Clot migration in patients treated with tenecteplase versus alteplase before mechanical thrombectomy.

INTRODUCTION: This study aimed to describe and analyze the rate of clot migration of vessel thrombosis to distal segments in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT) with tenecteplase (TNK) and alteplase (ALT) before mechanical thrombectomy (MT). In addition, we aimed to determine the relationship between thrombus migration and functional prognosis. METHODS: This study followed the STROBE reporting guidelines. We performed a retrospective analysis of a series of patients from November 2017 to April 2023 with an AIS with thrombosis on CT imaging, treated with IVT (TNK or ALT, split into two distinct groups) prior to mechanical thrombectomy. RESULTS: Two hundred and fifty-six patients with large vessel occlusion (LVO) were included. Ninety-six had received TNK. One hundred and sixty had received ALT. Of the 96 TNK patients, 25 experienced either complete recanalization (n = 3) or thrombus migration (n = 22). Of the 160 ALT patients, 20 experienced either complete recanalization (n = 6) or thrombus migration (n = 14). The difference being statistically substantial for the thrombus migration rate (OR = 3.61, 95% confidence interval: 1.63; 7.98). Migration to an irretrievable very distal segment occurred in four (4%) patients with TNK and in three patients (2%) with ALT (p > 0.05). Thrombus migration was not significantly associated to a different functional prognosis, measured through Rankin scale after 3 months (OR = 0.44, 95% confidence interval: 0.17; 1.12). CONCLUSION: The use of TNK over ALT as a fibrinolytic agent is associated with a higher thrombus migration rate. The migration of thrombi to distal segments, which are theoretically less accessible for mechanical thrombectomy, did not result in worse clinical outcomes.

Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial.

INTRODUCTION: Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients. METHODS AND ANALYSIS: A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: NCT04019119.

A rare challenge: A patient with progressive fibrodysplasia ossificans and acute ischemic stroke treated with mechanical thrombectomy.

Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification. Here, we briefly describe the case of a 56-year-old male with known FOP and acute ischemic stroke that underwent mechanical thrombectomy with conscious sedation. Treating physicians should be aware of special medical considerations to prevent flare-ups and inflammation that result from any tissue injuries in this disease. Mechanical thrombectomy is a challenging scenario because general anesthesia and injections should be avoided in these patients. The treatment is still preventive and supportive, but this is the first report of the procedure in a patient with FOP.

Ischemia preconditioning induces an adaptive response that defines a circulating metabolomic signature in ischemic stroke patients.

Transient ischemic attacks (TIAs) before an acute ischemic stroke (AIS) could induce ischemic tolerance (IT) phenomena. with an endogenous neuroprotective role (Ischemic preconditioning. IPC). A consecutive prospective cohort of patients with AIS were recruited from 8 different hospitals. Participants were classified by those with non-previous recent TIA vs. previous TIA (within seven days. TIA ≤7d). A total of 541 AIS patients were recruited. 40 (7.4%). of them had previous TIA ≤7d. In line with IPC. patients with TIA ≤7d showed: 1) a significantly less severe stroke at admission by NIHSS score. 2) a better outcome at 7-90 days follow-up and reduced infarct volumes. 3) a specific upregulated metabolomics/lipidomic profile composed of diverse lipid categories. Effectively. IPC activates an additional adaptive response on increasing circulation levels of structural and bioactive lipids to facilitate functional recovery after AIS which may support biochemical machinery for neuronal survival. Furthermore. previous TIA before AIS seems to facilitate the production of anti-inflammatory mediators that contribute to a better immune response. Thus. the IT phenomena contributes to a better adaptation of further ischemia. Our study provides first-time evidence of a metabolomics/lipidomic signature related to the development of stroke tolerance in AIS patients induced by recent TIA.

Reliability Study of Inertial Sensors LIS2DH12 Compared to ActiGraph GT9X: Based on Free Code.

The study's purpose was to assess the reliability of the LIS2DH12 in two different positions, using the commercial sensor Actigraph GT9X as a reference instrument. Five participants completed two gait tests on a treadmill. Firstly, both sensors were worn on the wrist and around the thigh. Each test consisted of a 1 min walk for participants to become accustomed to the treadmill, followed by a 2 min trial at ten pre-set speeds. Data from both sensors were collected in real-time. Intraclass correlation coefficient (ICC) was used to evaluate the equality of characteristics obtained by both sensors: maximum peaks, minimum peaks, and the mean of the complete signal (sequence of acceleration values along the time) by each axis and speed were extracted to evaluate the equality of characteristics obtained with LIS2DH12 compared to Actigraph. Intraclass correlation coefficient (ICC) was extracted, and a standard deviation of the mean was obtained from the data. Our results show that LIS2DH12 measurements present more reliability than Actigraph GT9X, ICC > 0.8 at three axes. This study concludes that LIS2DH12 is as reliable and accurate as Actigraph GT9X Link and, therefore, would be a suitable tool for future kinematic studies.

The Validity of the Energy Expenditure Criteria Based on Open Source Code through two Inertial Sensors.

Through this study, we developed and validated a system for energy expenditure calculation, which only requires low-cost inertial sensors and open source R software. Five healthy subjects ran at ten different speeds while their kinematic variables were recorded on the thigh and wrist. Two ActiGraph wireless inertial sensors and a low-cost Bluetooth-based inertial sensor (Lis2DH12), assembled by SensorID, were used. Ten energy expenditure equations were automatically calculated in a developed open source R software (our own creation). A correlation analysis was used to compare the results of the energy expenditure equations. A high interclass correlation coefficient of estimated energy expenditure on the thigh and wrist was observed with an Actigraph and Sensor ID accelerometer; the corrected Freedson equation showed the highest values, and the Santos-Lozano vector magnitude equation and Sasaki equation demonstrated the lowest one. Energy expenditure was compared between the wrist and thigh and showed low correlation values. Despite the positive results obtained, it was necessary to design specific equations for the estimation of energy expenditure measured with inertial sensors on the thigh. The use of the same formula equation in two different placements did not report a positive interclass correlation coefficient.

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Phosphorylation of Eukaryotic Initiation Factor 4G1 (eIF4G1) at Ser1147 Is Specific for eIF4G1 Bound to eIF4E in Delayed Neuronal Death after Ischemia.

Ischemic strokes are caused by a reduction in cerebral blood flow and both the ischemic period and subsequent reperfusion induce brain injury, with different tissue damage depending on the severity of the ischemic insult, its duration, and the particular areas of the brain affected. In those areas vulnerable to cerebral ischemia, the inhibition of protein translation is an essential process of the cellular response leading to delayed neuronal death. In particular, translation initiation is rate-limiting for protein synthesis and the eukaryotic initiation factor (eIF) 4F complex is indispensable for cap-dependent protein translation. In the eIF4F complex, eIF4G is a scaffolding protein that provides docking sites for the assembly of eIF4A and eIF4E, binding to the cap structure of the mRNA and stabilizing all proteins of the complex. The eIF4F complex constituents, eIF4A, eIF4E, and eIF4G, participate in translation regulation by their phosphorylation at specific sites under cellular stress conditions, modulating the activity of the cap-binding complex and protein translation. This work investigates the phosphorylation of eIF4G1 involved in the eIF4E/eIF4G1 association complex, and their regulation in ischemia-reperfusion (IR) as a stress-inducing condition. IR was induced in an animal model of transient cerebral ischemia and the results were studied in the resistant cortical region and in the vulnerable hippocampal CA1 region. The presented data demonstrate the phosphorylation of eIF4G1 at Ser1147, Ser1185, and Ser1231 in both brain regions and in control and ischemic conditions, being the phosphorylation of eIF4G1 at Ser1147 the only one found in the eIF4E/eIF4G association complex from the cap-containing matrix (m7GTP-Sepharose). In addition, our work reveals the specific modulation of the phosphorylation of eIF4G1 at Ser1147 in the vulnerable region, with increased levels and colocalization with eIF4E in response to IR. These findings contribute to elucidate the molecular mechanism of protein translation regulation that underlies in the balance of cell survival/death during pathophysiological stress, such as cerebral ischemia.

Tools for Evaluating the Content, Efficacy, and Usability of Mobile Health Apps According to the Consensus-Based Standards for the Selection of Health Measurement Instruments: Systematic Review.

BACKGROUND: There are several mobile health (mHealth) apps in mobile app stores. These apps enter the business-to-customer market with limited controls. Both, apps that users use autonomously and those designed to be recommended by practitioners require an end-user validation to minimize the risk of using apps that are ineffective or harmful. Prior studies have reviewed the most relevant aspects in a tool designed for assessing mHealth app quality, and different options have been developed for this purpose. However, the psychometric properties of the mHealth quality measurement tools, that is, the validity and reliability of the tools for their purpose, also need to be studied. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) initiative has developed tools for selecting the most suitable measurement instrument for health outcomes, and one of the main fields of study was their psychometric properties. OBJECTIVE: This study aims to address and psychometrically analyze, following the COSMIN guideline, the quality of the tools that are used to measure the quality of mHealth apps. METHODS: From February 1, 2019, to December 31, 2019, 2 reviewers searched PubMed and Embase databases, identifying mHealth app quality measurement tools and all the validation studies associated with each of them. For inclusion, the studies had to be meant to validate a tool designed to assess mHealth apps. Studies that used these tools for the assessment of mHealth apps but did not include any psychometric validation were excluded. The measurement tools were analyzed according to the 10 psychometric properties described in the COSMIN guideline. The dimensions and items analyzed in each tool were also analyzed. RESULTS: The initial search showed 3372 articles. Only 10 finally met the inclusion criteria and were chosen for analysis in this review, analyzing 8 measurement tools. Of these tools, 4 validated ≥5 psychometric properties defined in the COSMIN guideline. Although some of the tools only measure the usability dimension, other tools provide information such as engagement, esthetics, or functionality. Furthermore, 2 measurement tools, Mobile App Rating Scale and mHealth Apps Usability Questionnaire, have a user version, as well as a professional version. CONCLUSIONS: The Health Information Technology Usability Evaluation Scale and the Measurement Scales for Perceived Usefulness and Perceived Ease of Use were the most validated tools, but they were very focused on usability. The Mobile App Rating Scale showed a moderate number of validated psychometric properties, measures a significant number of quality dimensions, and has been validated in a large number of mHealth apps, and its use is widespread. It is suggested that the continuation of the validation of this tool in other psychometric properties could provide an appropriate option for evaluating the quality of mHealth apps.

Evaluation of Android and Apple Store Depression Applications Based on Mobile Application Rating Scale.

There are a large number of mobile applications that allow the monitoring of health status. The quality of the applications is only evaluated by users and not by standard criteria. This study aimed to examine depression-related applications in major mobile application stores and to analyze them using the rating scale tool Mobile Application Rating Scale (MARS). A search of digital applications for the control of symptoms and behavioral changes in depression was carried out in the two reference mobile operating systems, Apple (App Store) and Android (Play Store), by means of two reviewers with a blind methodology between September and October 2019 in stores from Spain and the United Kingdom. Eighteen applications from the Android Play Store and twelve from the App Store were included in this study. The quality of the applications was evaluated using the MARS scale from 1 (inadequate) to 5 (excellent). The average score of the applications based on the MARS was 3.67 ± 0.53. The sections with the highest scores were "Functionality" (4.51) and "Esthetics" (3.98) and the lowest "Application Subjective quality" (2.86) and "Information" (3.08). Mobile Health applications for the treatment of depression have great potential to influence the health status of users; however, applications come to the digital market without health control.

Behavior Change Techniques and the Effects Associated With Digital Behavior Change Interventions in Sedentary Behavior in the Clinical Population: A Systematic Review.

Background: Sedentary behavior (SB) negatively impact health and is highly prevalent in the population. Digital behavior change interventions (DBCIs) have been developed to modify behaviors such as SB by technologies. However, it is unknown which behavior change techniques (BCTs) are most frequently employed in SB as well as the effect associated with DBCIs in this field. The aim of this systematic review was: (a) to evaluate the BCT most frequently employed in digital health including all technologies available and interventions aimed at increasing physical activity (PA), reducing sedentary time, and improving adherence to exercise in the clinical population, and (b) to review the effect associated with DBCIs in this field. Methods: The database used was Medline, as well as Scopus, Scielo, and Google Scholar. For the search strategy, we considered versions of behavior/behavioral, mHealth/eHealth/telemedicine/serious game/gamification. The terms related to PA and SB were included, the criteria for inclusion were randomized clinical trials (RCTs), adults, intervention based on digital media, and outcome variable lifestyle modification; a last 5 years filter was included. Michie's Taxonomy was used to identify BCTs. The study was registered under the number PROSPERO CRD42019138681. Results: Eighteen RCTs were included in the present systematic review, 5 of them healthy adults, and 13 of them with some illness. Studies included 2298 sedentary individuals who were followed up for 5 weeks-3 years. The most used BCTs were goal setting, problem solving, review outcomes/goals, feedback on behavior and outcomes of behavior, self-monitoring of behavior, social support, information about health consequences, and behavior practice/rehearsal. The effect associated with DBCIs showed improvements, among several related to PA and physiologic self-reported and anthropometric outcomes. Conclusion: The BCTs most used in digital health to change outcomes related to SB were goals and planning, feedback and monitoring, social support, natural consequences, repetition, and substitution. Besides these findings, DBCIs are influenced by several factors like the type of intervention, patients' preferences and values, or the number of BCTs employed. More research is needed to determine with precision which DBCIs or BCTs are the most effective to reduce SB in the clinical population.

Malignant Left Atrial Appendage Morphology: Current Classification vs H-L System.

INTRODUCTION: In previous studies the risk of stroke recurrence has been associated with the left atrial appendage (LAA) morphology (non-chicken wing (NCW)), knowing those with a greater risk as malignant LAA. Recently, a simpler morphological classification has been suggested with two categories: Low-risk (LAA-L) and High-risk (LAA-H); which could be easier to apply and may correlate better with the risk of embolic stroke. METHODS: Retrospective analysis from a registry of patients with recurrent cardioembolic strokes despite appropriate anticoagulant therapy, in which LAA morphology was studied with cardiac CT scan. LAA morphology was classified according to the four current categories and H-L morphology by the same cardiologist. Other variables associated with a high risk of stroke were also assessed, such as CHA2DS2-VASc score and left atrial (LA) size. RESULTS: Twenty-six cases were included in the analysis. We identified 22 (84.6%) chicken wing (CW), 1 (3.8%) windsock and 3 (11.5%) cactus by the current classification system, while 15 (57.7%) were classified as LAA-H and 11 (42.3%) as LAA-L by the new system. Half of the 22 cases with CW morphology were considered LAA-H, whereas all NCW were also classified as LAA-H. LA diameter and area were significantly higher in cases with LAA-H morphology (p=0.03 and 0.014), and also in those CW and LAA-H, compared to those CW with LAA-L (p=0.035). CONCLUSIONS: With this new classification system more than half of the cases of our malignant LAAs were classified as high-risk morphology. This morphology was also associated with an increased LA size.

Efficacy and safety of a soft contact lens to control myopia progression.

CLINICAL RELEVANCE: The control of myopia progression is currently considered an evidence-based therapeutic need. BACKGROUND: To determine the efficacy and safety of the Esencia lens, a new soft contact lens (SCL) designed to slow down myopia progression in paediatric patients. METHODS: This study was a randomised, parallel, double-masked clinical trial. Seventy myopic (-0.50 to -8.75 D) boys and girls, 7-15-years of age, were randomised and allocated to one of two groups: (i) study (n = 36) or (ii) control (n = 34). Study group patients were given the Esencia lens, a progressive multifocal and reverse geometry SCL. Control group patients were given conventional SCLs. Efficacy measurements (change in cycloplegic autorefraction and axial length) were measured at baseline and at the six-month intervals over a 12- month period. Visual performance measurements were corneal power, comfort, quality of vision and contact lens fitting. Safety measures included detection of adverse events. RESULTS: Mean changes in cycloplegic autorefraction after 12-months were -0.28 ± 0.35 D for study and -0.57 ± 0.52 D for control group patients (p = 0.02). A significantly lower increase in axial length was found in the study group (0.13 ± 0.12-mm) compared to control (0.22 ± 0.14-mm) patients (p = 0.03). Compared to control group patients, there was less myopia progression in the study group: 51 and 41 per cent in terms of cycloplegic autorefraction and axial length, respectively. No significant differences between groups for change in corneal power, comfort, vision quality and contact lens fitting were found (p > 0.05). Regarding safety, there were no serious and/or unexpected adverse events during the study. CONCLUSIONS: The Esencia lens seems to be efficacious in slowing down progression of myopia in children compared to traditional SCLs in the short term, with comparable safety features and visual outcomes.

Assessment of the Quality of Mobile Applications (Apps) for Management of Low Back Pain Using the Mobile App Rating Scale (MARS).

Digital health interventions may improve different behaviours. However, the rapid proliferation of technological solutions often does not allow for a correct assessment of the quality of the tools. This study aims to review and assess the quality of the available mobile applications (apps) related to interventions for low back pain. Two reviewers search the official stores of Android (Play Store) and iOS (App Store) for localisation in Spain and the United Kingdom, in September 2019, searching for apps related to interventions for low back pain. Seventeen apps finally are included. The quality of the apps is measured using the Mobile App Rating Scale (MARS). The scores of each section and the final score of the apps are retrieved and the mean and standard deviation obtained. The average quality ranges between 2.83 and 4.57 (mean 3.82) on a scale from 1 (inadequate) to 5 (excellent). The best scores are found in functionality (4.7), followed by aesthetic content (mean 4.1). Information (2.93) and engagement (3.58) are the worst rated items. Apps generally have good overall quality, especially in terms of functionality and aesthetics. Engagement and information should be improved in most of the apps. Moreover, scientific evidence is necessary to support the use of applied health tools.

Use of the Cardiovascular Polypill in Secondary Prevention of Cerebrovascular Disease: A Real-Life Tertiary Hospital Cohort Study of 104 Patients.

BACKGROUND: The use of the cardiovascular polypill, a fixed-dose combination treatment, is conceived to improve adherence. However, randomized controlled trials (RCTs) may overestimate it. Studies focusing on cerebrovascular disease and real-life efficacy compared with conventional treatment are lacking. METHODS: This is a retrospective, hospital-based cohort study of acute ischaemic stroke patients who were prescribed a polypill (aspirin 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) versus conventional treatment (aspirin 100 mg and other blood pressure/lipid-lowering agents) in secondary prevention (2017-2018). Clinical records were reviewed 90 days after discharge for stroke recurrence, vascular risk factor control, and safety. Adherence was assessed using the adapted Morisky-Green scale. RESULTS: A total of 104 patients were included (61% male; mean age 69.7 ± 13.9 years); 54 were treated with the polypill and 50 with conventional treatment. No baseline differences in clinical or demographic variables were detected. No recurrences were registered in the polypill group, compared to 1 recurrence in the conventional treatment group. A significant reduction of systolic blood pressure (SBP) was achieved in the polypill group (12.1 mm Hg) compared to the conventional treatment group (6.8 mm Hg) (p = 0.002). No significant differences were detected regarding the goal of LDL cholesterol ≤70 mg/dL (41 vs. 44%). The adverse events were mild and their frequency was similar in the two groups (9 vs. 2%, ns). Adherence was similarly good in the two groups (93 vs. 88%, ns). Polypill group adherence was similar to that reported in a previous meta-analysis of RCTs (93 vs. 84%, ns). CONCLUSION: In our experience, the cardiovascular polypill achieved a higher reduction in SBP levels and was well tolerated. Adherence was similar to that found in the previous literature, which is remarkable given the real-life setting of our study.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

Bilateral Earlobe Creases and Subsequent Malignant Cerebral Infarction: A Patient With Diffuse Endothelial Dysfunction.

This case highlights the case of a woman in her 50´s and the association of Frank's sign with vascular disease. Earlobe crease or Frank's sign is a diagonal crease in the earlobe that extends diagonally from the tragus to the edge of the auricle with an angle of approximately 45°. Its presence increases with advancing age and is thought to be predictive of vascular disease. The recognition of this sign is considered a key factor in the identification of patients with high vascular risk and endothelial dysfunction. The association with a reperfusion syndrome, like our patient, is not known.