RESUMEN
The risk of recurrence in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy depends on the pathological tumor stage. In particular, patients with lymph node metastasis (pN+), locally advanced (≥pT3), or residual muscle invasive tumor despite neoadjuvant chemotherapy are at high risk. Currently, the importance of adjuvant therapy with immune checkpoint inhibitors is increasing in the context of perioperative systemic therapeutic concepts. The indication for the PD1 inhibitor nivolumab currently approved in the European Union requires testing of PD-L1 (programmed cell death ligand 1) protein expression by immunochemistry in tumor tissue. Focusing on MIBC patients at high risk of recurrence, new questions arise regarding the implementation and interpretation of PD-L1 testing. An interdisciplinary group of experts from Germany has discussed relevant issues from a clinicopathological point of view and developed practical recommendations to facilitate the implementation of validated and quality-assured PD-L1 testing for the approved indications in daily clinical practice.
RESUMEN
As a result of the high approval dynamics and the growing number of immuno-oncological therapy concepts, the complexity of therapy decisions and control in the area of carcinomas of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand 1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken a position on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.
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Carcinoma , Neoplasias Gástricas , Humanos , Antígeno B7-H1/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores , Esófago/metabolismoRESUMEN
As a result of the high approval dynamics and the growing number of immuno-oncological concepts, the complexity of treatment decisions and control in the area of cancers of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD-1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand 1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken a position on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.
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Antígeno B7-H1 , Carcinoma , Humanos , Antígeno B7-H1/metabolismo , Biomarcadores , Esófago , Unión Esofagogástrica/patología , Carcinoma/patología , Biomarcadores de Tumor/metabolismoRESUMEN
A case report is presented of fulminant hydroxychloroquine-induced cardiomyopathy in a 57 year-old female patient with a long history of systemic lupus erythematosus. Diagnosis was established based on clinical findings, imaging (echocardiography and cardiac magnetic resonance imaging) as well as endomyocardial biopsy. Despite immediate discontinuation of the medication, the patient died from heart failure within a few days. Since the rare adverse effect described here might be reversible, early diagnosis and discontinuation of hydroxychloroquine are crucial for the prognosis of these patients.
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Cardiomiopatías/inducido químicamente , Insuficiencia Cardíaca/mortalidad , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedades Musculares/inducido químicamente , Biopsia , Cardiomiopatías/mortalidad , Ecocardiografía , Resultado Fatal , Femenino , Corazón/efectos de los fármacos , Insuficiencia Cardíaca/inducido químicamente , Humanos , Hidroxicloroquina/uso terapéutico , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
PURPOSE: We propose CD3-antibody-mediated contrast-enhanced ultrasonography using human T-lymphocytes for image-based diagnosis of acute allograft rejection (AR) established in a rat renal transplantation model. MATERIALS AND METHODS: 15 minutes after tail vein injection of 30â×â10(6) human T-lymphocytes, contrast media/microbubbles conjugated with an anti-human CD3 antibody was applied to uni-nephrectomized 10-week-old allogeneically transplanted male rats (Lewis-Brown Norway (LBN) to Lewis, aTX) and ultrasound was performed to investigate the transplanted kidney as well as the native kidney. In vivo results were confirmed via immunohistochemical stainings of CD3 after post mortem dissection. Syngeneically transplanted rats (LBN to LBN, sTX), rats with ischemia/reperfusion injury (IRI, 45âmin. warm ischemia), and rats subjected to acute cyclosporin A toxicity (CSA) (cyclosporine 50âmg/kg BW for 2 days i.âp.) served as controls. RESULTS: Accumulation of human T-lymphocytes was clearly detected by antibody-mediated sonography und was significantly increased in allografts undergoing AR (5.41â±â1.32 A.âU.) when compared to native control kidneys (0.70â±â0.08 A.âU.). CD3 signal intensity was low in native kidneys, sTX (0.99â±â0.30 A.âU.), CSA (0.10â±â0.02 A.âU.) and kidneys with IRI (0.46â±â0.29 A.âU.). Quantification of the ultrasound signal correlated significantly with the T-cell numbers obtained by immunohistochemical analysis (R2â=â0.57). CONCLUSION: Contrast-enhanced sonography using CD3-antibodies is an option for quick and highly specific assessment of AR in a rat model of renal transplantation.
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Anticuerpos/inmunología , Complejo CD3/inmunología , Modelos Animales de Enfermedad , Rechazo de Injerto/diagnóstico por imagen , Trasplante de Riñón , Microburbujas , Imagen Molecular , Linfocitos T , Ultrasonografía , Enfermedad Aguda , Animales , Rechazo de Injerto/patología , Riñón/diagnóstico por imagen , Riñón/patología , Masculino , Ratas , Ratas Endogámicas Lew , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody-mediated contrast-enhanced ultrasound by using microbubbles targeted to CD3(+) , CD4(+) , or CD8(+) T cells in different models of renal disease. In an established rat renal transplantation model, CD3-mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast-enhanced sonography. Notably, acute tubular necrosis occurring after ischemia-reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM-1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody-mediated contrast-enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation.
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Complejo CD3/inmunología , Rechazo de Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Imagen Molecular/métodos , Daño por Reperfusión/complicaciones , Linfocitos T/inmunología , Ultrasonografía/métodos , Enfermedad Aguda , Animales , Inhibidores de la Calcineurina/toxicidad , Medios de Contraste/metabolismo , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/etiología , Isoanticuerpos/toxicidad , Necrosis Tubular Aguda/diagnóstico , Necrosis Tubular Aguda/diagnóstico por imagen , Necrosis Tubular Aguda/etiología , Masculino , Microburbujas , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Daño por Reperfusión/cirugía , Trasplante HomólogoRESUMEN
Early detection of prognostically significant coronary artery disease (CAD) using ischemic tests, including noninvasive cardiac imaging, are fundamental approaches of optimized patient treatment guidelines to lower morbidity and mortality of these patients. Current international guidelines and the national standard of care guidelines from 2006 and 2011 as well as the third universal definition of myocardial infarction stress the increasing role of echocardiography as a favorable noninvasive imaging test. Echocardiography at rest, ergometric and pharmacologic stress echocardiography are established and readily available diagnostic tools with the potential to evaluate global and regional left ventricular function at rest and during exercise combined with information regarding regional perfusion. Especially new data on perfusion analysis allow further extension of the indications spectrum of reperfusion analysis and sensitivity increases in chest pain unit settings. The noninvasive detection of significant and prognostic stenosis burden in CAD without radiation is possible with high sensitivity and good specificity and encompasses functional cardiovascular parameters as well as extension of the ischemic area.The likelihood of future cardiac events can be assessed with high negative predictive accuracy, giving a high safety aspect in the treatment options of patients. The diagnostic potential of stress echocardiography is best in patients with intermediate and higher pretest probabilities. In patients under concurrent antiischemic medication identification of high risk patients seems feasible. Stress echocardiography has an excellent specificity and prognostic value for either indications for revascularization or survival prediction as well as survival benefits after revascularization in test positive patients.The detection of pathologic findings is not impaired by gender differences. New technical approaches include 2-D and 3-D speckle analysis of the myocardial wall and contrast-enhanced improvements in myocardial border delineation and perfusion. A new European multicenter study published in 2013 could demonstrate comparable to improved sensitivities in intermediate to severe coronary stenosis from 50% to 70% and in highly obstructive proximal stenoses compared to a reference electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT).
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Angina Estable/diagnóstico , Angina Estable/prevención & control , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Ecocardiografía/métodos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/terapia , Angina Estable/etiología , Enfermedad Crónica , Enfermedad de la Arteria Coronaria/complicaciones , Técnicas de Diagnóstico Cardiovascular , Humanos , Isquemia Miocárdica/complicacionesRESUMEN
A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1-6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4-6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4-6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.
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Adaptación Fisiológica/fisiología , Corazón/fisiología , Condicionamiento Físico Animal/fisiología , Superóxido Dismutasa/genética , Remodelación Ventricular/fisiología , Adaptación Fisiológica/genética , Animales , Antioxidantes/metabolismo , Apoptosis/genética , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatología , Regulación hacia Abajo , Heterocigoto , Homeostasis , Masculino , Ratones , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Oxidación-Reducción , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Peroxirredoxinas/genética , Isoformas de Proteínas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/deficiencia , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Remodelación Ventricular/genéticaRESUMEN
PROBLEMS/OBJECTIVES: Epstein-Barr virus (EBV) is commonly associated with nasopharyngeal carcinoma and Burkitt's lymphoma, but association with hypopharyngeal and laryngeal tumours is rare. To the best of our knowledge, this is the first case report of an EBV-associated diffuse large B-cell lymphoma (DLBCL) of the hypopharynx. METHODOLOGY: A 63-year-old male patient suffering from chronic lymphocytic leukemia presented with swallowing disorders and a sore throat. Panendoscopy with laser surgical resection of tissue specimens was performed. RESULTS: Immunohistochemical and molecular genetic diagnostics, including EBV-encoded small RNA in situ hybridization, confirmed the diagnosis of an EBV-associated DLBCL of the hypopharynx. Ten weeks after the diagnosis, the patient died of disease related to multiple complications. CONCLUSIONS: We hypothesize that the EBV infection was triggered by long-term immunosuppressive therapy that led secondarily to the development of a DLBCL. Otorhinolaryngologists should keep in mind that lymphomas might develop in the entire pharynx.
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Infecciones por Virus de Epstein-Barr/complicaciones , Neoplasias Hipofaríngeas/virología , Linfoma de Células B Grandes Difuso/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Resultado Fatal , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagen , Neoplasias Hipofaríngeas/epidemiología , Huésped Inmunocomprometido , Inmunohistoquímica , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/epidemiología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Persona de Mediana Edad , Seno Piriforme/virología , Tomografía Computarizada por Rayos XRESUMEN
The present study investigated cardiac function in hearts of mice with total deficiency of the beta1-, beta2- and beta3-adrenoceptors (TKO) in comparison to wildtype mice (WT). We investigated cardiac morphology and echocardiographic function, measured protein expression of Ca2+-regulatory proteins, SERCA 2a activity, myofibrillar function, and performed running wheel tests. Heart weight and heart-to-body weight ratio were significantly smaller in TKO as compared to WT. This was accompanied by a decrease in the size of the cardiomyocytes in TKO. Heart rate and ejection fraction were significantly diminished in TKO as compared to WT. Protein expressions of SERCA 2a, ryanodine receptor and Na+/Ca2)-exchanger were similar in TKO and WT mice, but phospholamban protein expression was increased. PKA-dependent phosphorylation of phospholamban at serine 16 was absent and CaMKII-dependent phosphorylation at threonine 17 was decreased in TKO. All alterations were paralleled by a decrease in SERCA 2a-activity. A similar maximal calcium-dependent tension but an increased myofibrillar calcium-sensitivity was measured in TKO as compared to WT. We did not observe relevant functional impairments of TKO in running wheel tests. In the absence of beta-agonistic stimulation, SERCA 2a activity is mainly regulated by alterations of phospholamban expression and phosphorylation. The decreased SERCA 2a activity following beta-adrenoceptor deficiency may be partly compensated by an increased myofibrillar calcium-sensitivity.
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Cardiomegalia/fisiopatología , Contracción Miocárdica/fisiología , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 3/genética , Animales , Cardiomegalia/diagnóstico por imagen , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Ecocardiografía , Femenino , Ratones , Ratones Noqueados , Miofibrillas/fisiología , Fosforilación/fisiología , Condicionamiento Físico Animal/fisiología , Receptores Adrenérgicos beta 1/deficiencia , Receptores Adrenérgicos beta 2/deficiencia , Receptores Adrenérgicos beta 3/deficiencia , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Intercambiador de Sodio-Calcio/metabolismoRESUMEN
Little is known about sex-dependent physiological and pathophysiological differences in cardiac endothelial nitric oxide synthase (eNOS) expression and activation. Therefore, we investigated cardiac morphology and eNOS protein expression, including its translocation-dependent activation and phosphorylation, in cardiac tissue of male and female wild-type mice and transgenic heart-failure mice having a cardiac-specific, 5-fold overexpression of the Galphaq protein. In addition, we measured calcineurin protein expression. Heart-to-body weight ratio was increased in Galphaq mice. Female wild-type mice showed higher eNOS protein expression and activation (translocation and phosphorylation) than did wild-type males. In cardiac tissue of Galphaq mice, these sex-dependent differences remained or were enhanced. Protein expression of the catalytic subunit calcineurin A, which has been shown to dephosphorylate eNOS, was higher in wild-type males than in wild-type females. These differences were increased in the Galphaq mice model. We conclude that sex differences exist in cardiac eNOS protein expression and phosphorylation. Increased activation of the Galphaq protein appears to alter eNOS protein expression and phosphorylation only in males.
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Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Caracteres Sexuales , Secuencia de Aminoácidos , Animales , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/biosíntesis , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Óxido Nítrico Sintasa de Tipo III/genética , Fosforilación/genética , Biosíntesis de Proteínas/genética , Transporte de Proteínas/genéticaRESUMEN
This report presents the first case of complete resolution of ascites after transcoronary ablation of septal hypertrophy (TASH) in a cirrhotic patient with concomitant hypertrophic cardiomyopathy (HOCM). A 52-years-old woman with decompensated alcoholic liver cirrhosis was referred to our department for placement of a transjugular intrahepatic portosystemic stent shunt (TIPS) to treat her refractory ascites. The initial treatment with furosemide and spironolactone had to be discontinued because of severe hyponatriemia and an increase of creatinine levels. During further evaluation, HOCM was diagnosed by echocardiography and cardiac catheterization. We performed TASH in order to relieve the dynamic obstruction of the ventricular outflow tract, and the ascites completely resolved without further interventions.
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Ascitis/cirugía , Cardiomiopatía Hipertrófica/cirugía , Ablación por Catéter/efectos adversos , Tabiques Cardíacos/cirugía , Cirrosis Hepática/cirugía , Derivación Portosistémica Quirúrgica , Ascitis/tratamiento farmacológico , Ascitis/etiología , Cardiomiopatía Hipertrófica/complicaciones , Femenino , Humanos , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Studies have shown that biomaterials have the capacity to adsorb heavy metals and metal oxo-cations from aqueous solution. In addition, previous studies have shown that biomaterials have the ability to bind uranyl cations from solution with capacities that are comparable to or greater than some commercially available synthetic ion-exchange resins. By using chemical modification, inductively coupled plasma optical emission spectroscopy (ICP-OES), and X-ray absorption spectroscopy (XAS), we have found that the primary functional group on alfalfa biomass responsible for the binding of uranyl cations from aqueous solution is the carboxyl functionality. Batch pH dependency experiments show a direct relationship between the increase in binding and the increase in pH (up to pH 4.5). XAS experiments showed that the major ligand involved in the binding of uranyl cations from aqueous solution was either a nitrogen or oxygen ligand with coordination numbers ranging from 6 to 10 +/- 1.
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Medicago sativa/química , Uranio/metabolismo , Adsorción , Biomasa , Carbono/química , Cationes/química , Concentración de Iones de Hidrógeno , Medicago sativa/metabolismo , Nitrógeno/química , Oxígeno/química , Soluciones , Espectrofotometría Atómica , Análisis Espectral , Uranio/químicaRESUMEN
Metal stents are a valuable treatment modality for patients with biliary obstruction. However, we present here two patients whose cases may serve as a warning about an unusual complication associated with these stents. We encountered this complication after endoscopic retrograde cholangiography for obstructed metal biliary stents. The first patient, an 87-year-old man with a benign biliary stricture, failed to regain consciousness after clearing of his stent using a Dormia basket and balloon catheter. Cerebral air embolism was diagnosed on cerebral computed tomography, and transesophageal echocardiography revealed a patent foramen ovale as a precipitating factor for paradoxical air embolism. He survived and was discharged with a residual hemiparesis. In the second patient, a 54-year-old man who had a history of a Billroth II operation and chronic pancreatitis and who had a portal cavernoma with biliary obstruction due to collateral veins, electromechanical dissociation complicated the balloon-catheter stent revision. Echocardiography performed during cardiopulmonary resuscitation showed major air embolism to the right heart. The patient died. These cases demonstrate that air may gain access to the venous system during therapeutic endoscopic procedures of this type. It is likely that the large diameter of metal stents and the potential for these stents to lacerate venous structures facilitate the entry of air into the venous circulation, an event which may have life-threatening consequences.
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Colestasis Extrahepática/cirugía , Embolia Aérea/etiología , Embolia Intracraneal/etiología , Implantación de Prótesis/instrumentación , Stents/efectos adversos , Anciano de 80 o más Años , Embolia Aérea/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Embolia Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Falla de Prótesis , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
Rupture of a sinus of Valsalva aneurysm (SVA) is a rare, but life-threatening, event and requires immediate recognition and intervention. We present two previously healthy and physically active patients who were 12 and 33 years of age when rupture of a right coronary SVA into the right ventricle occurred. A subarterial ventricular septal defect (VSD) was detectable in both patients. Cardiac surgery involved VSD closure as well as reconstruction of the aortic valve. Considering complications of subarterial VSD, such as aortic cusp prolapse, aortic insufficiency or SVA, we suggest close follow-up and surgical closure of the VSD in case of any aortic valve deformity.
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Rotura de la Aorta/epidemiología , Rotura de la Aorta/cirugía , Procedimientos Quirúrgicos Cardíacos , Defectos del Tabique Interventricular/epidemiología , Defectos del Tabique Interventricular/cirugía , Seno Aórtico , Adulto , Niño , Comorbilidad , Defectos del Tabique Interventricular/diagnóstico por imagen , Humanos , Masculino , UltrasonografíaRESUMEN
PURPOSE: Patients (pts.) with atrial fibrillation (AF) and atrial thrombi are known to have an increased risk for cerebral embolism. However, little is known about the clinical course of atrial thrombi and the incidence of cerebral embolism in those patients during anticoagulation therapy. The high sensitivity of MR imaging (MRI) including diffusion-weighted imaging (DWI) suggests that this technique could provide an improved estimate of cerebral embolism associated with the presence of left atrial thrombi. The aims of this prospective study were to evaluate 1) the prevalence of clinically silent and apparent cerebral embolism in pts. with newly diagnosed AF and atrial thrombi using MRI/DWI, 2) the long-term fate of atrial thrombi under continues anticoagulation therapy and 3) the incidence of cerebral embolism during a follow-up period of 12 months with continuous anticoagulation therapy. MATERIALS AND METHODS: The study group consisted of 32 pts. with 1) newly diagnosed AF and evidence of left atrial (LA) thrombi detected by TEE and 2) a new start of anticoagulation therapy [International Normalized Ratio (INR) 2.0 - 3.0]. 19 pts. with 1) newly diagnosed AF and no evidence of atrial thrombi and 2) an equivalent anticoagulation regimen served as the control group. In both groups a) MRI/DWI studies of the brain (weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52), b) transesophageal echocardiographic studies (TEE) for assessment of LA-Thrombi (weeks 0 and 52) and c) clinical neurological assessments (weeks 0, 20 and 52) were performed. RESULTS: In the study group (AF and LA-Thrombi) 11 out of 32 pts. (34 %) displayed signs of acute (n = 8) or chronic (n = 3) cerebral embolism in the initial MRI studies. In 4 out of 32 pts. (13 %), MRI/DWI depicted new or additional cerebral emboli (n = 12) during the follow-up period despite continuous anticoagulation therapy. 2 (n = 2/4; 50 %) of these patients had clinically apparent neurological deficits. In the control group 1 out of 19 pts. (5 %) showed evidence of chronic cerebral embolism as assessed by MRI/DWI at the beginning of the study (week 0). No embolic cerebral lesions were detected during the 12-month follow-up. Within 12 months only 63 % (n = 20/32) of LA thrombi in the study group resolved completely under anticoagulation. CONCLUSION: 1. The incidence of clinically inapparent cerebral emboli in pts. with newly diagnosed AF and atrial thrombi is much higher than the incidence of clinically apparent emboli and has been underestimated in the past. 2. New cerebral embolism may occur even with continued effective anticoagulation therapy in 13 % of pts. 3. Only 63 % of atrial thrombi resolve completely within 12 months under anticoagulation therapy.
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Anticoagulantes/administración & dosificación , Antifibrinolíticos/administración & dosificación , Fibrilación Atrial/complicaciones , Atrios Cardíacos , Cardiopatías/complicaciones , Cardiopatías/tratamiento farmacológico , Heparina/administración & dosificación , Embolia Intracraneal/diagnóstico , Imagen por Resonancia Magnética/métodos , Fenprocumón/administración & dosificación , Trombosis/complicaciones , Trombosis/tratamiento farmacológico , Anciano , Infarto Cerebral/diagnóstico , Imagen de Difusión por Resonancia Magnética , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Embolia Intracraneal/epidemiología , Embolia Intracraneal/etiología , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Estudios Prospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
This study aimed to evaluate the influence of a new navigator technique (3D MAG) on navigator efficiency, total acquisition time, image quality and diagnostic accuracy. Fifty-six patients with suspected coronary artery disease underwent free breathing navigator gated coronary MRA (Intera, Philips Medical Systems, 1.5 T, spatial resolution 0.9x0.9x3 mm3) with and without 3D MAG. Evaluation of both sequences included: 1) navigator scan efficiency, 2) total acquisition time, 3) assessment of image quality and 4) detection of stenoses >50%. Average navigator efficiencies of the LCA and RCA were 43+/-12% and 42+/-12% with and 36+/-16% and 35+/-16% without 3D MAG (P<0.01). Scan time was reduced from 12 min 7 s without to 8 min 55 s with 3D MAG for the LCA and from 12 min 19 s to 9 min 7 s with 3D MAG for the RCA (P<0.01). The average scores of image quality of the coronary MRAs with and without 3D MAG were 3.5+/-0.79 and 3.46+/-0.84 (P>0.05). There was no significant difference in the sensitivity and specificity in the detection of coronary artery stenoses between coronary MRAs with and without 3D MAG (P>0.05). 3D MAG provides accelerated acquisition of navigator gated coronary MRA by about 19% while maintaining image quality and diagnostic accuracy.
Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Imagenología Tridimensional , Angiografía por Resonancia Magnética/métodos , Anciano , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
PURPOSE: A major problem of free breathing coronary MR angiography (MRA) with respiratory navigator gating is low navigator efficiency and prolonged scan time due to irregular breathing patterns. 3D motion adapted gating (MAG) is a new adaptive navigator technique, which adapts in real time to changes of the end-expiratory position of diaphragm. This study evaluates the influence of 3D MAG on coronary MRA. METHODS AND MATERIALS: In 3D MAG, two additional gating windows are grouped around the conventional window. Additionally, each gating window is divided into three bands assigned to different portions of the k-space. The scan is terminated when three consecutive bands are filled and one complete image data set is collected. Free breathing navigator-gated coronary MRA was performed on 48 patients with suspected coronary artery disease. In random order, each patient underwent an ECG-gated, a 3D segmented k-space gradient echo sequence using 3D MAG and a conventional navigator technique. The coronary MRA was evaluated and compared using the following parameters: 1. navigator efficiency and scan time; 2. visualized coronary artery length; 3. qualitative assessment of image quality; and 4. detection of stenoses > 50 % in comparison with catheter angiography. RESULTS: Coronary MRA with 3D MAG had a significant increase in the average navigator efficiency (46 % +/- 12 % vs. 38 % +/- 12 %, p < 0.05), resulting in a significantly shorter scan time (mean: 18 % +/- 4 %, p < 0.05) for coronary MRA with 3D MAG compared to conventional navigator technique. Scans with and without 3D MAG had no significant differences in the continuously visualized vessel lengths, in the assessed image quality and in the sensitivity and specificity (83 % and 89 % vs. 83 % and 88 %, p > 0.05) of detecting coronary artery stenoses > 50 %. CONCLUSION: The 3D MAG technique improves the navigator efficiency and significantly (p < 0.05) shortens the scan time of navigator gated coronary MRA while maintaining image quality and diagnostic accuracy in the detection of coronary artery stenoses.
Asunto(s)
Enfermedad Coronaria/diagnóstico , Angiografía por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estenosis Coronaria/diagnóstico , Interpretación Estadística de Datos , Electrocardiografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana EdadRESUMEN
Metal pollution in the aqueous environment has become an important issue in the past few decades leading to extensive research in the area of pollution remediation. Most of the recent research in this area has been in bioremediation including phytofiltration and phytoextraction. Although there has been a lot of research done in the field of metal interactions with plants, the actual mechanism(s) and ligands involved are not well understood. Through a series of batch experiments, including pH profiles, time dependency studies, and capacity experiments, we have investigated the binding of Gd(III) and Nd(III) to alfalfa biomass. Batch pH studies showed that the optimum binding was at pH 5.0 for both elements. The time dependency experiments showed that the binding occurs within the first 5min of contact and remains constant for up to 60min. In addition, chemical modifications to the alfalfa biomass were performed to indirectly determine the ligands on the biomass responsible for metal binding. For Gd(III) binding, it was shown that the carboxyl groups on the biomass play the most important role in metal ion binding. However, for Nd(III), not only was it found that the carboxyl groups play an important role in the binding, but in addition, the amino groups on the biomass also play an important role in the binding of the metal ions. Further studies using X-ray absorption spectroscopy (XAS) showed that the Gd(III) and Nd(III) ions were bound to the alfalfa biomass through oxygen (or nitrogen ligands), which were coordinated to carbon atoms. The lanthanide complexes within the biomass included some coordinated water molecules.