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1.
Eur J Neurol ; 28(12): 4078-4089, 2021 12.
Article in English | MEDLINE | ID: mdl-34528353

ABSTRACT

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.


Subject(s)
COVID-19 , Stroke , COVID-19 Testing , Cohort Studies , Humans , Retrospective Studies , SARS-CoV-2 , Stroke/epidemiology
2.
Stroke ; 52(2): 552-562, 2021 01.
Article in English | MEDLINE | ID: mdl-33406872

ABSTRACT

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks/prevention & control , SARS-CoV-2/pathogenicity , Stroke/epidemiology , Stroke/virology , Aged , Aged, 80 and over , COVID-19/complications , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Retrospective Studies
4.
Neurology ; 92(21): e2432-e2443, 2019 05 21.
Article in English | MEDLINE | ID: mdl-31004066

ABSTRACT

OBJECTIVE: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI. METHODS: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses. RESULTS: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4). CONCLUSION: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.


Subject(s)
Anticoagulants/therapeutic use , Cerebral Small Vessel Diseases/epidemiology , Intracranial Embolism/prevention & control , Intracranial Hemorrhages/epidemiology , Stroke/prevention & control , Aged , Aged, 80 and over , Cerebral Small Vessel Diseases/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Multivariate Analysis , Proportional Hazards Models , Prospective Studies , Risk Assessment
5.
J Stroke Cerebrovasc Dis ; 27(11): 3289-3293, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30172679

ABSTRACT

OBJECTIVES: To describe the neurological manifestations of invasive aspergillosis presenting with a focal neurological deficit compatible with an acute stroke. MATERIALS AND METHODS: Retrospective analysis of a clinical series of patients between 2011 and 2017 with invasive aspergillosis and neurological symptoms compatible with an acute brain stroke. Clinical and epidemiological data, microbiological results, radiological findings, treatment, and course were recorded. RESULTS: Five patients were selected with a mean age of 55.4years. All patients were immunosuppressed. In 4, systemic infection was unknown. In every case, neurology on call was alerted because of acute focal neurological symptoms. None of the patients received revascularization procedures. Galactomannan antigen was positive in all of the patients and culture was positive in 3. Mortality was 100% despite specific antifungal treatment. CONCLUSIONS: Acute stroke can be the first manifestation of disseminated aspergillosis. This form of presentation was frequent in our series and should be suspected in immunocompromised patients with acute neurological deficits.


Subject(s)
Neuroaspergillosis/microbiology , Opportunistic Infections/microbiology , Stroke/microbiology , Antifungal Agents/therapeutic use , Autopsy , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Magnetic Resonance Imaging , Male , Middle Aged , Neuroaspergillosis/diagnosis , Neuroaspergillosis/immunology , Neuroaspergillosis/mortality , Opportunistic Infections/diagnosis , Opportunistic Infections/immunology , Opportunistic Infections/mortality , Retrospective Studies , Risk Factors , Spain , Stroke/diagnostic imaging , Stroke/immunology , Stroke/mortality , Treatment Outcome
6.
Sci Rep ; 8(1): 1492, 2018 01 24.
Article in English | MEDLINE | ID: mdl-29367736

ABSTRACT

We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 ± 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pre-treatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected.


Subject(s)
Anticoagulants/therapeutic use , Biomarkers/analysis , Cerebral Hemorrhage/pathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intracranial Embolism/complications , Stroke/complications , Aged , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/metabolism , Female , Humans , Intracranial Embolism/drug therapy , Male , Prognosis , Prospective Studies , Stroke/drug therapy
7.
Rev Neurol ; 62(7): 303-10, 2016 Apr 01.
Article in Spanish | MEDLINE | ID: mdl-26988168

ABSTRACT

INTRODUCTION: A stroke is a time-dependent medical emergency. Swiftness in its recognition and in the care received by the patients plays a key role in the prognosis. AIMS: To analyse the medical intervention times, to evaluate possible areas where improvements can be made and to examine the allocation of resources in the centres. PATIENTS AND METHODS: The study was based on a prospective register of patients with suspected stroke and stroke code activation treated in eight experienced Spanish stroke units. Onset-to-door, door-to-computed tomography (CT), door-to-needle, CT-to-needle and onset-to-needle times were collected. Information about the means of transport used to get to the hospital, the type of stroke and reperfusion therapies was also collected. With regard to the structural resources of the centres, data were gathered about the nurse-to-patient ratio, bed monitoring, availability of multimodal CT and magnetic resonance, and doing information or training courses. RESULTS: Altogether 197 patients were included, of whom 181 (151 infarctions and 30 brain haemorrhages) were valid. The medians (p25-p75) in minutes were: onset-to-door, 104 (70-188); door-to-CT, 27 (19-41); CT-to-needle, 30 (21-43); door-to-needle, 64 (49-83); and onset-to-needle, 156 (129-202). Reperfusion therapies were applied in 68 patients (45% of the cerebral infarctions), of which 81% were intravenous thrombolyses; 7%, endovascular treatments; and 12%, a combination of the two. The resources available in the centres were in accordance with those recommended by the clinical guidelines. There was a low percentage of patients who were studied by means of magnetic resonance. CONCLUSION: The percentage of patients treated with thrombolysis was very high and although the times of the in-hospital circuits were good, there is still room for further improvement.


TITLE: Atencion urgente al ictus en hospitales con unidad de ictus. Proyecto Quick.Introduccion. El ictus es una emergencia medica dependiente del tiempo. La rapidez en su reconocimiento y en la atencion que reciben los pacientes es clave en el pronostico. Objetivos. Analizar los tiempos de actuacion medica, evaluar posibles areas de mejora y estudiar la dotacion de recursos de los centros. Pacientes y metodos. Registro prospectivo de pacientes atendidos en ocho unidades de ictus experimentadas españolas con sospecha de ictus y activacion del codigo ictus. Se recogieron los tiempos inicio-puerta, puerta-tomografia computarizada (TC), puerta-aguja, TC-aguja e inicio-aguja. Tambien se recogieron el metodo de trasporte al hospital, el tipo de ictus y las terapias de reperfusion. En cuanto a la dotacion estructural de los centros, se recogieron la ratio de enfermeria, la monitorizacion de camas, la disponibilidad de TC multimodal y resonancia magnetica, y la realizacion de cursos de informacion o formacion. Resultados. Se incluyeron 197 pacientes, de los cuales fueron validos 181 (151 infartos y 30 hemorragias cerebrales). Las medianas (p25-p75) en minutos fueron: inicio-puerta, 104 (70-188); puerta-TC, 27 (19-41); TC-aguja, 30 (21-43); puerta-aguja, 64 (49-83); e inicio-aguja, 156 (129-202). Se aplicaron terapias de reperfusion en 68 pacientes (el 45% de los infartos cerebrales), de los cuales el 81% fueron trombolisis intravenosas; el 7%, tratamientos endovasculares; y el 12%, una combinacion de ambos. Los recursos de los centros estuvieron de acuerdo con lo recomendado por las guias clinicas. Hubo un bajo porcentaje de pacientes estudiados con resonancia magnetica. Conclusion. El porcentaje de pacientes tratados con trombolisis fue muy elevado y los tiempos de los circuitos intrahospitalarios, aunque buenos, tienen margen de mejora.


Subject(s)
Ambulatory Care/statistics & numerical data , Hospital Units/statistics & numerical data , Stroke/drug therapy , Thrombolytic Therapy/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Clinical Coding/statistics & numerical data , Emergencies , Emergency Medical Services/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Magnetic Resonance Imaging , Patient Transfer/statistics & numerical data , Prospective Studies , Spain/epidemiology , Stroke/diagnostic imaging , Stroke/epidemiology , Tomography, X-Ray Computed
11.
Rev Neurol ; 59(1): 25-36, 2014 Jul 01.
Article in Spanish | MEDLINE | ID: mdl-24965928

ABSTRACT

Atrial fibrillation is the most frequent arrhythmia seen in clinical practice and is one of the most important risk factors for suffering a stroke. Strokes associated to atrial fibrillation are more severe, present higher mortality and disability rates, and there is a greater risk of recurrence. Consequently, both primary and secondary prevention of stroke associated to atrial fibrillation by means of suitable antithrombotic treatment is clearly essential in order to lower this risk. Chronic oral anticoagulants are the cornerstone of antithrombotic treatment in patients with non-valvular atrial fibrillation, especially in those who have already had a stroke. Vitamin K antagonists have traditionally been used for this purpose. Yet, these drugs have several important disadvantages (narrow therapeutic window, unpredictable response, numerous interactions with drugs and foods, as well as starting and finishing their action slowly), which limit their use in clinical practice. The new oral anticoagulants not only overcome these disadvantages but also have proved to be at least as effective as warfarin in the prevention of strokes and systemic embolism in patients with non-valvular atrial fibrillation. Additionally, they have been shown to have a better safety profile, especially with an important drop in the risk of intracranial haemorrhage, regardless of the antecedents of stroke or transient ischaemic attack, which makes them first-choice drugs in the treatment of these patients.


TITLE: Manejo actual del tratamiento antitrombotico en pacientes con fibrilacion auricular no valvular y antecedentes de ictus o ataque isquemico transitorio.La fibrilacion auricular es la arritmia mas frecuente en la practica clinica y es uno de los factores de riesgo mas importantes para padecer un ictus. Los ictus asociados a la fibrilacion auricular son mas graves, presentan una mayor mortalidad y discapacidad, y el riesgo de recurrencias es mayor. En consecuencia, la prevencion, tanto primaria como secundaria, del ictus asociado a la fibrilacion auricular mediante el adecuado tratamiento antitrombotico es claramente esencial y crucial para disminuir este riesgo. La anticoagulacion oral cronica supone la piedra angular del tratamiento antitrombotico en el paciente con fibrilacion auricular no valvular, especialmente en el paciente que ya ha tenido un ictus. Para este fin, tradicionalmente se han empleado los antagonistas de la vitamina K. Sin embargo, estos farmacos poseen importantes desventajas (estrecha ventana terapeutica, respuesta impredecible, numerosas interacciones con farmacos y alimentos, asi como un comienzo y final de accion lentos) que limitan su uso en la practica clinica. Los nuevos anticoagulantes orales no solo superan estas desventajas, sino que, ademas, han demostrado ser, al menos, tan eficaces como la warfarina en la prevencion de ictus y embolia sistemica en los pacientes con fibrilacion auricular no valvular, y poseer un mejor perfil de seguridad, en particular con una importante disminucion del riesgo de hemorragia intracraneal, independientemente de los antecedentes de ictus o ataque isquemico transitorio, lo que hace que sean farmacos de primera linea en el tratamiento de estos pacientes.


Subject(s)
Atrial Fibrillation/complications , Fibrinolytic Agents/therapeutic use , Intracranial Embolism/prevention & control , Ischemic Attack, Transient/etiology , Stroke/etiology , Thrombophilia/drug therapy , Administration, Oral , Clinical Trials as Topic , Disease Management , Drugs, Investigational/therapeutic use , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/classification , Follow-Up Studies , Hemorrhage/chemically induced , Humans , Intracranial Embolism/etiology , Ischemic Attack, Transient/prevention & control , Multicenter Studies as Topic , Prognosis , Recurrence , Risk Factors , Secondary Prevention , Stroke/prevention & control , Thrombophilia/etiology
12.
J Child Neurol ; 29(2): 269-73, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24272519

ABSTRACT

We report the case of a healthy 12-year-old girl with an acute ischemic stroke successfully treated with mechanical thrombectomy. The child was referred to our hospital 6 hours after sudden onset of severe headache and left hemiparesis. Cerebral angiography findings were consistent with right distal internal carotid artery occlusion in addition to ipsilateral middle cerebral artery occlusion. Subsequent mechanical thrombectomy with Solitaire AB device resulted in complete vessel recanalization. The patient experienced progressive neurologic improvement with good clinical recovery at the 3-month follow-up. To our knowledge, only 3 cases of primary mechanical thrombectomy in children have been previously reported in the literature. Safety and efficacy data for endovascular therapies in pediatric acute ischemic stroke are lacking. We propose mechanical thrombectomy as an option in children with significant neurologic deficits and proven arterial occlusion, especially when the therapeutic window for intravenous thrombolysis has been exceeded.


Subject(s)
Brain Ischemia/surgery , Stroke/surgery , Thrombectomy , Brain/diagnostic imaging , Brain/pathology , Brain/surgery , Brain Ischemia/etiology , Brain Ischemia/pathology , Carotid Artery Diseases/complications , Carotid Artery Diseases/pathology , Carotid Artery Diseases/surgery , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/pathology , Carotid Artery, Internal/surgery , Cerebral Angiography , Child , Diffusion Magnetic Resonance Imaging , Female , Follow-Up Studies , Functional Laterality , Humans , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/surgery , Stroke/etiology , Stroke/pathology , Thrombectomy/instrumentation , Tomography Scanners, X-Ray Computed , Treatment Outcome
13.
Neurology ; 81(17): 1500-6, 2013 Oct 22.
Article in English | MEDLINE | ID: mdl-24068784

ABSTRACT

OBJECTIVE: To report the clinical features of 20 newly diagnosed patients with GABAB receptor (GABABR) antibodies and determine the frequency of associated tumors and concurrent neuronal autoantibodies. METHODS: Clinical data were retrospectively obtained and evaluated. Serum and CSF samples were examined for additional antibodies using methods previously reported. RESULTS: Seventeen patients presented with seizures, memory loss, and confusion, compatible with limbic encephalitis (LE), one patient presented with ataxia, one patient presented with status epilepticus, and one patient presented with opsoclonus-myoclonus syndrome (OMS). Nineteen (95%) patients eventually developed LE during the course of the disease. Small-cell lung cancer (SCLC) was identified in 10 (50%) patients, all with LE. Treatment and outcome was available from 19 patients: 15 showed complete (n = 7) or partial (n = 8) neurologic improvement after steroids, IV immunoglobulins, or plasma exchange and oncologic treatment when indicated; 1 patient died of tumor progression shortly after the first cycle of immunotherapy, and 3 were not treated. Five patients with SCLC had additional onconeuronal antibodies (Ri, amphiphysin, or SOX1), and 2 without tumor had GAD65 and NMDAR antibodies, respectively. GABABR antibodies were not detected in serum of 116 patients with SCLC without neurologic symptoms. CONCLUSION: Our study confirms GABABR as an autoantigen of paraneoplastic and nonparaneoplastic LE and expands the phenotype of GABABR antibodies to ataxia, OMS, and status epilepticus. The long-term prognosis is dictated by the presence of a tumor. Recognition of syndromes associated with GABABR antibodies is important because they usually respond to treatment.


Subject(s)
Autoantibodies/biosynthesis , Limbic Encephalitis/immunology , Lung Neoplasms/immunology , Receptors, GABA-B/immunology , Small Cell Lung Carcinoma/immunology , Adolescent , Adult , Aged , Ataxia/blood , Ataxia/cerebrospinal fluid , Ataxia/immunology , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Female , Follow-Up Studies , Humans , Limbic Encephalitis/blood , Limbic Encephalitis/cerebrospinal fluid , Lung Neoplasms/blood , Lung Neoplasms/cerebrospinal fluid , Male , Middle Aged , Opsoclonus-Myoclonus Syndrome/blood , Opsoclonus-Myoclonus Syndrome/cerebrospinal fluid , Opsoclonus-Myoclonus Syndrome/immunology , Prognosis , Retrospective Studies , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/cerebrospinal fluid , Status Epilepticus/blood , Status Epilepticus/cerebrospinal fluid , Status Epilepticus/immunology , Young Adult
14.
Rev Neurol ; 54(10): 593-600, 2012 May 16.
Article in Spanish | MEDLINE | ID: mdl-22573506

ABSTRACT

INTRODUCTION: Descompressive craniectomy (DC) for treatment of malignant infarction of the middle cerebral artery (MIMCA) reduces mortality and increases the probability of favourable outcome. AIM: To present the experience in daily practice after implantation of a clinical protocol of DC. PATIENTS AND METHODS: Prospective register of patients with MIMCA treated with DC. Age, stroke severity -National Institute of Health Stroke Scale (NIHSS) score-, basal characteristics, delay until DC, mortality, modified Rankin Scale (mRS) score at three and twelve months and questionnaire of satisfaction are recorded. RESULTS: From February 2008 to December 2010, 15 patients were treated. Mean age: 60 years (range: 35-69); basal NIHSS, median (p25/p75): 17 (15.5/21), NIHSS before craniectomy: 20 (18/23.5). DC was performed within 48 hours in 8 patients (53.3%). 5 subjects (33.3%) died during in-hospital stay. Mortality was 25% among those treated within 48 hours and 42.9% among those treated later and 37.5% among patients <= 60 years vs 28.6% in older patients. All survivors scored <= 4 in the mRS at three months and expressed satisfaction with surgery despite sequelae. Rate of favourable outcome (mRS <= 3) was higher among patients under 60 (63%) and among those treated before 48 h (50%). CONCLUSION: DC is safe in clinical practice and reduces mortality after MIMCA, especially if it is performed within 48 hours from stroke onset. Benefit appears to be greater in younger patients, but older people may benefit also. The decision to perform DC should be made on an individual basis.


Subject(s)
Decompressive Craniectomy , Infarction, Middle Cerebral Artery/surgery , Adult , Aged , Clinical Protocols , Female , Humans , Male , Middle Aged , Prospective Studies
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