Enfermedad ateroembólica. Presentación de un caso de afectación multisistémica y revisión de la literatura

The atheroembolic disease is an entity characterized by obstruction of multiple small arteries by cholesterol crystals. The incidence rises steeply with advancing age and following an invasive procedure involving arteries in patients with atherosclerosis. Actually it has a growing interest due to the increased frequency and to the lack of appropriate therapy. In this paper we report a clinical case of multiple system disease secondary to anticoagulant therapy in a 69 years old patient. We review the pathogenesis, clinical features, laboratory dates and pathology of the diseas

Prevalence and Predictors of Cerebral Microangiopathy Determined by Pulsatility Index in an Asymptomatic Population From the ILERVAS Project

Background: Little is known about the prevalence of cerebral microangiopathy (CM), which is related to cognitive impairment, in an asymptomatic population. Pulsatility index (PI) is an easily measurable parameter of cerebral vascular resistance in transcranial duplex of the middle cerebral artery (MCA) study. We aimed to determine the prevalence of CM measured by PI of MCA in low to moderate vascular risk subjects. Methods: We included 3,721 subjects between 45 and 70 years without previous history of vascular disease or diabetes mellitus and with at least one other vascular risk factor from the cross-sectional study ILERVAS (Lleida, Spain). Patients underwent transcranial duplex to determine MCA-PI. Possible CM was defined by MCA-PI >1.1. Carotid and femoral arteries ultrasound registration was done to determine the presence, the number, and the area of atheromatous plaques. Body mass index (BMI), pulse pressure (PP) and laboratory data were also recorded. Results: 439 (11.8%) subjects were excluded due to the low quality of transcranial duplex images. Median age was 57 [IQR 52, 62] years. Possible CM was found in 424 (12.9%) subjects. CM patients had higher prevalence of plaques than non-CM (77.4 vs. 66.4%, p < 0.001). PI showed a positive linear correlation with the number of territories with plaques (r = 0.130, p < 0.001), and the total plaque area (r = 0.082, p < 0.001). The predictors of possible CM were the age, male gender, and PP. Conclusions: In low-to-moderate vascular risk asymptomatic population, the proportion of abnormal brain microvascular bed determined by MCA-PI is not negligible. The planned 10-year follow-up will describe the clinical relevance of these findings.This work was supported by grants from the Diputacio de Lleida, Instituto de Salud Carlos III (RETIC RD16/0009/0011) and Ministerio de Ciencia, Inovación y Universidades (IJC2018-037792-I). FP was supported by the Catalan Autonomous Government’s Agència de Gestió d’Ajuts Universitaris i de Recerca (2017 suport a les activitats dels grups de recerca 1628). RP was supported by the Spanish Ministry of Science, Innovation, and Universities (grant RTI2018-099200-B-I00), and the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR696). This study was co-financed by FEDER funds from the European Union (A way to build Europe). IRBLleida is a CERCA Programme/Generalitat of Catalonia

Inflammatory Response of Ischemic Tolerance in Circulating Plasma : Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)

Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT. A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days. Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0-4.0]; group 2: 2.0 [0.0-3.0]; group 3: 1.0 [0-2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7-18.3]; group 2: 0.8 [0.3-8.9]; group 3: 0.6 [0.1-5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel. Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA

Pre-neoplastic alterations define CLL DNA methylome and persist through disease progression and therapy

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in preneoplastic monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significant differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and posttherapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state and a distinct expression profile together with MBL cells compared with normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically driven growth dynamics, and, together with its persistent presence, suggests a central role in disease onset. SigNifiCANCe: DNA methylation data from a large cohort of patients with MBL and CLL show that epigenetic transformation emerges early and persists throughout disease stages with limited subsequent changes. Our results indicate an early role for this aberrant landscape in the normal-to-preneoplastic transition that may reflect a pan-cancer mechanism

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself

Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1, 810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.This project was funded by Asociacion Investigacion Solidaria SADAR, Caja Navarra (Navarra, Spain) and the Spanish Agency for International Development Cooperation (AECID) (Project 08-CAP2-0609)

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. Conclusion: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately

Effectiveness of thrombectomy in stroke according to baseline prognostic factors: inverse probability of treatment weighting analysis of a population-based registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups’ criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors