RESUMEN
Purpose: Post-stroke dysphagia is an underdiagnosed but relevant complication, associated with worse outcome, dependency and quality of life of stroke survivors. Detailed mechanisms of post-stroke dysphagia are not very well understood, but established therapeutic concepts are needed. Different interventional studies have been published dealing with post-stroke dysphagia. This systematic review wants to collect and give an overview over the published evidence. Methods: PubMed, Embase, Cochrane, CINAHL were searched for relevant interventional studies on post-stroke dysphagia in the (sub-)acute setting (within 3 months of stroke onset). The search has been filtered for randomized trials with an inactive control and the relevant data extracted. Results: After initially finding 2,863 trials, finally 41 trials have been included. Seven different therapeutic concepts have been evaluated (Acupuncture, behavioral/physical therapy, drug therapy, neuromuscular electrical stimulation, pharyngeal electrical stimulation, transcranial direct current stimulation and repetitive transcranial magnetic stimulation). Studies of all modalities have shown some effect on post-stroke dysphagia with several studies raising concerns about the potential bias. Conclusion: The amount and quality of studies are not enough to suggest certain therapies. Some therapeutical concepts (intensive physical therapy, transcranial magnetic stimulation, drug therapy) seem to be good potential therapeutic options, but further research is needed.
RESUMEN
The objective of this study was to quantify enzymatic activity on the surface of T cells by magnetic resonance imaging (MRI) using R2 and R2* relaxometry. Lymphoma cells expressing adenosine diphosphate (ADP)-ribosyltransferase 2 (ART2) were incubated with increasing doses of its substrate etheno-nicotinamide adenine dinucleotide (NAD), resulting in increasing amounts of surface protein ADP-ribosylation. Etheno-ADP-ribosylated proteins were detected with monoclonal antibody 1G4 and superparamagnetic iron oxide conjugated secondary antibodies (Ab-SPIO). Labeling efficiency was determined with R2 and R2* relaxometry on a clinical 3.0 T scanner. Parallel aliquots of cells were analyzed by flow cytometry. Cell-bound SPIO conjugates were detected by immunofluorescence and electron microscopy and quantified by atomic absorption spectroscopy. To mimic an inflammatory site in vivo, Ab-SPIO-labeled cells were injected subcutaneously in mice and analyzed by MRI. Immunofluorescence and electron microscopy confirmed cell-surface localization of Ab-SPIO. MRI of Ab-SPIO-labeled cells showed a corresponding signal reduction. Increases in R2 and R2* determined by magnetic resonance relaxometry correlated linearly with the expression level of ART2 and the concentration of the ART2 substrate etheno-NAD. R2 and R2* increases correlated linearly with the results from flow cytometry and atomic absorption spectroscopy analyses. Quantitative R2 and R2* mapping enable noninvasive determination of enzymatic activity on T cells and holds promise for characterization of inflammatory sites in vivo by MRI.
Asunto(s)
ADP Ribosa Transferasas/metabolismo , Membrana Celular/enzimología , Compuestos Férricos/metabolismo , Imagen por Resonancia Magnética/métodos , Linfocitos T/enzimología , Adenosina Difosfato Ribosa/metabolismo , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Línea Celular Tumoral , Compuestos Férricos/química , Citometría de Flujo , Modelos Lineales , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , NAD/metabolismo , NAD/farmacología , Reproducibilidad de los Resultados , Imagen de Cuerpo EnteroRESUMEN
Importance: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. Objective: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. Design, Setting, and Participants: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. Exposures: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). Main Outcomes and Measures: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. Results: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. Conclusions and Relevance: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.