic stroke for the detection of left atrial appendage (LAA) thrombus compared to transesophageal echocardiography (TEE) as a reference standard. MATERIALS AND METHODS: We conducted a retrospective case-control study of patients with presumed acute ischemic stroke who had undergone non-ECG-gated CTA for the craniocervical vessels with an extended coverage including the heart in the context of emergency stroke evaluation and for whom TEE was available as part of the routine stroke diagnostic. We selected cases with evidence of LAA thrombus in TEE and controls without LAA thrombus in TEE in a 1:3 ratio. Two independent observers analyzed CTA images for presence of LAA thrombus and were blinded to the presence of thrombus in TEE. RESULTS: Twenty-two patients with LAA thrombus in TEE, and 66 patients without LAA thrombus in TEE were included. The detection of LAA thrombus using CTA showed a sensitivity of 63.6%, a specificity of 81.8%, a positive predictive value of 53.9% and a negative predicted value of 87.1%. Interobserver agreement was only moderate (Cohen´s κ = 0.43). CONCLUSIONS: An extended emergency CTA including cardiac imaging can be helpful in early risk stratification in patients with stroke of cardioembolic origin. However, our data show that a standard CTA of craniocervical vessels with extended coverage of the heart is of limited value when compared to TEE, the standard method of detecting LAA thrombi.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Cardiopatías , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Angiografía por Tomografía Computarizada , Ecocardiografía Transesofágica/métodos , Apéndice Atrial/diagnóstico por imagen , Estudios Retrospectivos , Estudios de Casos y Controles , Cardiopatías/diagnóstico , Trombosis/complicaciones , Trombosis/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen
2.
Kidney Int ; 100(6): 1303-1315, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34352311

RESUMEN

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Apolipoproteína L1/genética , Humanos , Riñón , Estudios Retrospectivos , SARS-CoV-2
3.
4.
PLoS Biol ; 14(8): e1002526, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27500644

RESUMEN

It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respond, expand, and differentiate into memory-like cells in a ligand-specific manner. MHC I-binding inhibitory receptors, including those belonging to the Ly49 and KIR families, are expressed in a variegated manner, which creates ligand-specific diversity within the NK cell pool. However, how NK cells determine which inhibitory receptors to express on their cell surface during a narrow window of development is largely unknown. In this manuscript, we demonstrate that signals from activating receptors are critical for induction of Ly49 and KIR receptors during NK cell development; activating receptor-derived signals increased the probability of the Ly49 bidirectional Pro1 promoter to transcribe in the forward versus the reverse direction, leading to stable expression of Ly49 receptors in mature NK cells. Our data support a model where the balance of activating and inhibitory receptor signaling in NK cells selects for the induction of appropriate inhibitory receptors during development, which NK cells use to create a diverse pool of ligand-specific NK cells.


Asunto(s)
Células Asesinas Naturales/inmunología , Subfamilia A de Receptores Similares a Lectina de Células NK/inmunología , Receptores KIR/inmunología , Transducción de Señal/inmunología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Células Cultivadas , Citometría de Flujo , Variación Genética/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Células Asesinas Naturales/metabolismo , Ligandos , Ratones Endogámicos C57BL , Ratones Noqueados , Subfamilia A de Receptores Similares a Lectina de Células NK/genética , Subfamilia A de Receptores Similares a Lectina de Células NK/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/inmunología , Fosfoproteínas/metabolismo , Interferencia de ARN , Receptores KIR/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética
5.
Eur Radiol ; 28(12): 4949-4958, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29948072

RESUMEN

OBJECTIVES: The pathogenesis leading to poor functional outcome after aneurysmal subarachnoid haemorrhage (aSAH) is multifactorial and not fully understood. We evaluated a machine learning approach based on easily determinable clinical and CT perfusion (CTP) features in the course of patient admission to predict the functional outcome 6 months after ictus. METHODS: Out of 630 consecutive subarachnoid haemorrhage patients (2008-2015), 147 (mean age 54.3, 66.7% women) were retrospectively included (Inclusion: aSAH, admission within 24 h of ictus, CTP within 24 h of admission, documented modified Rankin scale (mRS) grades after 6 months. Exclusion: occlusive therapy before first CTP, previous aSAH, CTP not evaluable). A random forests model with conditional inference trees was optimised and trained on sex, age, World Federation of Neurosurgical Societies (WFNS) and modified Fisher grades, aneurysm in anterior vs. posterior circulation, early external ventricular drainage (EVD), as well as MTT and Tmax maximum, mean, standard deviation (SD), range, 75th quartile and interquartile range to predict dichotomised mRS (≤ 2; > 2). Performance was assessed using the balanced accuracy over the training and validation folds using 20 repeats of 10-fold cross-validation. RESULTS: In the final model, using 200 trees and the synthetic minority oversampling technique, median balanced accuracy was 84.4% (SD 0.7) over the training folds and 70.9% (SD 1.2) over the validation folds. The five most important features were the modified Fisher grade, age, MTT range, WFNS and early EVD. CONCLUSIONS: A random forests model trained on easily determinable features in the course of patient admission can predict the functional outcome 6 months after aSAH with considerable accuracy. KEY POINTS: • Features determinable in the course of admission of a patient with aneurysmal subarachnoid haemorrhage (aSAH) can predict the functional outcome 6 months after the occurrence of aSAH. • The top five predictive features were the modified Fisher grade, age, the mean transit time (MTT) range from computed tomography perfusion (CTP), the WFNS grade and the early necessity for an external ventricular drainage (EVD). • The range between the minimum and the maximum MTT may prove to be a valuable biomarker for detrimental functional outcome.


Asunto(s)
Aneurisma Intracraneal , Hemorragia Subaracnoidea , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/fisiopatología , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/fisiopatología
6.
J Neuroradiol ; 44(6): 371-376, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28687123

RESUMEN

BACKGROUND AND PURPOSE: The pathogenesis of poor functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) is not fully understood. Microcirculatory dysfunction, which can be indirectly measured by CT perfusion (CTP), is assumed to play a central role. We evaluated the predictive value of early changes in microcirculation for secondary critical perfusion changes. MATERIALS AND METHODS: Out of 351 consecutive aSAH patients, 166 patients with ≥1 CTP within 72h of ictus (early CTP) and ≥3 CTPs in total were included in the retrospective analysis (53.2±12.4years of age). Receiver-operating-characteristic (ROC) analysis was performed to identify the mean transit time (MTT) threshold in early CTP with the highest sensitivity and specificity for predicting secondary critical perfusion changes >72h after ictus. The odds ratio was calculated and the threshold for the highest odds ratio was determined. RESULTS: Secondary critical perfusion changes were observed in 67/166 patients (40.4%). An early MTT 1.3 times the mean normal MTT could predict those changes with an odds ratio of 2.67 (sensitivity 67.2%, specificity 56.6%). Shifting the threshold to 1.26 times the mean normal MTT resulted in an odds ratio of 3.56 (sensitivity 79.1%, specificity 48.5%). CONCLUSIONS: Early MTT is predictive of secondary critical perfusion changes, which could have applications for neuromonitoring and treatment.


Asunto(s)
Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Microcirculación , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Circulación Cerebrovascular , Medios de Contraste , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad
7.
Blood ; 121(16): 3135-46, 2013 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-23407547

RESUMEN

Signaling pathways leading to natural killer (NK)-cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating receptors. We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is recruited to microclusters at the plasma membrane in activated NK cells and that this is required for initiation of downstream signaling and multiple NK-cell effector functions in vitro and in vivo. Surprisingly, we found that 2 types of proximal signaling complexes involving SLP-76 were formed. In addition to the canonical membrane complex formed between SLP-76 and linker for activation of T cells (LAT) family members, a novel LAT family-independent SLP-76-dependent signaling pathway was identified. The LAT family-independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-promoting adaptor protein (ADAP). Both the LAT family-dependent and ADAP-dependent pathway contributed to interferon-gamma production and cytotoxicity; however, they were not essential for other SLP-76-dependent events, including phosphorylation of AKT and extracellular signal-related kinase and cellular proliferation. These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/inmunología , Sistema de Transporte de Aminoácidos y+/inmunología , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/inmunología , Células Asesinas Naturales/inmunología , Subfamilia A de Receptores Similares a Lectina de Células NK/inmunología , Fosfoproteínas/inmunología , Proteínas Adaptadoras Transductoras de Señales/análisis , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Sistema de Transporte de Aminoácidos y+L , Animales , Línea Celular Tumoral , Proliferación Celular , Células Cultivadas , Interferón gamma/inmunología , Células Asesinas Naturales/citología , Células Asesinas Naturales/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Fosfoproteínas/análisis , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal
8.
Lab Anim ; 58(1): 65-72, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37698341

RESUMEN

Minipigs are used as in vivo endovascular models, particularly in stroke and aneurysm research. However, detailed knowledge of the diameters of forelimb arteries that are commonly used as surrogates for human brain-supplying arteries are lacking. This study aimed to determine the diameters of forelimb and neck arteries in Aachen minipigs and to compare those to the diameters of human cerebral brain-supplying arteries in order to assess the validity of the Aachen minipig as a human intracranial in vivo model. We measured the diameters in the external carotid artery and eight different branches of the subclavian artery in 12 Aachen minipigs using angiographic imaging. Analysed arteries comprised the external carotid artery, axillary artery, brachial artery, subscapular artery first segment, subscapular artery second segment, external thoracic artery, caudal circumflex humeral artery, suprascapular artery and thoracodorsal artery. We compared these diameters to diameters of the following human brain-supplying arteries: terminal internal carotid artery (carotid-T and petrous segment), M1 segment of the middle cerebral artery, M2 segments of the middle cerebral artery, anterior cerebral artery, vertebral artery and basilar artery. Median diameters of porcine forelimb arteries ranged from 1.8 to 4.9 mm, and human brain supplying arteries ranged in diameter from 1.4 to 4.3 mm. Depending on the intended use, this allows porcine forelimb arteries to be selected which are statistically comparable to human brain-supplying vessels. In conclusion, we identified several equivalent arteries of the porcine subclavian branches that are comparable to human brain-supplying arteries. This may help to validate the minipig as a suitable in vivo model for neurovascular experiments.


Asunto(s)
Arterias Carótidas , Humanos , Animales , Porcinos , Porcinos Enanos
9.
Neuroradiology ; 55(11): 1323-31, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24026709

RESUMEN

INTRODUCTION: Dynamic perfusion computed tomography (PCT) has been established as a diagnostic instrument for the detection of vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to assess the prognostic impact of PCT parameters after SAH on the long-term outcome of patients. METHODS: Three hundred twelve patients were retrospectively interrogated with a questionnaire 23.06 ± 14.33 months after spontaneous subarachnoid hemorrhage. The modified Rankin scale (mRS) was determined, respectively. Scheduled PCT data sets from the first days after ictus were available for all patients. RESULTS: The maximum mean transit time over several examinations per hemisphere (MTTPEAK) values were significantly correlated (p ≤ 0.001, r = 0.422) with the clinical long-term outcome (mRS). Corresponding to our linear regression analysis, MTTPEAK is the second most important regressor (behind clinical severity of the initial hemorrhage) for the prediction of long-term mRS. An MTTPEAK threshold of 3.98 s (identified by receiver operating characteristic analysis, area under the curve = 0.75) predicted an unfavorable long-term outcome (mRS ≥ 2) with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 67.3, 74.3, 84.5, 52.1, and 69.6 %, respectively. CONCLUSION: The presented data corroborate the relevance of PCT data for the clinical long-term outcome of SAH patients. By identification of patients who are at risk for a bad outcome and may need escalation of therapy, risk-benefit analysis is supported.


Asunto(s)
Imagen de Perfusión/métodos , Imagen de Perfusión/estadística & datos numéricos , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Femenino , Alemania , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Hemorragia Subaracnoidea/terapia , Resultado del Tratamiento
10.
Anal Chim Acta ; 1239: 340700, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36628710

RESUMEN

The behaviour and distribution of iodine in the environment are of significant interest in a range of scientific disciplines, from health, as iodine is an essential element for humans and animals, to climate and air quality, to geochemistry. Aquatic environments are the reservoir for iodine, where it exists in low concentrations as iodide, iodate and dissolved organic iodine and in which it undergoes redox reactions. The current measurement techniques for iodine species are typically time-consuming, subject to relatively poor precision and require specialist instrumentation including those that require mercury as an electrode. We present a new method for measuring iodine species, that is tailored towards lower dissolved organic carbon waters, such as seawater, rainwater and snow, using ion exchange chromatography (IC) with direct ultra-violet spectrophotometric detection of iodide and without the need for sample pre-concentration. Simple chemical amendments to the sample allow for the quantification of both iodate and dissolved organic iodine in addition to iodide. The developed IC method, which takes 16 min, was applied to contrasting samples that encompass a wide range of aqueous environments, from Arctic sea-ice snow (low concentrations) to coastal seawater (complex sample matrix). Linear calibrations are demonstrated for all matrices, using gravimetrically prepared potassium iodide standards. The detection limit for the iodide ion is 0.12 nM based on the standard deviation of the blank, while sample reproducibility is typically <2% at >8 nM and ∼4% at <8 nM. Since there is no environmental certified reference material for iodine species, the measurements made on seawater samples using this IC method were compared to those obtained using established analytical techniques; iodide voltammetry and iodate spectrophotometry. We calculated recoveries of 102 ± 16% (n = 107) for iodide and 116 ± 9% (n = 103) for iodate, the latter difference may be due to an underestimation of iodate by the spectrophotometric method. We further compared a chemical oxidation and reduction of the sample to an ultra-violet digestion to establish the total dissolved iodine content, the average recovery following chemical amendments was 98 ± 4% (n = 92). The new method represents a simple, efficient, green, precise and sensitive method for measuring dissolved speciated iodine in complex matrices.


Asunto(s)
Yodo , Animales , Humanos , Yodo/análisis , Yoduros/análisis , Yodatos/análisis , Nieve , Reproducibilidad de los Resultados , Agua de Mar/química , Espectrofotometría , Cromatografía por Intercambio Iónico
11.
Cancers (Basel) ; 15(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37686623

RESUMEN

Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. Obesity is a growing public health threat and a risk factor for multiple myeloma, although the mechanisms by which obesity contributes to MM growth and progression have not been fully elucidated. In the present study, we evaluated whether crosstalk between adipocytes and MM cells promoted drug resistance and whether this was amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen normal (BMI = 20-25 kg/m2), overweight (25-30 kg/m2), or obese (30-35 kg/m2) patients undergoing elective liposuction were utilized. Cells were differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple myeloma cell lines, and treated with standard MM therapies, including bortezomib or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found that adipocytes from overweight and obese individuals increased cell adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 activity, and protected MM cells from drug-induced decreases in viability. In summary, we provide an underlying mechanism by which obesity can impair the drug response to MM and allow for recurrence and/or disease progression.

12.
Curr Med Imaging ; 2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35770409

RESUMEN

BACKGROUND AND PURPOSE: During epidemics with an increased prevalence of pulmonary infections, extending stroke CTA examinations of acute stroke workup to the whole chest may allow for the identification of pulmonary findings that would have been missed on standard CTA examinations. MATERIALS AND METHODS: Our analysis comprised 216 patients with suspicion of stroke who received extended full-chest cerebrovascular CTA examinations from January 27th 2020 - date of the first confirmed Covid-19 case in Germany - until April 30th 2020. RESULTS: Consolidations and ground-glass opacifications were found in 73 of all 216 patients (34%). Opacifications were found in the upper chest in 51/216 patients (23%). There were lower-chest opacifications in 22 of 165 patients (13%) with unsuspicious upper-chest scans. In these 22 patients, there were consolidations in 10 cases (45%), ground-glass opacifications in 10 cases (45%), and both in 2 cases (10%). CONCLUSIONS: Our study showed that extending the scan volume of an emergency stroke CTA to the whole chest reveals a considerable number of opacifications that would have been missed on a standard CTA. Even though these findings were rarely indicative of COVID-19, a large number of opacifications warranted further investigation.

13.
PLoS One ; 17(10): e0275756, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36256639

RESUMEN

Knowledge of platelet function in pigs and the effectiveness of antiplatelet therapy is important to ensure proper transferability from animal studies to humans. Our aim was to (1) characterize baseline platelet function of Aachen minipigs using the bedside Multiplate analyzer, (2) compare baseline platelet function with Göttingen minipigs, and (3) characterize platelet inhibition within the first 5 minutes after intravenous administration of acetylsalicylic acid (ASA). We characterized the baseline platelet function and hematological parameters in 9 Aachen minipigs. Historical data of 8 unmedicated Göttingen minipigs were used for comparison of baseline values. Platelet inhibition in Aachen minipigs was tested 1-5 minutes after intravenous administration of 500 mg ASA. Multiplate examinations included the following tests: ASPI test (to assess the effect of ASA), adenosine-diphosphate-test (ADP test) and thrombin receptor activating peptide test (TRAP test). Median values and interquartile range (IQR) of the Multiplate baseline tests in Aachen minipigs were as follows: ASPI: 39 U (IQR = 21-71), ADP: 70 U (IQR = 48-73), and TRAP: 8 U (IQR = 6-9), whereas the values in Göttingen minipigs were as follows: ASPI: 70.5 U (IQR = 60-78), ADP: 51 U (IQR = 45-66), and TRAP: 6.5 U (IQR = 4-8). ASPI values of Göttingen minipigs were significantly higher than those of Aachen minipigs (p = 0.046). Intravenous administration of ASA in Aachen minipigs resulted in significant platelet inhibition after 1 minute, which remained stable over a period of 5 minutes (p≤0.038). Aachen minipigs appeared to have a high variance in arachidonic acid-mediated platelet aggregation. In Aachen minipigs, intravenous ASA administration resulted in immediate platelet inhibition.


Asunto(s)
Aspirina , Inhibidores de Agregación Plaquetaria , Humanos , Porcinos , Animales , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Porcinos Enanos , Ácido Araquidónico/farmacología , Difosfatos/farmacología , Pruebas de Función Plaquetaria/métodos , Agregación Plaquetaria , Plaquetas , Adenosina Difosfato/farmacología , Receptores de Trombina , Adenosina/farmacología
14.
PLoS One ; 16(5): e0251889, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34010332

RESUMEN

BACKGROUND AND PURPOSE: During a period of 6 months, we provided our entire neuroradiological staff including physicians, radiographers, and researchers with systematic feedback via email on the further clinical course of stroke patients who underwent mechanical thrombectomy. We analyzed the effects of this feedback on work satisfaction, work meaningfulness and valuation of the therapy among our staff. METHODS: Our staff completed two self-reported questionnaires before and after the period of six months with systematic feedback. RESULTS: Employees with higher work meaningfulness and higher work satisfaction valuated endovascular stroke therapy as more useful (p<0.001). A good clinical outcome was regarded more motivating than a good interventional outcome (p<0.001). Receiving systematic feedback did not increase work satisfaction (p = 0.318) or work meaningfulness (p = 0.178). Radiographers valuated the usefulness of interventional therapy the worst of all employees (p≤ 0.017). After the feedback period, 75% of radiographers estimated stroke as a more severe disease than before. Also, their desire for feedback decreased significantly (p = 0.007). Primarily patient cases with unfavorable outcomes were remembered by the staff. CONCLUSIONS: Systematic email feedback does not per se enhance work satisfaction or work meaningfulness among employees. However, receiving feedback is educative for the staff. Evaluating work satisfaction and the perception of treatment may help to identify unexpected issues and may therefore help to find specific measures that increase work satisfaction and motivation.


Asunto(s)
Retroalimentación Formativa , Satisfacción en el Trabajo , Médicos/psicología , Radiólogos/psicología , Investigadores/psicología , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Motivación , Autoinforme , Resultado del Tratamiento
15.
Science ; 373(6554)2021 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-34326208

RESUMEN

Emerging studies indicate that the immune system can regulate systemic metabolism. Here, we show that thymic stromal lymphopoietin (TSLP) stimulates T cells to induce selective white adipose loss, which protects against obesity, improves glucose metabolism, and mitigates nonalcoholic steatohepatitis. Unexpectedly, adipose loss was not caused by alterations in food intake, absorption, or energy expenditure. Rather, it was induced by the excessive loss of lipids through the skin as sebum. TSLP and T cells regulated sebum release and sebum-associated antimicrobial peptide expression in the steady state. In human skin, TSLP expression correlated directly with sebum-associated gene expression. Thus, we establish a paradigm in which adipose loss can be achieved by means of sebum hypersecretion and uncover a role for adaptive immunity in skin barrier function through sebum secretion.


Asunto(s)
Tejido Adiposo Blanco/anatomía & histología , Citocinas/metabolismo , Sebo/metabolismo , Piel/metabolismo , Inmunidad Adaptativa , Animales , Citocinas/genética , Dieta , Glucosa/metabolismo , Homeostasis , Humanos , Inmunoglobulinas/metabolismo , Metabolismo de los Lípidos , Ratones , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/prevención & control , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Receptores de Citocinas/metabolismo , Glándulas Sebáceas/metabolismo , Transducción de Señal , Piel/inmunología , Linfocitos T/fisiología , Pérdida de Peso , Linfopoyetina del Estroma Tímico
16.
Kidney360 ; 2(11): 1770-1780, 2021 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-35372991

RESUMEN

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.


Asunto(s)
COVID-19 , Glomerulonefritis por IGA , Apolipoproteína L1 , Vacunas contra la COVID-19/efectos adversos , Glomerulonefritis por IGA/epidemiología , Humanos , Pandemias , SARS-CoV-2 , Vacunación/efectos adversos
17.
J Neurosurg ; 134(2): 565-575, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-31923894

RESUMEN

OBJECTIVE: Aneurysm wall enhancement (AWE) on 3D vessel wall MRI (VWMRI) has been suggested as an imaging biomarker for intracranial aneurysms (IAs) at higher risk of rupture. While computational fluid dynamics (CFD) studies have been used to investigate the association between hemodynamic forces and rupture status of IAs, the role of hemodynamic forces in unruptured IAs with AWE is poorly understood. The authors investigated the role and implications of abnormal hemodynamics related to aneurysm pathophysiology in patients with AWE in unruptured IAs. METHODS: Twenty-five patients who had undergone digital subtraction angiography (DSA) and VWMRI studies from September 2016 to September 2017 were included, resulting in 22 patients with 25 IAs, 9 with and 16 without AWE. High-resolution CFD models of hemodynamics were created from DSA images. Univariate and multivariate analyses were performed to investigate the association between AWE and conventional morphological and hemodynamic parameters. Normalized MRI signal intensity was quantified and quantitatively associated with wall shear stresses (WSSs) for the entire aneurysm sac, and in regions of low, intermediate, and high WSS. RESULTS: The AWE group had lower WSS (p < 0.01) and sac-averaged velocity (p < 0.01) and larger aneurysm size (p < 0.001) and size ratio (p = 0.0251) than the non-AWE group. From multivariate analysis of both hemodynamic and morphological factors, only low WSS was found to be independently associated with AWE. Sac-averaged normalized MRI signal intensity correlated with WSS and was significantly different in regions of low WSS compared to regions of intermediate (p = 0.018) and high (p < 0.001) WSS. CONCLUSIONS: The presence of AWE was associated with morphological and hemodynamic factors related to rupture risk. Low WSS was found to be an independent predictor of AWE. Our findings support the hypothesis that low WSS in IAs with AWE may indicate a growth and remodeling process that may predispose such aneurysms to rupture; however, a causality between the two cannot be established.

18.
Clin Pract ; 8(1): 1047, 2018 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-29619161

RESUMEN

Black blood magnetic resonance imaging (MRI)is a promising imaging tool in predicting aneurysm rupture. Could it be also valuable in evaluating the treatment effect of endovascular and conservative treated aneurysms? Two patients were treated with stent and coil and one with Aspirine (ASS). Correlation of treatment response and contrast enhancement of the aneurysm wall is examined. In the first case stenting failed to treat the aneurysm and contrast enhancement in the wall did never subside during follow up black blood MRI. In the second case the aneurysm responded well to stenting and decreased in size, which was correlating significantly with attenuation of contrast enhancement in black blood MRI. In the third case the aneurysm responded to ASS treatment by decreasing in size as shown in follow up MR-angiography and the contrast enhancement in its wall decreased after 8 months of therapy. Black blood MRI seems to be a promising tool not only in predicting aneurysms at risk of rupture, but also in observing treatment responses after endovascular procedures or even Aspirine administration. When contrast enhancement decreases, aneurysm treatment seems to be successful as can be shown in decreasing size in the follow up angiography.

19.
Clin Pract ; 8(3): 1089, 2018 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-30101005

RESUMEN

The increasing number of incidental intracranial aneurysms creates a dilemma of which aneurysms to treat and which to observe. Clinical scoring systems consider risk factors for aneurysm rupture however objective parameters for assessment of aneurysms stability are needed. We retrospectively analysed contrast enhancing behaviour of un-ruptured aneurysms in the black blood magnetic resonance imaging (MRI) in N=71 patients with 90 aneurysms and assessed correlation between aneurysm wall contrast enhancement (AWCE) and aneurysm anatomy and clinical scoring systems. AWCE is associated with aneurysm height and height to width ratio in ICA aneurysms. AWCE is correlated to larger aneurysms in every anatomical location evaluated. However the mean size of the contrast enhancing aneurysms is significantly different between anatomical localizations indicating separate analyses for every artery. Clinical scoring systems like PHASES and UIATS correlate positively with AWCE in black blood MRI. MRI aneurysm wall contrast enhancement is a positive predictor for aneurysm instability and should be routinely assessed in follow up of incidental aneurysms. Aneurysms smaller than 7 mm with AWCE should be followed closely with focus on growth, as they may be prone to growth and rupture.

20.
Chin Neurosurg J ; 4: 10, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-32922871

RESUMEN

BACKGROUND: Inflammatory responses are implicated as crucial patho-mechanisms of vascular brain malformations. Inflammation is suggested to be a key contributor to aneurysm rupture; however it is unclear whether inflammation contributes similarly to bleeding of cerebral cavernous malformations (CCMs). Black blood MRI is a sequence which identifies inflammation in blood vessel walls and in the present study is used to detect inflammatory response in CCMs. METHODS: Fifteen patients with 17 CCMs treated in our department in 2017 were retrospectively analysed. All patients received black blood MRIs and the results were analysed in correlation with, size and bleeding of CCMs. RESULTS: Size and bleeding status of CCMs did not correlate with contrast enhancement in the CCM wall. One of 3 patients with bleeding displayed contrast enhancement in black blood MRI, whereas the others had non enhancing lesions. Because of the small number of cases a statistical analysis was not performed. CONCLUSION: In this limited cohort, inflammatory reactions in CCMs could not be detected by black blood MRI suggesting that the level of inflammation is minimal in these lesions and those different patho-mechanisms play a more important role in the rupture of CCMs.

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