Association between spontaneous internal carotid artery dissection and perivascular adipose tissue attenuation on computed tomography angiography.

BACKGROUND: Spontaneous cervical artery dissection (sCAD) is a leading cause of ischemic stroke in young patients. Studies using high-resolution magnetic resonance imaging and positron emission tomography have suggested vessel wall inflammation to be a pathogenic factor in sCAD. Computed tomography (CT) attenuation of perivascular adipose tissue (PVAT) is an established non-invasive imaging biomarker of inflammation in coronary arteries, with higher attenuation values reflecting a greater degree of vascular inflammation. OBJECTIVES: We evaluate the CT attenuation of PVAT surrounding the internal carotid artery (PVATcarotid) with and without spontaneous dissection. METHODS: Single-center prospective observational study of 56 consecutive patients with CT-verified spontaneous dissection of the internal carotid artery (ICA). Of these patients, six underwent follow-up computed tomography angiography (CTA). Twenty-two patients who underwent CTA for acute neurological symptoms but did not have dissection formed the control group. Using semi-automated research software, PVATcarotid was measured as the mean Hounsfield unit (HU) attenuation of adipose tissue within a defined volume of interest surrounding the ICA. RESULTS: PVATcarotid was significantly higher around dissected ICA compared with non-dissected contralateral ICA in the same patients (-58.7 ± 10.2 vs -68.9 ± 8.1 HU, p < 0.0001) and ICA of patients without dissection (-58.7 ± 10.2 vs -69.3 ± 9.3 HU, p < 0.0001). After a median follow-up of 89 days, there was a significant reduction in PVATcarotid around dissected ICA (-57.5 ± 13.4 to -74.3 ± 10.5 HU, p < 0.05), while no change was observed around non-dissected contralateral ICA (-71.0 ± 4.4 to -74.1 ± 4.1 HU, p = 0.19). ICA dissection was an independent predictor of PVATcarotid following multivariable adjustment for age and the presence of ICA occlusion. CONCLUSION: PVATcarotid is elevated in the presence of sCAD and may decrease following the acute event.

Quality of life in patients with heart failure and improved ejection fraction: one-year changes and prognosis.

AIMS: The criteria for patients with heart failure (HF) and improved ejection fraction (HFimpEF) are a baseline left ventricular ejection fraction (LVEF) ≤40%, a ≥10-point increase from baseline LVEF, and a second LVEF measurement >40%. We aimed to (i) assess patients with HF and reduced LVEF (HFrEF) at baseline and compare quality of life (QoL) changes between those that fulfilled and those that did not fulfil the HFimpEF criteria 1 year later and (ii) assess the prognostic role of QoL in patients with HFimpEF. METHODS: We reviewed data from a prospective registry of real-world outpatients with HF that were assessed for LVEF and QoL at a first visit to the HF clinic and 1 year later. QoL was evaluated with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The primary prognostic endpoint was the composite of all-cause death or HF hospitalization. RESULTS: Baseline and 1-year LVEF and MLWFQ scores were available for 1040 patients with an initial LVEF ≤40% (mean age, 65.2 ± 11.7 years; 75.9% men). The main aetiology was ischaemic heart disease (52.9%), and patients were mostly in New York heart Association Classes II (71.1%) and III (21.6%). At baseline, the mean LVEF was 28.5% ± 7.3, and the mean MLWHFQ score was 30.2 ± 19.5. After 1 year, the mean LVEF increased to 38.0% ± 12.2, and the MLWHFQ scores improved to 17.4 ± 16.0. In 361 patients that fulfilled the HFimpEF criteria (34.7%), significant improvements were observed in both LVEF (from 28.7% ± 6.6 to 50.9% ± 7.6, P < 0.001) and QoL (from 32.9 ± 20.6 to 16.9 ± 16.0, P < 0.001). Patients that did not fulfil the HFimpEF criteria also showed significant improvements in LVEF (from 28.4% ± 7.6 to 31.1% ± 7.9, P < 0.001) and QoL (from 28.7 ± 18.8 to 17.6 ± 15.9, P < 0.001). However, the QoL improvement was significantly higher in the HFimpEF group (-16.0 ± 23.8 vs. -11.1 ± 20.3, P = 0.001), despite the worse mean baseline MLWHFQ score, compared with the non-HFimpEF group (P = 0.001). The 1-year QoL was similar between groups (P = 0.50). The 1-year MLWHFQ score was independently associated with outcomes; the hazard ratio for the composite endpoint was 1.02 (95% CI: 1.01-1.03, P = 0.006). In contrast, the QoL improvement (with a cut-off ≥5 points) was not independently associated with the composite outcome. CONCLUSIONS: Patients with HFrEF showed improved QoL after 1 year, regardless of whether they met the HFimpEF criteria. The similar 1-year QoL perception between groups suggested that factors other than LVEF influenced QoL perception. The 1-year QoL was superior to the QoL change from baseline for predicting prognosis in patients with HFimpEF.

Cervical Artery Dissection in Postpartum Women after Cesarean and Vaginal Delivery.

BACKGROUND AND AIMS: Cervical artery dissection (CAD) is an infrequent but potentially disabling and fatal disease, accounting for up to 25 % of strokes in young adults. Pregnancy-related hormonal changes and increased hemodynamic stress on artery walls during vaginal delivery have been associated to CAD. We aim to describe a series of women presenting CAD during postpartum (PP) after cesarean and vaginal delivery. METHODS: CAD women admitted to one hospital in Santiago, Chile, between July 2018 and October 2020 were included in a prospective cohort. Demographic, clinical and imaging data were registered for the PP group. RESULTS: Sixty-seven women were diagnosed with CAD, from which 10 were PP. Seven women had cesarean section and 3 had vaginal delivery. They presented CAD related symptoms after a median of 10.5 (IQR 5-15) days from delivery. All of them had headache as initial symptom, 9 presented cervical pain and 8 had a family history of stroke. Four patients presented preeclampsia during pregnancy. Acute treatment consisted mostly in antiplatelet agents and analgesics. None of these patients had a CAD related stroke. Demographic, clinical and imaging characteristics of these women with CAD during PP are described. CONCLUSIONS: This case series underpins the importance of clinical suspicion of CAD after delivery, highlighting the fact that CAD is not limited to women with vaginal delivery, thus alternative causes beyond acute hemodynamic stress could be involved. Further research is required to determine genetic components, along with deeper knowledge of modulating factors related to CAD in this setting.

Lung ultrasound in outpatients with heart failure: the wet-to-dry HF study.

AIMS: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. METHODS AND RESULTS: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B-lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right-sided, left-sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all-cause death or HF-related hospitalization. Two hundred and thirty-three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B-line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B-lines (20.6 ± 11), followed by left-sided (19.7 ± 11.6) and right-sided (13.5 ± 9.8). B-lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6-40)]. B-lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01-1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B-line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01-1.07), P = 0.014], with a 4% increase risk per B-line added. B-lines correlated significantly with CA125 (R = 0.30, P = 0.001). CONCLUSIONS: Lung ultrasound supports the diagnostic work-up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short-term events.

Real-world experience of ocrelizumab in multiple sclerosis patients in Latin America.

BACKGROUND: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles. OBJECTIVE: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America. METHODS: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging. RESULTS: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days. CONCLUSIONS: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.

Thirst distress in outpatients with heart failure in a Mediterranean zone of Spain.

AIMS: This study aimed to evaluate psychometric properties of the Spanish version of the Thirst Distress Scale for patients with Heart Failure (TDS-HF) and to describe thirst distress-associated factors in outpatients at a heart failure (HF) clinic in Spain. Thirst is common in patients with HF, but thirst distress has rarely been addressed and may significantly decrease quality of life. METHODS AND RESULTS: A cross-sectional study was performed assessing perceived thirst distress by patients with HF during the preceding 3 days, with the TDS-HF (scores 8 to 40). Univariable and multivariable linear regression analyses were performed to identify variables independently associated with thirst distress. Three-hundred two HF outpatients were included (age 67 ± 12 years, 74% male, HF duration 82 ± 75 months, left ventricular ejection fraction 42 ± 14%). Most patients were on treatment with fluid restriction (99%), sodium restriction (99%), and diuretics (70%). The psychometric evaluation of the Spanish version of the TDS-HF showed satisfactory item-total and inter-item correlations (range from 0.77 to 0.85 and 0.60 to 0.84, respectively), and internal consistency was 0.95 (Cronbach's alpha). The majority perceived mild to moderate thirst distress, and 18% perceived it as high or severe. The mean score obtained was 16.2 ± 9.3 (median 13, Q1-Q3 8-20). Higher serum urea {beta coefficient 1.6 [95% confidence interval (CI) 0.267 to 2.92], P = 0.019} and lower potassium [beta coefficient -3.63 (85% CI -6.32 to -0.93), P = 0.009] remained significantly associated with thirst distress in the multivariable analysis, together with the dose of diuretics [beta coefficient 2.98 (95% CI 1.37 to 4.59), P < 0.001]. Treatment with angiotensin receptor blocker showed an independent protective effect [beta coefficient -3.62 (95% CI -6.89 to -0.345), P = 0.03]. CONCLUSIONS: The psychometric evaluation of the Spanish version of the TDS-HF showed good psychometric properties. One in five patients experienced severe distress by thirst, but the majority had mild to moderate thirst distress. The dose of diuretics and angiotensin receptor blocker treatment influence thirst distress and could be clinically important targets to relieve thirst distress in patients with HF.

Real-world experience of ocrelizumab in multiple sclerosis patients in Latin America / Experiencia en la vida real con el uso de ocrelizumab en pacientes con esclerosis múltiple en Latinoamérica

ABSTRACT Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles. Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America. Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging. Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days. Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.

RESUMEN Introducción: A pesar de la abundante información sobre ocrelizumab proveniente de los ensayos clínicos de fase III, todavía se tiene poca evidencia sobre la efectividad y el perfil de pacientes provenientes de la vida real. Objetivo: Evaluar el perfil clínico y demográfico, la efectividad y la persistencia al tratamiento en pacientes que usaron el ocrelizumab para el tratamiento de esclerosis múltiple (EM) en Latinoamérica. Métodos: Estudio retrospectivo multicéntrico en Argentina, Chile y México. Se analizaron los datos de los pacientes que recibieron ocrelizumab. Se describieron las variables demográficas y clínicas, así como los resultados de efectividad que incluyeron la proporción de pacientes libres de recaídas clínicas, libres de progresión de la discapacidad, libres de nuevas lesiones en la secuencia T2 o T1 con gadolinio durante el seguimiento. Resultados: Se incluyeron 81 pacientes. El fenotipo más frecuente fue EM remitente recurrente (EMRR) en el 64,2% de los pacientes. La edad media fue de 41.3±12 años, y el 51,8% eran mujeres. Un total de 38% tuvo recaídas durante los 12 meses previos al inicio de ocrelizumab, con una tasa anualizada de recaídas media de 1.3±0.6 durante ese período. En el seguimiento a 12 meses, el 75% estuvo libre de recaídas clínicas y el 91%, libre de nuevas lesiones en RM. Tres pacientes interrumpieron el tratamiento durante el seguimiento (3,7%). La persistencia al tratamiento observada durante el primer año de seguimiento fue de 338±24 días. Conclusión: Nuestro estudio está en línea con los datos provenientes de ensayos clínicos aleatorizados previos y estudios recientes del mundo real que describen la efectividad de los perfiles de pacientes y la persistencia al tratamiento con ocrelizumab en pacientes con EM en Latinoamérica.

Incidence, risk factors, prognosis, and health-related quality of life after stroke in a low-resource community in Chile (ÑANDU): a prospective population-based study.

BACKGROUND: Stroke is a leading cause of disability and death worldwide. The best estimates of local, national, and global burden of stroke are derived from prospective population-based studies. We aimed to investigate the incidence, risk factors, long-term prognosis, care, and quality of life after stroke in the Ñuble region of Chile. METHODS: We did a prospective community-based study with use of multiple overlapping sources of hospitalised, ambulatory, and deceased cases. Standardised diagnostic criteria were used to identify and follow up all cases occurring in the resident population of the Ñuble region, Chile (in a low-income rural-urban population including predominantly people of Indigenous-European heritage), for 1 year. Participants were included if they had a clinical diagnosis of stroke confirmed according to the study criteria. All cases were adjudicated by vascular neurologists. Incidence rates of first-ever stroke were calculated from the population of Ñuble according to the 2017 national census. FINDINGS: From April 1, 2015, to March 31, 2016, we ascertained 1103 stroke cases, of which 890 (80·7%) were first-ever incident cases. The mean age of patients with first-ever stroke was 70·3 years (SD 14·1) and 443 (49·8%) were women. A CT scan was obtained in 801 (90%) of 890 patients (mean time from symptom onset to scan of 13·4 h (SD 29·8). The incidence of first-ever stroke age-adjusted to the world population was 121·7 (95% CI 113·7-130·1) per 100 000. The age-adjusted incidence rates, per 100 000 inhabitants, by main pathological subtypes were as follows: ischaemic stroke (101·5 [95% CI 90·9-113·0]); intracerebral haemorrhage (17·9 [13·5-23·4]), and subarachnoid haemorrhage (4·2 [2·1-7·3]). The 30-day case-fatality rate was 24·6% (21·9-27·6). At 6 months after the stroke, 55·9% (432 of 773) of cases had died or were disabled, which increased to 61·0% (456 of 747) at 12 months. Health-related quality of life in survivors was low at 6 months, improving slightly at 12 months after the stroke. INTERPRETATION: The incidence of stroke in this low-resource population was higher than our previous finding in northern Chile and within the mid-range of most population-based stroke studies. This result was due mainly to a higher incidence of ischaemic stroke, probably associated with increasing age and a high prevalence of cardiometabolic risk factors in the population studied. Our findings suggest that more should be done for the prevention and care of stroke in communities like the Ñuble population. FUNDING: The National Agency for Research and Development and the Technology-Health Research Fund, Clínica Alemana de Santiago, Boehringer Ingelheim, Bristol Meyers Squibb, The Herminda Martin Clinical Hospital of Chillán, Universidad Mayor, and Universidad de Concepción.

Cryptococcus bacillisporus (VGIII) Meningoencephalitis Acquired in Santa Cruz, Bolivia.

We describe a case of chronic meningoencephalitis with hydrocephalus caused by Cryptococcus bacillisporus (VGIII) in an immunocompetent patient from Santa Cruz, Bolivia. This first report of a member of the Cryptococcus gattii species complex from Bolivia suggests that C. bacillisporus (VGIII) is present in this tropical region of the country and complements our epidemiological and clinical knowledge of this group of emerging fungal pathogens in South America.

Prognostic value of lung ultrasound in chronic stable ambulatory heart failure patients.

INTRODUCTION AND OBJECTIVES: The role of lung ultrasound (LUS) in acute heart failure (HF) has been widely studied, but little is known about its usefulness in chronic HF. This study assessed the prognostic value of LUS in a cohort of chronic HF stable ambulatory patients. METHODS: We included consecutive outpatients who attended a scheduled follow-up visit in a HF clinic. LUS was performed in situ. The operators were blinded to clinical data and examined 8 thoracic areas. The sum of B-lines across all lung zones and the quartiles of this addition were used for the analyses. Linear regression and Cox regression analyses were performed. The main clinical outcomes were a composite of all-cause death or hospitalization for HF and mortality from any cause. RESULTS: A total of 577 individuals were included (72% men; 69± 12 years). The mean number of B-lines was 5±6. During a mean follow-up of 31±7 months, 157 patients experienced the main clinical outcome and 111 died. Having ≥ 8 B-lines (Q4) doubled the risk of experiencing the composite primary event (P <.001) and increased the risk of death from any cause by 2.6-fold (P <.001). On multivariate analysis, the total sum of B-lines remained independent predictive factor of the composite endpoint (HR, 1.04; 95%CI, 1.02-1.06; P=.002) and of all-cause death (HR, 1.04; 95%CI, 1.02-1.07; P=.001), independently of whether or not N-terminal pro-B-type natriuretic peptide (NT-proBNP) was included in the model (P=.01 and P=.008, respectively), with a 3% to 4% increased risk for each 1-line addition. CONCLUSIONS: LUS identified patients with stable chronic HF at high risk of death or HF hospitalization.

Thirst and factors associated with frequent thirst in patients with heart failure in Spain.

BACKGROUND: Thirst is a troublesome symptom in patients with Heart Failure (HF) and one that might be perceived differently in different countries depending on climate, food and cultural habits. The aims of the study were to describe thirst frequency, duration and intensity and to identify factors associated with frequent thirst in outpatients with HF in a Mediterranean country. METHODS: Data was collected in a cross-sectional study involving 302 patients diagnosed with HF (age 67±12 years, 74% male, LVEF 43%±14) in Spain on thirst frequency and duration, and thirst intensity by patient self-report (VAS, 0-100 mm). Clinical variables were collected from the medical files. Regression analysis was used to identify factors independently associated with frequent thirst. RESULTS: Of all the patients, 143 (47%) were frequently thirsty, and their median (25th and 75th percentiles) thirst intensity was higher (VAS 50 mm [20-67] vs 7 [0-20], p<.001). Their thirst lasted longer compared to those who never/sometimes were thirsty (p<.001). Less treatment with angiotensin receptor blockers (Odds Ratio [OR] 2.72; 95% Confidence Interval [CI] 1.33-5.58), diuretics >40 mg/day (OR 1.92; 95% CI 1.02-3.64), depression (OR 2.99; CI 1.17-7.62), male gender (OR 1.98; CI 1.08-3.64) and worse New York Heart Association functional class (OR 1.92; 95% CI 1.05-3.52) were independently associated with frequent thirst. CONCLUSIONS: About half of patients with HF and fluid restriction experienced frequent thirst in a Mediterranean area of Spain, and their thirst duration and intensity were significantly increased. Frequent thirst was associated with demographic, clinical and therapeutic variables. The results may help to identify patients with a higher risk of frequent thirst and might suggest therapeutic changes in order to diminish this troublesome symptom.

Reconsidering systematic factors during the Covid-19 pandemic - The rising importance of ESG.

We investigate the importance of Environmental, Social and Governance (ESG) ratings in explaining different industry returns during the Covid-19 window. We build our ESG factor as the spread in returns between firms in the top ESG quartile and those in the bottom ESG quartile. The ESG factor shows to significantly explain industry returns in addition to the Fama-French factors. We also analyze the individual Environmental, Social, and Governance components of ESG. Environmental and Social dimensions are the main drivers of the ESG impact on different industries.

Transcranial Doppler as a Predictor of Ischemic Events in Vertebral Artery Dissection.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) helps identify patients with carotid dissections at risk of ischemic events (IEs). There is paucity of data identifying independent predictors of IE in vertebral arterial dissection (VAD). We sought to investigate the clinical and ultrasound predictors of IE. METHODS: Patients with VAD admitted between June 2017 and February 2020 were evaluated clinically and with TCD; sonographic curves, microembolic signals (MES), and the breath-holding index (BHI) test were applied. Covariates found on univariate screen (P < .25) were included in a multivariable linear regression to identify independent predictors of IEs. RESULTS: Of 88 patients with 100 VAD, 75 (85.2%) were females with a mean age 37.9 ± 7.5 years. All patients received antiplatelet treatment. TCD monitoring lasted an average of 21 ± 2.1 minutes. TCD was abnormal in 23 cases (26.1%); 21 patients had abnormal sonographic curves in the vertebral/basilar arteries, while in 4 cases, MES were present and in 5 (4.5%), BHI was abnormal. None of the patients with a normal TCD had an IE. Six strokes occurred during follow up. On univariate analysis, male sex, diabetes, dyslipidemia, a previous myocardial infarct, migraine, time of consultation to the ER, bilateral VAD, MES, BHI abnormalities, post stenotic flow in the basilar artery (PFB), and basilar/vertebral velocities were significantly associated with the risk of IEs. In the multivariate analysis, only the presence of PFB was a significant predictor of IE (OR: 68.6, 95% CI 5-937, <.001). CONCLUSIONS: TCD in VAD predicts patients at high risk of IE.

Inclusion of the Symbol Digit Modalities Test in a revised assessment of 'no evidence of disease activity-4 (NEDA-4)' in Latin-American patients with multiple sclerosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), no evidence of disease activity-3 (NEDA-3) is defined as the absence of: (1) relapses; (2) disability progression; (3) MRI activity (new/enlarged T2 lesions and/or gadolinium-enhanced T1 lesions). NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized percentage brain volume change (a-PBVC) >-0.4%. In individual patients, brain volume assessment is confounded with normal aging, methodological limitations and fluid-shift related fluctuations in brain volume. Cognitive impairment has been proposed as another component that should be integrated into therapeutic algorithms for RRMS. We aim to determine the proportion of patients failing to meet NEDA-4 criteria and to appraise whether the Symbol Digit Modalities Test (SDMT) is capable of replacing a-PBVC as one of the components of NEDA-4. We hypothesize that NEDA-4 has the potential to capture the impact of DMT therapies in RRMS. METHODS: Forty-five patients were prospectively followed 1 and 2 years after their baseline assessment at the University of Chile Hospital. SIENA software was used to assess a-PBVC. RESULTS: At baseline, the patients had a mean age of 33.0 years (range 18-57), disease duration of 1.9 years (0.4-4), Expanded Disability Status Scale score of 1.3 (0-4), and 67% were female. The majority had RRMS (91% while 9% had clinically isolated syndrome (CIS)). Seventy-three percent were on the so-called first line DMTs such as interferons (53%), glatiramer acetate (13%), teriflunomide (9%), and 18% were on fingolimod. There was a serial decline in the proportion of NEDA: after 1 and 2 years of follow-up 60% and 47% met NEDA-3 status, and 38% and 27% met NEDA-4, respectively. At the last follow-up 21% remained on interferons, 47% were now on fingolimod, 4% on alemtuzumab and 2% on natalizumab. At year 1 and year 2, with the replacement of a-PBVC by SDMT, 53% and 40% of patients achieved a putative NEDA-4 status, respectively. CONCLUSION: Brain volumetric MRI has yet to be translated into clinical practice and SDMT may qualify as the fourth component of NEDA-4 definition. NEDA-4 has the potential to capture the impact of DMT therapies in RRMS earlier in the disease course of RRMS.

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice.

Background: In relapsing-remitting multiple sclerosis, no evidence of disease activity-3 (NEDA-3) is defined as no relapses, no disability progression and no MRI activity. NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized brain volume loss (a-BVL) of ≤0.4%. Prospective real-world studies presenting data on NEDA-4 are scarce. Objective: To determine the proportion of patients failing to meet one or more NEDA-4 criteria and the contribution of each component to this failure. Methods: Forty-eight patients were followed for 12 months. Structural image evaluation, using normalization, of atrophy was used to assess a-BVL. Results: The patients had a mean age of 33.0 years (range 18-57), disease duration of 1.7 years (0.4-4) and Expanded Disability Status Scale score of 1.3 (0-4); 71% were women. All patients were on disease-modifying therapies. During follow-up, 21% of the patients had at least one relapse, 21% had disability progression, 8% had new T2 lesions, and 10% had gadolinium-enhanced lesions. Fifty-eight percent (28/48) achieved NEDA-3 status. a-BVL of >0.4% was observed in 52% (25/48). Only 29% (14/48) achieved NEDA-4 status. Conclusion: a-BVL is a good marker to detect subclinical disease activity. a-BVL is parameter to continue investigating for guiding clinical practice in relapsing-remitting multiple sclerosis.

Comorbidities, Fragility, and Quality of Life in Heart Failure Patients With Midrange Ejection Fraction.

OBJECTIVE: To assess the effects of comorbidities, fragility, and quality of life (QOL) on long-term prognosis in ambulatory patients with heart failure (HF) with midrange left ventricular ejection fraction (HFmrEF), an unexplored area. PATIENTS AND METHODS: Consecutive patients prospectively evaluated at an HF clinic between August 1, 2001, and December 31, 2015, were retrospectively analyzed on the basis of left ventricular ejection fraction category. We compared patients with HFmrEF (n=185) to those with reduced (HFrEF; n=1058) and preserved (HFpEF; n=162) ejection fraction. Fragility was defined as 1 or more abnormal evaluations on 4 standardized geriatric scales (Barthel Index, Older Americans Resources and Services scale, Pfeiffer Test, and abbreviated-Geriatric Depression Scale). The QOL was assessed with the Minnesota Living with Heart Failure Questionnaire. A comorbidity score (0-7) was constructed. All-cause death, HF-related hospitalization, and the composite end point of both were assessed. RESULTS: Comorbidities and QOL scores were similar in HFmrEF (2.41±1.5 and 30.1±18.3, respectively) and HFrEF (2.30±1.4 and 30.8±18.5, respectively) and were higher in HFpEF (3.02±1.5, P<.001, and 36.5±20.7, P=.003, respectively). No statistically significant differences in fragility between HFmrEF (48.6%) and HFrEF (41.9%) (P=.09) nor HFpEF (54.3%) (P=.29) were found. In univariate analysis, the association of comorbidities, QOL, and fragility with the 3 end points was higher for HFmrEF than for HFrEF and HFpEF. In multivariate analysis, comorbidities were independently associated with the 3 end points (P≤.001), and fragility was independently associated with all-cause death and the composite end point (P<.001) in HFmrEF. CONCLUSION: Comorbidities and fragility are independent predictors of outcomes in ambulatory patients with HFmrHF and should be considered in the routine clinical assessment of HFmrEF.

Diffusion-weighted imaging determinants for acute ischemic stroke diagnosis in the emergency room.

PURPOSE: The aim of this study was to investigate the clinical-radiological determinants of diffusion-weighted image (DWI) abnormalities in patients with suspected acute ischemic stroke (AIS) seen at the emergency room (ER). METHODS: During the study period, 882 consecutive patients were screened at Clínica Alemana de Santiago, Chile; 786 had AIS and 711 (90.4%) were included. RESULTS: DWI demonstrated 87.3% sensitivity and 99.0% specificity, with a positive likelihood ratio of 79 and a negative likelihood ratio of 0.13 for the detection of AIS. In the univariate analysis, a positive DWI in AIS was associated with admission National Institute of Health Stroke Scale (NIHSS) score (OR 1.09, 95% CI 1.04-1.1%), time from symptom onset to DWI (OR 1.03, 95% CI 1.01-1.05), presence of a relevant intracranial artery occlusion (OR 3.18, 95% CI 1.75-5.76), posterior circulation ischemia (OR 0.44, 95% CI 0.28-0.7), brainstem location of the AIS (OR 0.16, 95% CI 0.093-0.27), infratentorial location of AIS (OR 0.44, 95% CI 0.28-0.70), and lacunar (OR 0.27, 95% CI 0.11-0.68) or undetermined stroke etiology (OR 0.12, 95% CI 0.3-0.31). In multivariate analysis, only admission NIHSS score (OR 1.07, 95% CI 1.01-1.13), time from symptom onset to DWI (OR 1.04, 95% CI 1.01-1.13), brainstem location (OR 0.13, 95% CI 0.051-0.37), and lacunar (OR: 0.4, 95% CI 0.21-0.78) or undetermined etiology (OR: 0.4, 95% CI 0.22-0.78) remained independently associated. CONCLUSION: DWI detects AIS accurately; the positivity of these evaluations in the ER is associated only with NIHSS on admission, time to DWI, brainstem location, and AIS etiology.

Transcranial Doppler as a Predictor of Ischemic Events in Carotid Artery Dissection.

BACKGROUND: We aim to evaluate clinical features and transcranial Doppler (TCD) elements, as predictors of the development of ischemic events (IEs) in patients suffering from spontaneous carotid arterial dissection without stroke (CCADW). METHODS: Consecutive patients with CCADW, seen in Clínica Alemana de Santiago between April 2004 and January 2015, were evaluated clinically, and with TCD, microembolic signals (MES) monitoring and breath hold Index (BHI) test were performed. RESULTS: Forty-one patients with 45 CCADW were included. Mean age 41.9 years, 31 male, and 12 (29.1%) patients present with multiple CCADW. At the moment of TCD evaluation, 17 (41.4%) patients were being treated with antiplatelets and the rest under Heparin. TCD monitoring lasted in average 53.3 minutes and demonstrated at the moment of evaluation, MES in four carotid arteries (11.1%) of 3 patients and 13 (28.8%) abnormal BHI in 11 patients. Six IEs occurred in 3 patients, 3 strokes, and 3 transient ischemic attacks. In the univariate analysis correlating IE with clinical and ultrasonographic findings, the degree of carotid stenosis, the presence of multiple CAD, and the presence of MES plus abnormalities of BHI were significantly associated with the risk of an IE. Multivariable analysis showed that only the presence of MES plus abnormal BHI were significant (P < .001). MES and abnormal BHI were present in the 3 patients and in four arterial territories that had IE. CONCLUSIONS: TCD can identify a subgroup of patients with CCADW who are at high risk of IE.

Trombolisis intravenosa en cuadros imitadores de isquemia cerebral: experiencia de un centro / Thrombolysis in stroke mimics: experience in 10 cases

Background: The effectiveness of intravenous thrombolysis (IVT) in cerebral ischemia is time dependent. Stroke mimics (SM) are frequent in emergency rooms. The effort to reduce door to needle time, can lead to administer thrombolytics to SM. Aim: To describe the frequency and prognosis of SM treated with IVT. Material and Methods: Prospective analysis of all patients evaluated in a Chilean private clinic between December 2004 and July 2015 with a suspected acute ischemic stroke (AIS). We calculated the number of SM that were treated with IVT. In these patients, we analyzed the presence of symptomatic cerebral hemorrhage defined as the presence of a neurological deterioration of four points or more on the National Institute of Health Stroke Scale, the presence of extracranial bleeding according to Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries criteria and the patient’s functional status at three months by modified Rankin scale (MRS). Results: We evaluated 1,417 patients with suspected AIS, of which 240 (16.9%) were finally diagnosed as SM. A total of 197 patients were treated with IVT, of these 10 (5%) corresponded to SM. All SM patients treated with thrombolytic drugs were functionally independent at 3 months and showed no bleeding complications. Conclusions: Occasionally SM patients were treated with IVT. This treatment was not associated with bleeding complications and the prognosis of these patients at three months was favorable.