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[Figure: see text].
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Factor-23 de Crecimiento de Fibroblastos/sangre , Hidroxicolecalciferoles/uso terapéutico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Péptidos/uso terapéutico , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Muerte Súbita Cardíaca/prevención & control , Progresión de la Enfermedad , Femenino , Humanos , Hidroxicolecalciferoles/administración & dosificación , Hidroxicolecalciferoles/efectos adversos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Hipocalcemia/inducido químicamente , Análisis de Intención de Tratar , Proteínas Klotho/sangre , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Péptidos/administración & dosificación , Péptidos/efectos adversos , Fosfatos/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Método Simple CiegoRESUMEN
BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding the risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes. METHODS: In this prospective, multicentre, population-based cohort study, GDF-15 was measured in 594 ESKD patients on haemodialysis (median age 66 years, 38% female), who were followed up for a median of 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE) and death was analysed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment. RESULTS: GDF-15 levels were in median 5475 ng/l (25th-75th percentile 3964-7533) and independently associated with major bleeding {subdistribution hazard ratio [SHR] 1.31 per double increase [95% confidence interval (CI) 1.00-1.71]}, MACE [SHR 1.47 (95% CI 1.11-1.94)] and all-cause mortality [SHR 1.58 (95% CI 1.28-1.95)] but not arterial thromboembolism [SHR 0.91 (95% CI 0.61-1.36)]. The addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding [C-statistics increased from 0.61 (95% CI 0.52-0.70) to 0.68 (95% CI 0.61-0.78)]. Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death. CONCLUSION: GDF-15 predicts the risk of major bleeding, cardiovascular events and death in ESKD patients on haemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.
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Fallo Renal Crónico , Tromboembolia , Humanos , Femenino , Anciano , Masculino , Estudios de Cohortes , Estudios Prospectivos , Factor 15 de Diferenciación de Crecimiento , Hemorragia/etiología , Hemorragia/epidemiología , Medición de Riesgo , Biomarcadores , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Calcimimetic therapy with etelcalcetide (ETEL) has been shown to attenuate the advancement of left ventricular (LV) hypertrophy in hemodialysis patients measured by cardiac magnetic resonance (CMR). The aim of the study was to evaluate whether this effect is accompanied by alterations in LV function and myocardial composition. METHODS: This was a post-hoc analysis of a randomized-controlled trial of ETEL versus Alfacalcidol (ALFA) in 62 hemodialysis patients. LV function was assessed using LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) on feature-tracking (FT) CMR. Myocardial tissue characteristics were analyzed using parametric T1 and T2 mapping. RESULTS: Of the total study cohort (n = 62), 48 subjects completed both CMR scans with sufficient quality for FT analysis. In the one-year follow-up, LV GLS deteriorated in the ALFA group, whereas the ETEL group remained stable (LV GLS change: + 2.6 ± 4.6 versus + 0.3 ± 3.8; p = 0.045 when adjusting for randomization factors and baseline LV GLS). We did not observe a difference in the change of LVEF between the two groups (p = 0.513). The impact of ETEL treatment on LV GLS over time remained significant after additional adjustment for the change in LV mass during the study period. ETEL treatment did not significantly affect other CMR parameters. There were no changes in myocardial composition between treatment groups (T1 time change: + 15 ± 42 versus + 10 ± 50; p = 0.411; T2 time change: - 0.13 ± 2.45 versus - 0.70 ± 2.43; p = 0.652). CONCLUSIONS: In patients undergoing hemodialysis, treatment with ETEL was protective against deterioration of LV longitudinal function, as evaluated through FT CMR, when compared to the control therapy of ALFA. This effect was not mediated by the change in LV mass. Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03182699 . Unique identifier: NCT03182699.
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Imagen por Resonancia Cinemagnética , Función Ventricular Izquierda , Humanos , Hipertrofia Ventricular Izquierda , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Diálisis Renal , Volumen Sistólico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation. METHODS: Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression. RESULTS: Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0-5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8-12.9) and 8.8 (5.7-13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10-1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14-1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06-3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14-0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01-1.38). CONCLUSION: In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.
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We introduce a technique for the directed transfer of molecules from an adjacent reservoir onto a sample surface inside the vacuum chamber of a ToF-SIMS instrument using gas cluster ion beam (GCIB) sputtering. An example application for in situ matrix-enhanced secondary ion mass spectrometry (ME SIMS) is provided. This protocol has attractive features since most modern SIMS instruments are equipped with a GCIB gun. No solvents are required that would delocalize analytes at the surface, and the transfer of matrix molecules can be interlaced with SIMS depth profiling and 3D imaging sputtering and analysis cycles, which is not possible with conventional ME SIMS strategies. The amount of molecular deposition can be finely tuned, which is important for such a surface sensitive technique as SIMS. To demonstrate the concept, we used 2,5-DHB as a matrix for the enhancement of three drug molecules embedded in a tissue homogenate. By automatic operation of sputter deposition and erosion (cleanup) cycles, depth profiling could be achieved with ME SIMS with good repeatability (<4% RSD). Furthermore, we explored several different matrix compounds, including α-CHCA and aqueous solutions of Brønsted acids (formic acid) and 3-nitrobenzonitrile, a volatile compound known to spontaneously produce ions. The latter two matrix compounds were applied at cryogenic measurement conditions, which extend the range of matrices applicable for ME SIMS. Enhancement ratios range from 2 to 13, depending on the analytes and matrix. The method works in principle, but enhancement ratios for the drug molecules are rather limited at this point. Further study and optimization is needed, and the technique introduced here provides a tool to perform systematic studies of matrix compounds and experimental conditions for their potential for signal enhancement in ME SIMS.
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The study of lipid molecular fossils by traditional biomarker analysis requires bulk sample crushing, followed by solvent extraction, and then the analysis of the extract by gas chromatography-mass spectrometry (GC-MS). This traditional analysis mixes all organic compounds in the sample regardless of their origins, with a loss of information on the spatial distribution of organic molecules within the sample. These shortcomings can be overcome using the chemical mapping of intact samples. Spectroscopic techniques such as UV fluorescence or Raman spectroscopy, laser ablation inductively coupled plasma mass spectrometry, and time-of-flight secondary ion mass spectrometry (ToF-SIMS) are among those elemental and molecular mapping techniques. This study employed femtosecond (fs) laser ablation combined with single-photon ionization, a method called fs-laser desorption postionization mass spectrometry (fs-LDPI-MS). A pulsed â¼75 fs, 800 nm laser was used to ablate the geological sample, which was then photoionized after a few microseconds by a pulsed 7.9 eV vacuum ultraviolet laser. An organic carbon-rich geological sample was used for this study to map hydrocarbon biomarkers in sediments that were previously studied by GC-MS. The petrography of this sample was examined by optical and fluorescence microscopy. It is demonstrated here that fs-LDPI-MS combined with petrography for multimodal imaging can expose buried compounds within the sample via in situ layer removal. When used in conjunction with traditional organic geochemical analysis, this method has the potential to determine the spatial distribution of organic biomarkers in geological material. Finally, fs-LDPI-MS imaging data are compared with ToF-SIMS imaging that is commonly used for such studies.
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Rayos Láser , Espectrometría de Masa de Ion Secundario , Biomarcadores , Diagnóstico por Imagen , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Sensitivity to molecular ions remains a limiting factor for high resolution imaging mass spectrometry of organic and biological materials. Here, we investigate a variant of matrix-enhanced secondary ion mass spectrometry in which the transfer of matrix molecules to the analyte sample is carried out in situ (in situ ME-SIMS). This approach is therefore compatible with both 2D and 3D imaging by SIMS. In this exploratory study, nanoscale matrix layers were sputter-transferred inside our time-of-flight (ToF)-SIMS to a series of thin films of biomolecules (proteins, sugars, lipids) adsorbed on silicon, and the resulting layers were analyzed and depth-profiled. For this purpose, matrix molecules were desorbed from a coated target (obtained by drop-casting or sublimation) using 10 keV Ar3000+ ion beam sputtering, followed by redeposition on a collector carrying the sample to be analyzed. After evaluating the quality of the transfer of six different matrices on bare Si collectors, α-cyano-4-hydroxycinnamic acid (CHCA) was selected for further experiments. The mass spectra and depth profiles obtained from the organic layer prior to and after the sputter-transfer of CHCA were compared, along with those obtained from regular ME-SIMS samples (dried droplets) and, finally, with MALDI data for the same matrix-analyte combinations. Signal amplification factors were calculated by dividing the integrated molecular intensities obtained with or without matrix transfer. While the amplification factors are between 0.5 and 2 for molecules already detected with high intensities in SIMS, such as cholesterol or human angiotensin, other compounds show very large integrated signal amplification, even above two orders of magnitude. This is the case for D-glucose and cardiolipin, for which the molecular ion intensity is low (or very low) under normal SIMS analysis conditions. For such low ionization probability compounds, the beneficial effect of the matrix is unquestionable. Test experiments on mouse brain tissue sections also indicate signal enhancement with the matrix, especially for high mass lipid ions.
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Lípidos , Espectrometría de Masa de Ion Secundario , Animales , Iones , Ratones , Silicio , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The ability to spatially resolve the chemical distribution of compounds on a surface is important in many applications ranging from biological to material science. To this extent, we have recently introduced a hybrid atomic force microscopy (AFM)-mass spectrometry (MS) system for direct thermal desorption and pyrolysis of material with nanoscale chemical resolution. However, spatially resolved direct surface heating using local thermal desorption becomes challenging on material surfaces with low melting points, because the material will undergo a melting phase transition due to heat dissipation prior to onset of thermal desorption. Therefore, we developed an approach using mechanical sampling and collection of surface materials on an AFM cantilever probe tip for real-time analysis directly from the AFM tip. This approach allows for material to be concentrated directly onto the probe for subsequent MS analysis. We evaluate the performance metrics of the technique and demonstrate localized MS sampling from a candelilla wax matrix containing UV stabilizers avobenzone and oxinoxate from areas down to 250 nm × 250 nm. Overall, this approach removes heat dissipation into the bulk material allowing for a faster desorption and concentration of the gas phase analyte from a single heating pulse enabling higher signal levels from a given amount of material in a single sampling spot.Graphical abstract.
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Metal-organic frameworks (MOFs) are a promising class of materials for many applications, due to their high chemical tunability and superb porosity. By growing MOFs as (thin-)films, additional properties and potential applications become available. Here, copper (II) 1,3,5-benzenetricarboxylate (Cu-BTC) metal-organic framework (MOF) thin-films are reported, which were synthesized by spin-coating, resulting in "nanowebs", that is, fiber-like structures. These surface-mounted MOFs (SURMOFs) were studied by using photoinduced force microscopy (PiFM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The optimal concentration of precursors (10â mm) was determined that resulted in chemically homogeneous, pure nanowebs. Furthermore, the morphology and (un)coordinated Cu sites in the web were tuned by varying the rotation speed of the spin-coating process. X-ray diffraction (XRD) analysis showed that rotation speeds ≥2000â rpm (with precursors in a water/ethanol solution) generate the catena-triaqua-µ-(1,3,5-benzenetricarboxylate)-copper(II), or Cu(BTC)(H2 O)3 coordination polymer. X-ray photoelectron spectroscopy (XPS) highlighted the strong decrease in number of (defective) Cu+ sites, as the nanowebs mainly consist of coordinated Cu2+ Lewis acid sites (LAS) and organic linker-linker, for example, hydrogen-bonding, interactions. Finally, the Lewis-acidic character of the Cu sites is illustrated by testing the films as catalysts in the isomerization of α-pinene oxide. The higher number of LAS (≥3000â rpm), result in higher campholenic aldehyde selectivity reaching up to 87.7 %. Furthermore, the strength of a combined micro- and spectroscopic approach in understanding the nature of MOF thin-films in a spatially resolved manner is highlighted.
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BACKGROUND: A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy. METHODS: Human chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression. RESULTS: Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin. CONCLUSION: Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.
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Gonadotropina Coriónica/sangre , Embarazo/sangre , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Adolescente , Adulto , Femenino , Humanos , Infertilidad Femenina/sangre , Persona de Mediana Edad , Valores de Referencia , Insuficiencia Renal Crónica/terapia , Adulto JovenRESUMEN
Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.
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Antiinfecciosos/uso terapéutico , Obstrucción del Catéter , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Diálisis Renal , Taurina/análogos & derivados , Tiadiazinas/uso terapéutico , Adulto , Anciano , Antiinfecciosos/efectos adversos , Antiinfecciosos/economía , Anticoagulantes/economía , Anticoagulantes/uso terapéutico , Austria , Obstrucción del Catéter/economía , Obstrucción del Catéter/etiología , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/economía , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/economía , Catéteres de Permanencia/efectos adversos , Catéteres de Permanencia/economía , Catéteres Venosos Centrales/efectos adversos , Catéteres Venosos Centrales/economía , Ahorro de Costo , Análisis Costo-Beneficio , Costos de los Medicamentos , Diseño de Equipo , Falla de Equipo , Femenino , Fibrinolíticos/economía , Fibrinolíticos/uso terapéutico , Heparina/economía , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal/economía , Factores de Riesgo , Taurina/efectos adversos , Taurina/economía , Taurina/uso terapéutico , Tiadiazinas/efectos adversos , Tiadiazinas/economía , Factores de Tiempo , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/economía , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.
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Prestación Integrada de Atención de Salud/organización & administración , Eficiencia Organizacional , Procedimientos Endovasculares , Fibrinolíticos/administración & dosificación , Grupo de Atención al Paciente/organización & administración , Regionalización/organización & administración , Accidente Cerebrovascular/terapia , Terapia Trombolítica , Tiempo de Tratamiento/organización & administración , Adulto , Anciano , Anciano de 80 o más Años , Vías Clínicas/organización & administración , Femenino , Alemania , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Transferencia de Pacientes/organización & administración , Evaluación de Programas y Proyectos de Salud , Mejoramiento de la Calidad/organización & administración , Indicadores de Calidad de la Atención de Salud/organización & administración , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Flujo de TrabajoRESUMEN
BACKGROUND: Isolated transient vertigo can be the only symptom of posterior circulation ischemia. Thus, it is important to differentiate isolated vertigo of a cerebrovascular origin from that of more benign origins, as patients with cerebral ischemia have a much higher risk for future stroke than do those with 'peripheral' vertigo. The current study aims to identify risk factors for cerebrovascular origin of isolated transient vertigo, and for future cerebrovascular events. METHODS: From the files of 339 outpatients with isolated transient vertigo we extracted history, clinical and technical findings, diagnosis, and follow-up information on subsequent stroke or transient ischemic attack (TIA). Risk factors were analyzed using multivariate regression models (logistic or Cox) and reconfirmed in univariate analyses. RESULTS: On first presentation, 48 (14.2%) patients received the diagnosis 'probable or definite cerebrovascular vertigo'. During follow-up, 41 patients suffered stroke or TIA (event rate 7.9 per 100 person years, 95% confidence interval (CI) 5.5-10.4), 26 in the posterior circulation (event rate 4.8 per 100 person years, 95% CI 3.0-6.7). The diagnosis was not associated with follow-up cerebrovascular events. In multivariate models testing multiple potential determinants, only the presentation mode was consistently associated with the diagnosis and stroke risk: patients who presented because of vertigo (rather than reporting vertigo when they presented for other reasons) had a significantly higher risk for future stroke or TIA (p = 0.028, event rate 13.4 vs. 5.4 per 100 person years) and for future posterior circulation stroke or TIA (p = 0.044, event rate 7.8 vs. 3.5 per 100 person years). CONCLUSIONS: We here report for the first time follow-up stroke rates in patients with transient isolated vertigo. In such patients, the identification of those with cerebrovascular origin remains difficult, and presentation mode was found to be the only consistent risk factor. Confirmation in an independent prospective sample is needed.
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Isquemia Encefálica/complicaciones , Ataque Isquémico Transitorio/complicaciones , Accidente Cerebrovascular/complicaciones , Vértigo/etiología , Anciano , Femenino , Humanos , Ataque Isquémico Transitorio/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: For an individual participant data (IPD) meta-analysis, multiple datasets must be transformed in a consistent format, e.g. using uniform variable names. When large numbers of datasets have to be processed, this can be a time-consuming and error-prone task. Automated or semi-automated identification of variables can help to reduce the workload and improve the data quality. For semi-automation high sensitivity in the recognition of matching variables is particularly important, because it allows creating software which for a target variable presents a choice of source variables, from which a user can choose the matching one, with only low risk of having missed a correct source variable. METHODS: For each variable in a set of target variables, a number of simple rules were manually created. With logic regression, an optimal Boolean combination of these rules was searched for every target variable, using a random subset of a large database of epidemiological and clinical cohort data (construction subset). In a second subset of this database (validation subset), this optimal combination rules were validated. RESULTS: In the construction sample, 41 target variables were allocated on average with a positive predictive value (PPV) of 34%, and a negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%, whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in 63% of all variables, in the validation sample in 71% of all variables. CONCLUSIONS: We demonstrated that the application of logic regression in a complex data management task in large epidemiological IPD meta-analyses is feasible. However, the performance of the algorithm is poor, which may require backup strategies.
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Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Bases de Datos Factuales , Factores Epidemiológicos , Modelos Logísticos , Aplicaciones de la Informática Médica , Algoritmos , Grosor Intima-Media Carotídeo , Minería de Datos , Humanos , Metaanálisis como Asunto , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND AND PURPOSE: In acute ischemic stroke, time from onset to tissue-type plasminogen activator treatment (OTT) is a major determinant of outcome. To reduce OTT, clinical trials have been undertaken evaluating prehospital cerebral imaging with mobile computed tomographic scanners. Furthermore, blood biomarkers may allow rapid differentiation between ischemic stroke and intracerebral hemorrhage before hospital admission. How such treatment strategies translate into clinical benefit has not been specifically evaluated. METHODS: We constructed decision models to estimate the net clinical benefit yielded by shorter OTT. In different scenarios, we estimated the proportion of patients with favorable outcome and the average quality of life. RESULTS: An OTT reduction of 60 minutes increases the probability of favorable outcome by 6.6% in a mixed stroke population. For comparison, the average effect of tissue-type plasminogen activator itself is 7.0%. Prehospital mobile computed tomography gaining 25 to 40 minutes increases the probability of favorable outcome by 3.0% to 4.6%. The additional benefit of prehospital computed tomography to deliver patients with large vessel occlusion directly to endovascular treatment centers increases the probability of favorable outcome by another 0.2% to 1.0%. A blood test discriminating ischemic stroke and intracerebral hemorrhage may beneficially substitute brain scan before tissue-type plasminogen activator if >32 to 40 minutes are gained and if sensitivity for intracerebral hemorrhage is >75% to 80%. CONCLUSIONS: Reducing the OTT has robust beneficial effects for acute stroke patients. Prehospital tissue-type plasminogen activator treatment without brain imaging may become conceivable under several preconditions, including a point-of-care test with >75% to 80% sensitivity to detect intracerebral hemorrhage and a time gain of >32 to 40 minutes. Ethical implications remain to be addressed.
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Isquemia Encefálica/tratamiento farmacológico , Servicios Médicos de Urgencia/métodos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/uso terapéutico , Benchmarking , Biomarcadores/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Hemorragia Cerebral/sangre , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Técnicas de Apoyo para la Decisión , Intervención Médica Temprana/métodos , Humanos , Sistemas de Atención de Punto , Calidad de Vida , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Terapia Trombolítica/métodos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%). METHODS: Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting. RESULTS: Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate (P=0.59) and severe stenosis (P=0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80-0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85-0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application. CONCLUSIONS: A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS.
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Estenosis Carotídea/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Estenosis Carotídea/epidemiología , Estenosis Carotídea/etiología , Femenino , Humanos , Estilo de Vida , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Riesgo , Fumar/efectos adversosRESUMEN
This paper reports on the advancement of a controlled-resonant surface tapping-mode single capillary liquid junction extraction/ESI emitter for mass spectrometry imaging. The basic instrumental setup and the general operation of the system were discussed, and optimized performance metrics were presented. The ability to spot sample, lane scan, and chemically image in an automated and controlled fashion were demonstrated. Rapid, automated spot sampling was demonstrated for a variety of compound types, including the cationic dye basic blue 7, the oligosaccharide cellopentaose, and the protein equine heart cytochrome c. The system was used for lane scanning and chemical imaging of the cationic dye crystal violet in inked lines on glass and for lipid distributions in mouse brain thin tissue sections. Imaging of the lipids in mouse brain tissue under optimized conditions provided a spatial resolution of approximately 35 µm based on the ability to distinguish between features observed both in the optical and mass spectral chemical images. The sampling spatial resolution of this system was comparable to the best resolution that has been reported for other types of atmospheric pressure liquid extraction-based surface sampling/ionization techniques used for mass spectrometry imaging.
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Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
BACKGROUND AND PURPOSE: Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. METHODS: We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. RESULTS: 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. CONCLUSIONS: In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.
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Trastornos de Deglución/etiología , Infarto de la Arteria Cerebral Media/complicaciones , Examen Neurológico/métodos , Sistemas de Atención de Punto , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Afasia/epidemiología , Afasia/etiología , Apraxias/epidemiología , Apraxias/etiología , Tos , Deglución , Trastornos de Deglución/epidemiología , Dominancia Cerebral , Tecnología de Fibra Óptica , Atragantamiento , Humanos , Laringoscopía , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reflejo Anormal , Medición de Riesgo , Sensibilidad y Especificidad , Calidad de la Voz , VoliciónRESUMEN
RATIONALE: Laser ablation provides for the possibility of sampling a large variety of surfaces with high spatial resolution. This type of sampling when employed in conjunction with liquid capture followed by nanoelectrospray ionization provides the opportunity for sensitive and prolonged interrogation of samples by mass spectrometry as well as the ability to analyze surfaces not amenable to direct liquid extraction. METHODS: A fully automated, reflection geometry, laser ablation liquid capture spot sampling system was achieved by incorporating appropriate laser fiber optics and a focusing lens into a commercially available, liquid extraction surface analysis (LESA(®))-ready Advion TriVersa NanoMate system. RESULTS: Under optimized conditions about 10% of laser-ablated material could be captured in a droplet positioned vertically over the ablation region using the NanoMate robot-controlled pipette. The sampling spot size area with this laser ablation liquid capture surface analysis (LA/LCSA) mode of operation (typically about 120 µm × 160 µm) was approximately 50 times smaller than that achievable by direct liquid extraction using LESA(®) (ca 1 mm diameter liquid extraction spot). The setup was successfully applied for the analysis of ink on glass and paper as well as the endogenous components in Alstroemeria Yellow King flower petals. In a second mode of operation with a comparable sampling spot size, termed laser ablation/LESA(®), the laser system was used to drill through, penetrate, or otherwise expose material beneath a solvent resistant surface. Once drilled, LESA(®) was effective in sampling soluble material exposed at that location on the surface. CONCLUSIONS: Incorporating the capability for different laser ablation liquid capture spot sampling modes of operation into a LESA(®)-ready Advion TriVersa NanoMate enhanced the spot sampling spatial resolution of this device and broadened the surface types amenable to analysis to include absorbent and solvent-resistant materials.
RESUMEN
RATIONALE: Capture of material from a laser ablation plume into a continuous flow stream of solvent provides the means for uninterrupted sampling, transport and ionization of collected material for coupling with mass spectral analysis. Reported here is the use of vertically aligned transmission geometry laser ablation in combination with a new non-contact liquid vortex capture probe coupled with electrospray ionization for spot sampling and chemical imaging with mass spectrometry. METHODS: A vertically aligned continuous flow liquid vortex capture probe was positioned directly underneath a sample surface in a transmission geometry laser ablation (355 nm, 10 Hz, 7 ns pulse width) set up to capture into solution the ablated material. The outlet of the vortex probe was coupled to the Turbo V™ ion source of an AB SCIEX TripleTOF 5600+ mass spectrometer. System operation and performance metrics were tested using inked patterns and thin tissue sections. Glass slides and slides designed especially for laser capture microdissection, viz., DIRECTOR(®) slides and PEN 1.0 (polyethylene naphthalate) membrane slides, were used as sample substrates. RESULTS: The estimated capture efficiency of laser-ablated material was 24%, which was enabled by the use of a probe with large liquid surface area (~2.8 mm(2) ) and with gravity to help direct ablated material vertically down towards the probe. The swirling vortex action of the liquid surface potentially enhanced capture and dissolution not only of particulates, but also of gaseous products of the laser ablation. The use of DIRECTOR(®) slides and PEN 1.0 (polyethylene naphthalate) membrane slides as sample substrates enabled effective ablation of a wide range of sample types (basic blue 7, polypropylene glycol, insulin and cyctochrome c) without photodamage using a UV laser. Imaging resolution of about 6 µm was demonstrated for stamped ink on DIRECTOR(®) slides based on the ability to distinguish features present both in the optical and in the chemical image. This imaging resolution was 20 times better than the previous best reported results with laser ablation/liquid sample capture mass spectrometry imaging. Using thin sections of brain tissue the chemical image of a selected lipid was obtained with an estimated imaging resolution of about 50 µm. CONCLUSIONS: A vertically aligned, transmission geometry laser ablation liquid vortex capture probe, electrospray ionization mass spectrometry system provides an effective means for spatially resolved spot sampling and imaging with mass spectrometry.