Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention. DEVELOPMENT: We reviewed the most recent studies related to lifestyle and stroke risk, including randomised clinical trials, population studies, and meta-analyses. The risk of stroke associated with such lifestyle habits as smoking, alcohol consumption, stress, diet, obesity, and sedentary lifestyles was analysed, and the potential benefits for stroke prevention of modifying these habits were reviewed. We also reviewed stroke risk associated with exposure to air pollution. Based on the results obtained, we drafted recommendations addressing each of the lifestyle habits analysed. CONCLUSIONS: Lifestyle modification constitutes a cornerstone in the primary and secondary prevention of stroke. Abstinence or cessation of smoking, cessation of excessive alcohol consumption, avoidance of exposure to chronic stress, avoidance of overweight or obesity, a Mediterranean diet supplemented with olive oil and nuts, and regular exercise are essential measures in reducing the risk of stroke. We also recommend implementing policies to reduce air pollution.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Guidelines for the treatment of acute ischaemic stroke.

INTRODUCTION: Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. DEVELOPMENT: Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. CONCLUSION: Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated.

[Endovascular treatment in acute ischaemic stroke. A stroke care plan for the region of Madrid]. / Tratamiento endovascular en el ictus isquémico agudo. Plan de Atención al Ictus en la Comunidad de Madrid.

INTRODUCTION: Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures. DEVELOPMENT: After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke. The protocol includes methodology recommendations for diagnosing and selecting patients, performing revascularisation procedures, and for subsequent patient management. Its objective is to increase the likelihood of efficacy and treatment benefit and minimise risk of complications and ineffective recanalisation. Based on an analysis of healthcare needs and available resources, a cooperative inter-hospital care system has been developed. This helps to ensure availability of endovascular therapies to all patients, a fast response time, and a good cost-to-efficacy ratio. It includes also a prospective register which serves to monitor procedures in order to identify any opportunities for improvement. CONCLUSIONS: Implementation of endovascular techniques for treating acute ischaemic stroke requires the elaboration of evidence-based clinical protocols and the establishment of appropriate cooperative healthcare networks guaranteeing both the availability and the quality of these actions. Such procedures must be monitored in order to improve methodology.

Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style.

OBJECTIVE: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). METHODS: We reviewed available evidence on risk factors and means of modifying them to prevent ischaemic stroke and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. RESULTS: This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. CONCLUSIONS: Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing ischemic stroke.

Utility of the assessment of echogenicity in the identification of symptomatic carotid artery atheroma plaques in ischemic stroke patients.

BACKGROUND AND PURPOSE: Echogenicity of atheroma carotid plaques is related to a higher risk of stroke. Clinical and subjective ultrasound criteria are used to identify symptomatic plaques, but the standardized grayscale median (GSM) value may be an objective tool for this diagnosis. Our aim was to analyze the utility of assessing the echogenicity of atheroma carotid plaques in the identification of symptomatic plaques. METHODS: Observational prospective study with inclusion of acute noncardioembolic anterior cerebral circulation ischemic stroke patients. Only patients with bilateral atheroma plaques were included. Echogenicity of plaques was measured by a digital and standardized grayscale system in carotid ultrasound B-mode (longitudinal projection) conducted within the first week after admission. RESULTS: Sixty-six patients were included and 132 plaques were examined. Symptomatic atheroma plaques were less echogenic than asymptomatic ones (GSM 20.0 vs. 29.0; p = 0.002). A ROC curve analysis showed the predictive value of GSM with an AUC of 0.707 (95% CI 0.592-0.823; p = 0.002) and pointed to a value of 24.4 as the optimal cut-off level to identify a plaque as symptomatic (74% sensitivity; 67% specificity). This GSM cut-off point remained significantly associated with a high probability of symptomatic plaque even after the inclusion of the degree of carotid stenosis (either >70% or >50%) in the multivariate logistic regression models. CONCLUSIONS: The assessment of echogenicity of atheroma carotid plaques by the GSM value combined with clinical characteristics and stenosis degree may be useful in the identification of symptomatic plaques.

[Molecular remission of chronic myeloid leukaemia in a patient with hepatitis and a second kidney transplant]. / Remisión molecular de una leucemia mieloide crónica en un paciente con segundo trasplante renal y hepatitis.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by clonal expansion of cells in the myeloid line, expressing the BCR-ABL fusion protein responsible for the oncogenic effect of CML. The current frontline therapy in CML is the BCR-ABL tyrosine kinase inhibitor, Imatinib. Although this drug has been shown to improve survival in CML patients, its role in the context of a transplant setting has not been widely described in the literature. We report on the long term molecular remission of CML in a 55 year old man with a second renal transplant who is hepatitis C virus positive, and has associated cardiovascular and immunological risk factors.

Stroke due to septic embolism resulting from Aspergillus aortitis in an immunocompetent patient.

INTRODUCTION: Cerebral infarction secondary to Aspergillus arteritis or septic embolism is an exceptional finding. We present a case of multiple systemic embolism and cerebral infarction resulting from Aspergillus aortitis in an immunocompetent patient. PATIENT: A 65-year-old male with hypertension, hyperglycaemia and myocardial infarction with aorto-coronary by-pass surgery three years before admission, that suffered cerebral infarction in middle right cerebral artery territory and right cubital artery embolism. One month later he presented abrupt increase of his left hemiparesia and left central facial palsy associated with fever of unknown origin. Laboratory test, cranial CT and echocardiogram were performed. He died ten days later. RESULTS: Hemogram: leucocytes 34.700/microL (85% N, 4.8%L). Cranial CT: cerebral infarction in middle right cerebral artery territory. Transthoracic and transesophageal echocardiogram: moderate left ventricular hypertrophy and slight inferior hypokinesis. Arteriography: complete thrombosis of the left internal carotid. Necropsy: parietal aortic aspergillosis with generalized septic embolisms (brain, kidney, liver, fingers), cerebral infarction in middle right cerebral artery territory and thrombosis of the left carotid siphon with Aspergillus arteritis. CONCLUSIONS: Aspergillosis is an exceptional cause of cerebral infarction, especially in immunocompetent patients, and their diagnosis is complicated, being usually found at necropsy.

Comparison of the MagNA pure LC automated system and the RiboPure-Blood RNA manual method for RNA extraction from multiple myeloma bone marrow samples conserved in an RNA stabilizer.

A total of 62 frozen bone marrow specimens conserved in RNA later (Ambion) were processed using two different extraction methods, the MagNA Pure LC system (MAG; Roche) and the manual RiboPure-Blood RNA method (RIBO; Ambion); Beta glucoronidase RNA (GUS) was amplified by LightCycler PCR to evaluate the quality of both extraction procedures. Less than 1000 GUS copies/ml was detected in 26 of 62 specimens (41.94%) processed by MAG and in five of 62 specimens (8.06%) processed by RIBO. Moreover, RNA recovery from the 62 specimens by MAG is, on average, 2.91 cycle threshold-fold higher than RIBO (P = 0.0008). Furthermore, we compared the extraction times and reagent costs of both methods. In conclusion, RNA extraction using MAG is faster to process 32 samples and less expensive than RIBO but it is not sensitive enough to be employed for research purpose in our laboratory.

[Benign intracranial hypertension. History, clinical features and treatment in a series of 41 patients]. / Hipertensión intracraneal benigna. Antecedentes, clínica y tratamiento en una serie de 41 pacientes.

INTRODUCTION: Benign intracranial hypertension (BIH) is a syndrome characterized by the abnormal elevation of the intracranial pressure with a normal composition of the cerebrospinal fluid (CSF) and in absence of ventriculomegaly or some intracranial expansive lesion. AIM: The present work seeks, by means of the analysis of diagnosed BIH patients to evaluate its epidemic, clinical and therapeutic features. PATIENTS AND METHODS: 87 histories from intracranial hypertension diagnosed patients with normal cerebral CT were reviewed, between 1999 and 2002. 41 BIH patients were selected. RESULTS: The reached results allow us to draw the following profile, a woman (> 70%) of between 21 and 30 years (29%), smoker, obese (59%) with an recent increase of weight (37%) that consults after spending more than three months with headache (89%), alterations of the visual acuity (> 50%) and nauseas with some vomiting (> 40%). In the exploration, it presents with bilateral papilledema (100%), a CSF pressure bigger than 20 cmH2O (40,78 15,55 cmH2O) with normal composition, without alterations in the neuroradiological study results. CONCLUSION: The treatment with acetazolamide was favourable (51,2%), being definitive (70%) the lumbar peritoneal shunt when it is specified (30,7%), being improved these figures in those patients with a smaller pressure of the CSF in the moment of the diagnosis (p<0,035).