Natural history of swallow function during the three-month period after stroke

Oropharyngeal dysphagia is a prevalent complication following stroke (PS-OD), and one that is sometimes spontaneously recovered. This study describes the natural history of PS-OD between admission and three months post-stroke, and the factors associated with its prevalence and development. PS-OD was assessed with the volume- iscosity swallow test (V-VST) in all stroke patients on admission and at the three-month follow-up. We analyzed clinical, demographic, and neuroanatomical factors of 247 older post-stroke patients (National Institute of Health Stroke Scale (NIHSS) = 3.5 ± 3.8), comparing among those with PS-OD the ones with and without spontaneous recovery. PS-OD prevalence on admission was 39.7% (34.0% impaired safety; 30.8%, efficacy) and 41.7% (19.4% impaired safety; 39.3%, efficacy) at three months. Spontaneous swallow recovery occurred in 42.4% of patients with unsafe and in 29.9% with ineffective swallow, associated with younger age and optimal functional status. However, 26% of post-stroke patients developed new signs/symptoms of ineffective swallow related to poor functional, nutritional and health status, and institutionalization. PS-OD prevalence on admission and at the three-month follow-up was very high in the study population. PS-OD is a dynamic condition with some spontaneous recovery in patients with optimal functional status, but also new signs/symptoms can appear due to poor functionality. Regular PS-OD monitoring is needed to identify patients at risk of nutritional and respiratory complications

RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Background: Around 15-20% of primary breast cancers are characterized by HER2 protein overexpression and/or HER2 gene amplification. Despite the successful development of anti-HER2 drugs, intrinsic and acquired resistance represents a major hurdle. This study was performed to analyze the RANK pathway contribution in HER2-positive breast cancer and anti-HER2 therapy resistance. Methods: RANK and RANKL protein expression was assessed in samples from HER2-positive breast cancer patients resistant to anti-HER2 therapy and treatment-naive patients. RANK and RANKL gene expression was analyzed in paired samples from patients treated with neoadjuvant dual HER2-blockade (lapatinib and trastuzumab) from the SOLTI-1114 PAMELA trial. Additionally, HER2-positive breast cancer cell lines were used to modulate RANK expression and analyze in vitro the contribution of RANK signaling to anti-HER2 resistance and downstream signaling. Results: RANK and RANKL proteins are more frequently detected in HER2-positive tumors that have acquired resistance to anti-HER2 therapies than in treatment-naive ones. RANK (but not RANKL) gene expression increased after dual anti-HER2 neoadjuvant therapy in the cohort from the SOLTI-1114 PAMELA trial. Results in HER2-positive breast cancer cell lines recapitulate the clinical observations, with increased RANK expression observed after short-term treatment with the HER2 inhibitor lapatinib or dual anti-HER2 therapy and in lapatinib-resistant cells. After RANKL stimulation, lapatinib-resistant cells show increased NF-κB activation compared to their sensitive counterparts, confirming the enhanced functionality of the RANK pathway in anti-HER2-resistant breast cancer. Overactivation of the RANK signaling pathway enhances ERK and NF-κB signaling and increases lapatinib resistance in different HER2-positive breast cancer cell lines, whereas RANK loss sensitizes lapatinib-resistant cells to the drug. Our results indicate that ErbB signaling is required for RANK/RANKL-driven activation of ERK in several HER2-positive cell lines. In contrast, lapatinib is not able to counteract the NF-κB activation elicited after RANKL treatment in RANK-overexpressing cells. Finally, we show that RANK binds to HER2 in breast cancer cells and that enhanced RANK pathway activation alters HER2 phosphorylation status. Conclusions: Our data support a physical and functional link between RANK and HER2 signaling in breast cancer and demonstrate that increased RANK signaling may contribute to the development of lapatinib resistance through NF-κB activation. Whether HER2-positive breast cancer patients with tumoral RANK expression might benefit from dual HER2 and RANK inhibition therapy remains to be elucidated

Comparison of the impact of atrial fibrillation on the risk of early death after stroke in women versus men

BACKGROUND: Atrial fibrillation (AF) is considered a predictive factor of poor clinical outcome in patients with an ischemic stroke (IS). This study addressed whether the impact of AF on the in-hospital mortality after first ever IS is different according to the patient’s gender. METHODS: We prospectively studied 1678 patients with first ever IS consecutively admitted to two University Hospitals. We recorded demographic data, vascular risk factors, and the stroke severity (NIHSS) at admission analyzing their impact on the in-hospital mortality and on the combined mortality-dependency at discharge using a Cox proportional hazards model. Two variable interactions between those factors independently related to in-hospital mortality and combined mortality-dependency at discharge were tested. RESULTS: Overall in-hospital mortality was 11.3%. Cox proportional hazards model showed that NIHSS at admission (HR: 1.178 [95% CI 1.149–1.207]), age (HR: 1.044 [95% CI 1.026–1.061]), AF (HR: 1.416 [95% CI 1.048–1.913]), male gender (HR: 1.853 [95% CI 1.323–2.192) and ischemic heart disease (HR: 1.527 [95% CI 1.063–2.192]) were independent predictors of in-hospital mortality. A significant interaction between gender and AF was found (p = 0.017). Data were stratified by gender, showing that AF was an independent predictor of poor outcome just for woman (HR: 2.183 [95% CI 1.403–3.396]; p < 0.001). The independent predictors of combined mortality-disability at discharge were NIHSS at admission (HR: 1.052 [95% CI 1.041–1.063]), age (HR: 1.011 [95% CI 1.004–1.018]), AF (HR: 1.197 [95% CI 1.031–1.390]), ischemic heart disease (HR: 1.222 [95% CI 1.004–1.488]), and smoking (HR: 1.262 [95% CI 1.033–1.541]). CONCLUSIONS: The impact of AF is different in the twogenders and appears as a specific ischemic stroke predictor of in-hospital mortality just for women

Variables associades al temps d'arribada a l'hospital en els pacients amb un ictus a la comarca del Maresme

Consultable des del TDXTítol obtingut de la portada digitalitzadaIntroducció Una ràpida arribada a urgències millora el pronòstic dels pacients amb un ictus. Per això cada vegada creix més la importància d'escurçar els temps de latència, així com d'analitzar el coneixement que té la població sobre la malaltia, sobretot la seva percepció d'urgència. La variabilitat en la metodologia dels diferents estudis que avaluen aquests aspectes, així com les diferències socioculturals i geogràfiques de cada país fa difícil extrapolar les seves conclusions. Objectius Analitzar els temps de demora extrahospitalària en els pacients amb un ictus a la comarca del Maresme (Barcelona). Valorar el coneixement que té la població sobre l'ictus i la seva percepció d'urgència. Analitzar els factors que influeixen en la demora extrahospitalària en els pacients amb un ictus. Material i métode Estudi prospectiu que ha inclòs tots els pacients ingressats amb un ictus a la nostra Unitat durant un any consecutiu, excloent aquells que procedien d'altres hospitals, els que presentaven l'ictus a l'hospital o els que no podien col·laborar a l'anamnesi. El protocol de recollida de dades constava de 76 variables, entre elles un breu qüestionari sobre el reconeixement dels seus símptomes i la actitud immediata davant els mateixos. S'ha realitzat un estudi descriptiu i una anàlisi estadística univariant i multivariant per una demora inferior o superior a 3 hores. Es repeteix l'estudi per una demora inferior o superior a 1 hora. Resultats S'inclouen a l'estudi 292 pacients. D'ells, un 18.8% va arribar a urgències abans d'1 hora des de l'inici dels símptomes i un 57.5% abans de 3 hores. Un 34.4% va reconéixer els seus símptomes com un ictus i un 31.8% va decidir anar immediatament a urgències. Les variables associades de forma independent amb demora <3 hores són: percepció d'urgència (OR 8.17, p:0.000), arribar en ambulància (OR 2.35, p:0.002), infart tipus TACI (OR 3.74, p:0.004) i tenir menys de 2 factors de risc vascular (OR 0.47, p:0.014). S'associen a demora <1 hora la percepció d'urgència (OR 3.55, p:0.000), ictus en diumenge (OR 3.46, p:0.002), afectació del llenguatge (OR 2.41, p:0.011), no tenir escales a la llar (OR 0.37, p:0.012), i no ser diabètic (OR 0.42, p:0.021). Conclusions A la nostra àrea d'influència, més de la meitat dels pacients amb un ictus arriben abans de 3 hores. Només 1/3 dels pacients interpreten correctament els seus símptomes, i menys d'1/3 tenen percepció d'urgència. Els factors associats de forma independent a una demora inferior a 3 hores són: percepció d'urgència, arribar en ambulància, infart tipus TACI i tenir menys de 2 factors de risc vascular. La percepció d'urgència es la variable més potent associada a una arribada ultrarràpida, però no la utilització de l'ambulància. Per tant, el missatge a transmetre és que davant d'un ictus el més important és traslladar-lo ràpidament a l'hospital, sigui en cotxe particular o en ambulància.Background An early arrival to emergency service improves outcome of stroke patients. There's an increasing need to shorten the extrahospitalary delay and also to analyze the knowledge of stroke among the population, and their perception as an emergency. The methodology of the studies is quite different, and there are cultural and geographic differences among the countries where they've been made, so it's difficult to generalize the conclusions. Objective To analyze the delay between the onset of symptoms and arrival at emergency service in patients who suffer a stroke in Maresme region (Barcelona). To study knowledge of stroke among the population, and their perception as an emergency. To analyze which factors are related to the delay in hospital admission in these patients. Methods It's a prospective study including all the patients admitted in our Unit with a diagnosis of stroke within a 1-year period. Patients coming from another hospital and those who suffered a stroke in the hospital were excluded. If anamnesis was not possible, patient was also excluded. Seventy-six data were analyzed, with a brief questionnaire about recognition of symptoms and attitude towards them. After a descriptive study, an univariate and multivariate analysis has been done to know which factors are related to an arrival within 3 hours and, after next, to analyze arrival within 1 hour. Results Two hundred and twenty-two consecutive patients were included. Eighteen percent of them arrived to emergency room before than 1 hour from symptoms onset , and 57.5% before than 3 hours. Only 34.4% knew they were having a stroke and 31.8% went immediately to hospital. Perception of symptoms as an emergency (OR 8.17, p:0.000), use of ambulance (OR 2.35, p:0.002), TACI infarct (OR 3.74, p:0.004) and having less than 2 vascular risk factors (OR 0.47, p:0.014) are associated with an arrival within 3 hours in logistic regression analysis. Perception of symptoms as an emergency (OR 3.55, p:0.000), suffering the stroke on sunday (OR 3.46, p:0.002), speech disturbance (OR 2.41, p:0.011), not having stairs at home (OR 0.37, p:0.012) and not having diabetes (OR 0.42, p:0.021) are associated with an arrival within 1 hour. Conclusions In our region, more than half of stroke patients arrive to hospital within 3 hours after symptoms onset. Only 1/3 of patients recognize their symptoms as a stroke and less than 1/3 perceive them as an emergency. Factors associated with a delay less than 3 hours are: perception of stroke as an emergency, use of ambulance, TACI infarct and having less than 2 vascular risk factors. Perception of stroke as an emergency is the most powerful variable associated with a very quick time to presentation, but not the use of ambulance. So, in the presence of a stroke, the most important action is going to the hospital, either by car or ambulance

The Mataró Stroke Registry: A 10-year registry in a community hospital

Introduction: A prospective stroke registry leads to improved knowledge of the disease. We present data on the Mataró Hospital Registry. Methods: In February 2002 a prospective stroke registry was initiated in our hospital. It includes sociodemographic data, previous diseases, and clinical, topographic, aetiological and prognostic data. We have analysed the results of the first 10 years. Results: A total of 2165 patients have been included, 54.1% male, mean age 73 years. The most frequent vascular risk factor was hypertension (65.4%). Median NIHSS on admission: 3 (interquartile range, 1–8). Stroke subtype: 79.7% ischaemic strokes, 10.9% haemorrhagic, and 9.4% TIA. Among ischaemic strokes, the aetiology was cardioembolic in 26.5%, large-vessel disease in 23.7%, and small-vessel in 22.9%. The most frequent topography of haemorrhages was lobar (47.4%), and 54.8% were attributed to hypertension. The median hospital stay was 8 days. At discharge, 60.7% of the patients were able to return directly to their own home, and 52.7% were independent for their daily life activities. After 3 months these percentages were 76.9% and 62.9%, respectively. Hospital mortality was 6.5%, and after 3 months it was 10.9%. Conclusions: Our patient's profile is similar to those of other series, although the severity of strokes was slightly lower. Length of hospital stay, short-term and medium-term disability, and mortality rates are good, if we compare them with other series. Resumen: Introducción: Un registro prospectivo de ictus permite mejorar el conocimiento de la historia natural de la enfermedad. Presentamos los datos del Registro del Hospital de Mataró. Métodos: En febrero de 2002 se inició en nuestro hospital el registro prospectivo de pacientes ingresados con un ictus agudo. Se recogen variables sociodemográficas, antecedentes, clínicas, topográficas, etiológicas y pronósticas. Analizamos los resultados obtenidos después de los primeros 10 años de registro. Resultados: Se han registrado 2.165 pacientes, el 54,1% varones, con una edad media de 73 años. El factor de riesgo más frecuente es la hipertensión (65,4%). Mediana de la NIHSS al ingreso: 3 (rango intercuartílico, 1–8). Un 79,7% han sido infartos cerebrales, un 10,9% hemorragias y un 9,4% AIT. De los isquémicos, la etiología ha sido cardioembólica en el 26,5%, aterotrombótica en el 23,7% y lacunar en el 22,9%. La localización más frecuente de las hemorragias ha sido lobar (47,4%), y se han atribuido a hipertensión el 54,8%. La mediana de la estancia hospitalaria ha sido de 8 días. Al alta, un 60,7% pudieron volver directamente al domicilio y un 52,7% eran independientes para las actividades de la vida diaria. A los 3 meses, las cifras fueron 76,9 y 62,9% respectivamente. La mortalidad intrahospitalaria ha sido del 6,5% y a los 3 meses del 10,9%. Conclusiones: El perfil de los pacientes en nuestra área no difiere de las otras series, aunque la severidad de los ictus ha sido discretamente menor. Constatamos unas cifras óptimas de estancia hospitalaria y de discapacidad y mortalidad tanto a corto como a medio plazo. Keywords: Stroke, Stroke registry, Epidemiology, Prognosis, Outcome, Cerebrovascular disease, Palabras clave: Ictus, Registro de ictus, Epidemiología, Pronóstico, Evolución, Enfermedad cerebrovascula

Rapid assessment of transient ischaemic attack in a hospital with no on-call neurologist

Background: Risk of stroke soon after a transient ischaemic attack (TIA) is high. Urgent care can reduce this risk. Our aim is to describe and evaluate the efficacy of rapid assessment of TIA patients in a hospital without a neurologist available 24 h a day. Methods: In February 2007, we set up a protocol of rapid management of patients with symptoms consistent with acute TIA, with the aim of prioritising urgent care and reducing hospital admissions, without increasing risk of recurrences. We analyse our results since the protocol was implemented with particular focus on the analysis of delay in neurological and neurovascular assessment, percentage and reasons for hospitalisation, and stroke recurrence rates after 3 months. Results: Four hundred and eleven patients were studied, with a final diagnosis of TIA in 282 (68.6%). Among other diagnoses, the most frequent were a vasovagal reaction (5.6%), and a confusional syndrome (4.6%). Delay between emergency arrival and neurovascular assessment was <24 h in 82% of cases, and <48 h in 93%. After neurological evaluation, 28.7% of the patients were immediately admitted to hospital (most common causes: severe stenosis of a large artery and crescendo TIA). The incidence of ischaemic stroke in TIA patients was 3.55% after 3 months, and 70% of them suffered the recurrence within the first week after the initial TIA. Conclusions: In a hospital without a neurologist available 24 h a day, an early assessment and management of TIA patients can be carried out in accordance with the guidelines, and may avoid hospitalisation in most cases without increasing recurrence rates. Resumen: Introducción: Los pacientes que presentan un ataque isquémico transitorio (AIT) tienen un alto riesgo de tener un ictus a corto plazo. Una atención urgente puede reducir dicho riesgo. El objetivo es describir y comprobar la eficacia de un protocolo de atención rápida a estos pacientes en un hospital sin guardias de neurología. Métodos: En febrero del 2007 se puso en marcha en nuestro hospital un protocolo de evaluación rápida del AIT, con el objetivo de priorizar la atención urgente y disminuir ingresos hospitalarios sin aumentar riesgo de recurrencias. Se analizan los resultados tras los primeros 5 años, incidiendo especialmente en los tiempos de valoración neurológica y neurovascular, motivos de ingreso y tasa de recurrencia a los 90 días. Resultados: Han sido evaluados 411 pacientes, de los cuales 282 (68,6%) fueron finalmente AIT. Entre los otros diagnósticos, los más frecuentes han sido el episodio vasovagal (5,6%) y el cuadro confusional (4,6%). La demora entre la llegada a Urgencias y la valoración del neurólogo fue <24 h en el 82% de casos y <48 h en el 93,9%. Tras la valoración neurológica, se decidió el ingreso en el 28,7% de pacientes (causas más frecuentes: hallazgos en el Doppler y AIT de repetición). A los 3 meses, 10 pacientes (3,55%) presentaron un ictus, 7 de ellos (70%) en la primera semana desde el episodio. Conclusiones: En un hospital sin guardias de neurología, es posible una evaluación rápida de los pacientes con AIT, de acuerdo con las recomendaciones de las guías, evitando la mayoría de ingresos y con un bajo índice de recurrencias. Keywords: Transient ischaemic attack, Stroke, Recurrence, Urgent care, Management, Prognosis, Palabras clave: Ataque isquémico transitorio, Ictus, Recurrencia, Atención urgente, Gestión, Pronóstic