Acute management of cerebral venous thrombosis: Indications, technique, and outcome of endovascular treatment in two high-volume centers.

INTRODUCTION: After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT. METHODS: We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients. RESULTS: We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25-28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2-17) vs 0 (0-2.7), p = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2-17) vs 1(0-3.75); p < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73-2.8, p = 0.307)]. CONCLUSIONS: EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment.

Early Mobilization Decision after an Acute Ischemic Stroke: Protocol for an Umbrella Review.

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

Introducing a multicomponent staff training intervention to reduce antipsychotic medication: Care home management pre and post intervention views of systemic impact, and preliminary RE-AIM evaluation.

OBJECTIVES: We explored views of care home managers when introducing PROCUIDA-Demencia a mixed-methods two-arm cluster randomised controlled pilot and clinical outcomes study aiming to optimise dementia care by introducing psychosocial interventions to reduce antipsychotic medication in care homes. METHOD: We undertook secondary analysis of pre and post in-depth interviews conducted in summer 2018 with not-for-profit care home managers in Mexico who were allocated to the intervention group. Transcribed data were thematically analysed. Themes were mapped out with RE-AIM quality appraisal framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) as preliminary evaluation to identify practice and future intervention development and evaluation. RESULTS: Two pre- and three post-intervention themes were constructed. Participants reported measurable positive impact; one home built a new specialist dementia care unit and others hired a psychologist and psychiatrist to sustain the changes. Antipsychotic medication was reduced for some participating residents which also minimised cost burden on family members. CONCLUSION: Funding, systemic working across families, clinical and social teams and effective systems of governance are urgently required to sustain models like PROCUIDA-Demencia. The RE-AIM preliminary evaluation outlined care home managers' long-term sustainable practice and positive impact on the dementia care system. These findings might inform staff retention strategies and care home systemic care practices. This evaluation is contributing to the Mexican Alzheimer's and other dementias plan.

Acroosteólisis y dismorfia facial: un nuevo caso de síndrome de Hajdu-Cheney / Acroosteolysis and facial dysmorphia: a new case of Hajdu-Cheney Syndrome

El síndrome de Hajdu-Cheney o síndrome acro-dento-osteo-displasia es una enfermedad rara caracterizada por osteólisis en banda de las falanges distales y dismorfia facial, entre otras manifestaciones. Describimos el caso de un varón de 45 años que consultó por dolor articular de características mecánicas en las manos, asociando dismorfia facial, alteraciones craneofaciales y deformidades digitales en telescopaje con acroosteólisis.(AU)

Hajdu-Cheney syndrome or acro-dento-osteo-dysplasia syndrome is a rare disease characterized by band osteolysis of distal phalanges and facial dysmorphia, among other manifestations. We present the case of a 45-year-old male who consulted for mechanical joint pain of both hands, facial dysmorphism, cranio-facial alterations, and digital telescoping with acroosteolysis.(AU)

Acroosteolysis and facial dysmorphia: a new case of Hajdu-Cheney syndrome.

Hajdu-Cheney syndrome or acro-dento-osteo-dysplasia syndrome is a rare disease characterized by band osteolysis of distal phalanges and facial dysmorphia, among other manifestations. We present the case of a 45-year-old male who consulted for mechanical joint pain of both hands, facial dysmorphism, cranio-facial alterations, and digital telescoping with acroosteolysis.

Interleukin-17-targeted treatment in patients with spondyloarthritis and associated cardiometabolic risk profile.

Spondyloarthritis is a group of immune-mediated rheumatic disorders that significantly impact patients' physical function and quality of life. Patients with spondyloarthritis experience a greater prevalence of cardiometabolic disorders, such as obesity, hypertension, dyslipidemia and diabetes mellitus, and these comorbidities are associated with increased spondyloarthritis disease activity and risk of cardiovascular events. This narrative review summarizes the evidence for a physiological link between inflammatory status and cardiometabolic comorbidities in spondyloarthritis, as well as the impact of interleukin (IL)-17 blockade versus other molecular mechanisms in patients with cardiometabolic conditions. The IL-23/IL-17 axis plays a pivotal role in the pathophysiology of spondyloarthritis by promoting inflammation and tissue remodeling at the affected joints and entheses. The importance of the IL-23/IL-17 signaling cascade in underlying sub-clinical inflammation in common cardiometabolic disorders suggests the existence of shared pathways between these processes and spondyloarthritis pathophysiology. Thus, a bidirectional relationship exists between the effects of biologic drugs and patients' cardiometabolic profile, which must be considered during treatment decision making. Biologic therapy may induce changes in patients' cardiometabolic status and cardiometabolic conditions may conversely impact the clinical response to biologic therapy. Available evidence regarding the impact of IL-17 blockade with secukinumab on cardiometabolic parameters suggests this drug does not interfere with traditional cardiovascular risk markers and could be associated with a decreased risk of cardiovascular events. Additionally, the efficacy and retention rates of secukinumab do not appear to be negatively affected by obesity, with some studies reporting a positive impact on clinical outcomes, contrary to that described with other approaches, such as tumor necrosis factor blockade. In this article, we also review evidence for this bidirectional association with other treatments for spondyloarthritis. Current evidence suggests that IL-17-targeted therapy with secukinumab is highly effective in spondyloarthritis patients with cardiometabolic comorbidities and may provide additional cardiometabolic benefits.

Are all ventilators for NIV performing the same? A bench analysis.

Global pandemic due to COVID-19 has increased the interest for ventilators´ use worldwide. New devices have been developed and older ones have undergone a renewed interest, but we lack robust evidence about performance of each ventilator to match appropriate device to a given patient and care environment. The aim of this bench study was to investigate the performance of six devices for noninvasive ventilation, and to compare them in terms of volume delivered, trigger response, pressurization capacity and synchronization in volume assisted controlled and pressure support ventilation. All ventilators were tested under thirty-six experimental conditions by using the lung model ASL5000® (IngMar Medical, Pittsburgh, PA). Two leak levels, two muscle inspiratory efforts and three mechanical patterns were combined for simulation. Trigger function was assessed by measurement of trigger-delay time. Pressurization capacity was evaluated as area under the pressure-time curve over the first 500 ms after inspiratory effort onset. Synchronization was evaluated by the asynchrony index and by incidence and type of asynchronies in each condition. All ventilators showed a good performance, even if pressurization capacity was worse than expected. Leak level did not affect their function. Differences were found during low muscle effort and obstructive pattern. In general, Philips Trilogy Evo/EV300 and Hamilton C3 showed the best results. NIV devices successfully compensate air leaks but still underperform with low muscle effort and obstructive lungs. Clinicians´ must have a clear understanding of the goals of NIV both for devices´ choice and set main parameters to achieve therapy success.

Cognition in older adults with healthy aging: analysis of the Mexican Health and Aging Study 2012-2015.

Introduction: Maintaining older adults' health and well-being can be achieved through the optimization of physical and mental health, while preserving independence, social participation, and quality of life. Cognitive change has been described as a normal process of aging and it involves domains such as processing speed, attention, memory, language, visuospatial abilities, and executive functioning, among others. Objective: To describe cognitive changes in older adults with healthy aging. Methods: This is a study that involved data from 14,893 and 14,154 individuals aged >60 years or older from the 2012 and 2015 waves, respectively, who participated in the Mexican Health and Aging Study (MHAS). Participants with healthy aging were identified and described in the MHAS-2012 wave and followed to 2015. Eight cognitive domains evaluated in the Cross-Cultural Cognitive Evaluation (CCCE,) as well as sociodemographic and health characteristics, were described. Criteria for healthy aging involved the following: CCCE ≥ -1.5 standard deviations above the mean on reference norms, independence on basic and instrumental activities of daily living, self-reported "life close to ideal," and preserved functional and social performance. Results: From a total of n = 9,160 older adults from the MHAS-2012 wave, n = 1,080 (11.8%) had healthy aging. In the healthy aging group, the median age was 67 years (IQR: 63-73), 58.1% were female and the median for education was 6 (IQR: 3-8) years. The mean CCCE score was 57 (SD: 16.9) points. In the MHAS-2012 cross-sectional analysis, except for orientation, visuospatial abilities, and verbal fluency, all cognitive domain scores were lower with passing age. When comparing cognitive domain scores in the 225 older adults identified with healthy aging between the 2012 and 2015 MHAS waves, there were almost no observable differences. Conclusion: In the cross-sectional analysis, Mexican adults with healthy aging had lower scores in the verbal learning memory, visual scanning, numeracy, visual memory, and verbal recall domains', as well as lower global cognitive scores in the higher age groups. There were no cognitive changes in the 3 year follow-up, except for a lower gradient of scores in the verbal recall memory domain. Longer prospective studies are needed to characterize greater cognitive changes.

Sedation with Sevoflurane versus Propofol in COVID-19 Patients with Acute Respiratory Distress Syndrome: Results from a Randomized Clinical Trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) related to COVID-19 (coronavirus disease 2019) led to intensive care units (ICUs) collapse. Amalgams of sedative agents (including volatile anesthetics) were used due to the clinical shortage of intravenous drugs (mainly propofol and midazolam). METHODS: A multicenter, randomized 1:1, controlled clinical trial was designed to compare sedation using propofol and sevoflurane in patients with ARDS associated with COVID-19 infection in terms of oxygenation and mortality. RESULTS: Data from a total of 17 patients (10 in the propofol arm and 7 in the sevoflurane arm) showed a trend toward PaO2/FiO2 improvement and the sevoflurane arm's superiority in decreasing the likelihood of death (no statistical significance was found). CONCLUSIONS: Intravenous agents are the most-used sedative agents in Spain, even though volatile anesthetics, such as sevoflurane and isoflurane, have shown beneficial effects in many clinical conditions. Growing evidence demonstrates the safety and potential benefits of using volatile anesthetics in critical situations.

Evaluation of functional warm ischemia time during controlled donation after circulatory determination of death using normothermic regional perfusion (ECMO-TT): A prospective multicenter cohort study.

BACKGROUND: Controlled donation after circulatory determination of death (cDCD) seems an effective way to mitigate the critical shortage of available organs for transplant worldwide. As a recently developed procedure for organ retrieval, some questions remain unsolved such as the uncertainty regarding the effect of functional warm ischemia time (FWIT) on organs´ viability. METHODS: We developed a multicenter prospective cohort study collecting all data from evaluated organs during cDCD from 2017 to 2020. All the procedures related to cDCD were performed with normothermic regional perfusion. The analysis included organ retrieval as endpoint and FWIT as exposure of interest. The effect of FWIT on the likelihood for organ retrieval was evaluated with Relative distribution analysis. RESULTS: A total amount of 507 organs´ related information was analyzed from 95 organ donors. Median donor age was 62 years, and 63% of donors were male. Stroke was the most common diagnosis before withdrawal of life-sustaining therapy (61%), followed by anoxic encephalopathy (21%). This analysis showed that length of FWIT was inversely associated with organ retrieval rates for liver, kidneys, and pancreas. No statistically significant association was found for lungs. CONCLUSIONS: Results showed an inverse association between functional warm ischemia time (FWIT) and retrieval rate. We also have postulated optimal FWIT's thresholds for organ retrieval. FWIT for liver retrieval remained between 6 and less than 11 min and in case of kidneys and pancreas, the optimal FWIT for retrieval was 6 to 12 min. These results could be valuable to improve organ utilization and for future analysis.

Diagnostic accuracy of CT angiography and CT perfusion imaging for detecting distal medium vessel occlusions: Protocol for a systematic review and meta-analysis.

BACKGROUND: Distal medium vessel occlusions (DMVOs) represent 25-40% of all acute ischemic strokes (AIS). DMVO clinical syndromes are heterogenous, but as eloquent brain regions are frequently involved, they are often disabling. Since current intravenous fibrinolytic therapies may fail to recanalize up to two-thirds of DMVOs, endovascular treatment is progressively being considered in this setting. Nevertheless, the optimal imaging method for diagnosis remains to be defined. Stroke centers that use computed tomography as a routine stroke imaging approach rely on either isolated computed tomography angiography (CTA) or combined perfusion (CTP) studies. Despite a simplified non-CTP-dependent approach seeming reasonable for large vessel occlusion AIS diagnosis, CTP may still hold advantages for DMVOs workup. Therefore, this systematic review aims to compare the diagnostic performance of CTA and CTP in detecting DMVOs. METHODS: We will perform a systematic search in PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include any type of study that presents data on the diagnostic accuracy of CTA and/or CTP for detecting DMVOs. Two authors will independently review retrieved studies, and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. Data will be combined in a quantitative meta-analysis following the guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: This will be the first systematic review and meta-analysis that compares two different imaging approaches for detecting DMVOs. This study may help to define optimal acute ischemic stroke imaging work-up. TRIAL REGISTRATION: PROSPERO registration: CRD42022344006.

The evolution of blood-brain barrier permeability changes after stroke and its implications on clinical outcome: A systematic review and meta-analysis.

BACKGROUND: Blood-brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke. AIMS: The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes. METHODS: We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method. RESULTS: We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48-0.99), 1.68 (0.94-2.42), 1.98 (0.96-3.00), and 1.00 (0.45-1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase. CONCLUSION: BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.

Reconsidering the role of blood-brain barrier in Alzheimer's disease: From delivery to target.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-ß. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

Differentiated Effect of Smoking on Disease Activity and Quality of Life among Different Spondyloarthritis Phenotypes.

BACKGROUND AND AIMS: The effect of smoking on disease activity and quality of life (QoL) in spondyloarthritis (SpA) is far from clear. We aimed to evaluate the relationship between smoking and these outcomes in patients with axial SpA (axSpA) and psoriatic arthritis (PsA). PATIENTS AND METHODS: This cross-sectional observational multicenter study included 242 patients with axSpA and 90 with PsA. The association between conventional cardiovascular risk factors and disease activity as well as QoL, in both SpA phenotypes was evaluated. For this, univariate and multivariate regression analyses were performed, as well as confirmatory meta-analyses. RESULTS: Regardless of age, sex, or disease duration, patients with axSpA showed significantly less association with obesity (OR 0.50 (0.26-0.96), p = 0.03) and hypertension (OR 0.33 (0.18-0.62), p = 0.0005). However, axSpA was significantly associated with smoking (OR 2.62 (1.36-5.04), p = 0.004). Patients with axSpA were more likely to be in a category of high disease activity compared with PsA (OR 2.86, p = 0.0006). Regardless of sex, age, disease duration, and education level, smoking was significantly associated with higher disease activity in axSpA (OR 1.88, p = 0.027). A fixed-effects model meta-analysis (OR 1.70, p = 0.038) confirmed the association between tobacco and disease activity. No relationship was found between smoking (or other cardiometabolic risk factors) and structural damage or worse QoL in either disease. CONCLUSIONS: Although the cardiometabolic risk profile is clearly different between both SpA phenotypes, the only clear link between these factors and increased disease activity was observed between smoking and axSpA. Our findings need further confirmation.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages.

OBJECTIVE: Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis. METHODS: IgG and IgM serum levels of antibodies against HDL (anti-HDL) and apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients, 14 arthralgia individuals and 96 controls. Established RA patients (n = 42) were included for validation. Atherosclerosis and vascular stiffness were measured by Doppler ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high-throughput targeted proteomics. RESULTS: Anti-HDL and anti-ApoA1 responses were increased in early RA compared with controls (both P < 0.001) and were comparable to established disease. Only anti-ApoA1 antibodies were increased in arthralgia. IgG anti-HDL and anti-ApoA1 were associated with unfavourable lipoprotein traits in RA and arthralgia, respectively. A similar picture was observed for inflammatory mediators. No associations with clinical features or risk factors were found. IgG anti-HDL were independently associated with atherosclerosis occurrence in early RA, and outperformed patient stratification over conventional algorithms (mSCORE) and their anti-ApoA1 counterparts. Anti-HDL antibodies correlated with proteins involved in immune activation, remodelling and lipid metabolism pathways in early RA. CONCLUSION: Humoral responses against HDL particles are an early event along the arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers and underlying pathogenic circuits.

Therapeutic Lying as a Non-Pharmacological and Person-Centered Approach in Dementia for Behavioral and Psychological Symptoms of Dementia.

The acceptance and ethics behind therapeutic lying (TL) as a non-pharmacological intervention for behavioral and psychological symptoms of dementia (BPSD) among persons with dementia continues to generate heated debates. This article presents a discussion of the ethical and cultural challenges on the perception of TL by people with dementia, their families, and health care professionals. Additionally, decision-making before TL was analyzed, including the types of TL, its efficacy and implications, alternatives to TL, and the ethical principles behind it. The results from this analysis show that TL is a common practice for BPSD. Its benefits include the reduction of these symptoms as well as the use of physical or chemical restraints. However, there is no consensus on its suitability as an approach, nor on the appropriate way it should be used. More experimental studies are needed to create legal and clinical intervention protocols that respect the fundamental rights of people with dementia promoting coherence, good ethical practices, and guidelines for person-centered care.