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Purpose: To describe corneal astigmatism in patients under the age of 55 years with Graves' ophthalmopathy and to compare it to a control group. Methods: Retrospective, nonrandomized comparative observational case series. A total of 109 patients with inactive Graves' ophthalmopathy and 109 age- and gender-matched control individuals without Graves' ophthalmopathy were examined with manual corneal keratometry. In the Graves' patients, 52% had a CT scan available for review, and 41% underwent orbital, strabismus, and/or eyelid surgery with a follow-up of keratometry over a mean period of 1.7 years after surgery. Results: For the dioptres, there was a statistically significant difference between the Graves' and the control eyes at 3-3.25 dioptres in both eyes (t-test, right eyes, P=0.042; left eyes, P=0.041). For the meridians, the astigmatism was found to be greater at the meridians 95-100 degrees (t-test, P=0.044) and 105 degrees -110 degrees (t-test, P=0.017) in the right eyes only. In 10 (9%) Graves' patients, the astigmatism had caused newly acquired reduced visual acuity. Greater astigmatism in dioptres did not correlate with specific CT scan findings (chi(2)-test, df=2, P=0.187). Following orbital, strabismus, and eyelid surgery, the dioptres and meridians of the astigmatism did not change in 56 (68%) and 66 (81%) eyes, respectively. Conclusions: Graves' ophthalmopathy may be associated with greater with-the-rule corneal astigmatism, which, overall, is not influenced by orbital, strabismus, or eyelid surgery. The astigmatism may possibly be caused by soft-tissue fibrosis in the superolateral orbital region. [ABSTRACT FROM AUTHOR]

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy., Competing Interests: Dr Mistry reports compensation from American Heart Association, AbbVie, RAPID AI, and American Heart Association for consultant services; compensation from Silver Creek Pharmaceuticals Inc and Translational Sciences for other services; employment by University of Cincinnati; and grants from National Institutes of Health, Society of Vascular and Interventional Neurology, National Institute of Neurological Disorders and Stroke, Patient-Centered Outcomes Research Institute, and National Institutes of Health. Dr Hill reports grants from Boehringer Ingelheim, Canadian Institutes of Health Research, Medtronic, and NoNO Inc; employment by University of Calgary; stock options in Basking Bioscience LLC; and compensation from Brainsgate Ltd for consultant services. Dr Coutts reports employment by Hotchkiss Brain Institute, University of Calgary. Dr Nogueira reports compensation from Anaconda Biomed, Medtronic USA Inc, Cerenovus, Genentech, Viz-AI, Prolong Pharmaceuticals, Perfuze, Biogen Inc, Shanghai Wallaby, Brainomix, Hybernia, RapidPulse, Imperative Care, Corindus Inc, NeuroVasc Technologies Inc, Corindus Vascular Robotics, Vesalio, Cerebrotech, Astrocyte, Ceretrieve, Phenox Inc, Philips, Anaconda, and Stryker Corporation for consultant services; compensation from Synchron for data and safety monitoring services; stock options in Ceretrieve, Brainomix, Corindus Inc, Perfuze, Truvic, Viz-AI, Reist/Q?Apel Medical, Vesalio, Cerebrotech, and Viseon Inc; stock holdings in Piraeus Medical, Brain4Care, and Quantanosis AI; and grants from Stryker and Cerenovus. Dr Nguyen reports compensation from Brainomix and Aruna for consultant services; and compensation from American Stroke Association for other services. Dr Medcalf reports grants from National Health and Medical Research Council. Dr Broderick reports grants from Genentech to other; compensation from Brainsgate, F. Hoffmann-La Roche, Basking Bioscience, and Kroger Prescription Plans Inc for consultant services; and grants from Novo Nordisk to other. Dr De Meyer reports grants from KU Leuven and Research Foundation Flanders. The other authors report no conflicts.

Background: Achieving first-pass recanalization (FPR) has become the primary procedural objective during thrombectomy in acute ischemic stroke patients as it correlates with the best clinical outcome. Understanding factors contributing to FPR failures is essential to enhance FPR success rates. As the central target of thrombectomy, the thrombus itself may be a significant factor influencing FPR., Objectives: This study aimed to investigate the association between thrombus composition and FPR success rates., Methods: In total, thrombi from 267 ischemic stroke patients were collected in the AZ Groeninge Hospital (Kortrijk, Belgium). Thrombus composition was determined via detailed histologic analysis of red blood cells (RBCs), fibrin, von Willebrand factor, platelets, leukocytes, citrullinated histone 3 (marker for neutrophil extracellular traps), and intracellular and extracellular DNA. FPR was defined as obtaining a modified thrombolysis in cerebral infarction (mTICI) score of 2c/3 after the first pass., Results: An mTICI score of 2c/3 was obtained in 180 patients, which was achieved via a successful FPR procedure in 126 cases or after multiple passes in 54 cases. Interestingly, thrombi from FPR cases had a different composition from thrombi that needed multiple passes to obtain an mTICI score of 2c/3. FPR thrombi contained significantly more RBCs (P = .0264), less fibrin (P = .0196), and less extracellular DNA (P = .0457)., Conclusion: Our results indicate that thrombi characterized by lower RBC content, higher fibrin levels, and increased extracellular DNA are less likely to result in an FPR. These results are important to guide future research aiming at improving procedures or technologies to obtain FPR rates in RBC-poor thrombi., Competing Interests: Declaration of competing interests P.V. received speaker fees from Boehringer-Ingelheim, BMS, Pfizer, Daiichi-Sankyo, and Medtronic. T.A. holds equity for Cereflo Ltd and is a consultant for Anaconda, Cerenovus/Neuravi, Optimize Neurovascular, and Rapid Medical. O.F. is a consultant for iVascular. All other authors have no conflicting interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ischemic stroke is caused by a thrombus blocking one or multiple arteries in the brain, resulting in irreversible damage in the associated brain tissue. The aim of therapy is to restore the blood flow as fast as possible. Two recanalization strategies are currently available: pharmacological thrombolysis using recombinant tissue plasminogen activator (rt-PA) and mechanical removal of the thrombus. Despite recent advancements, achieving efficient recanalization remains a challenge. The precise causes of therapy failure are not fully understood but thrombus composition is likely a key factor in successful recanalization. This review explores acute ischemic stroke thrombus composition, its recently identified components, and how it affects stroke treatment. It also discusses how new insights could enhance current recanalization strategies for ischemic stroke patients., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance., Methods: Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology., Results: Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi., Conclusions: Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine., Competing Interests: Disclosures Dr François is a consultant for iVascular. Dr Vanacker received speaker fees from Boehringer-Ingelheim, BMS, Pfizer, Daiichi-Sankyo, and Medtronic. Dr Andersson holds equity for Cereflo Ltd and is a consultant for Anaconda, Cerenovus/Neuravi, Optimize Neurovascular and Rapid medical. The other authors report no conflicts.

Hazardous alcohol use is one of the leading risk factors for morbidity and mortality in the world. Early identification and brief interventions (EIBIs) delivered in primary care is an effective but underutilized strategy to address this issue. Community-oriented strategies (COS) are suggested to facilitate EIBI delivery. COS are public health activities directed to the general population raising awareness and encouraging behaviour change. Unfortunately, it remains unclear what these COS should comprise and what their added value might be in EIBI delivery. To map the available information on COS aiming to facilitate alcohol-related EIBI delivery in general practice. A scoping review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping reviews guidelines, was used to map both grey and peer-reviewed literature. Of the 6586 information sources screened, 8 sources were retained in this review. Three COS are currently described in the literature, all with their different components. They include the use of mass media, self-assessment tools and waiting room actions. Waiting room actions comprising audio recordings or computerized self-assessment tools significantly increase the discussion on alcohol use in primary care. The effect of mass media and community-wide self-assessment tools on EIBI delivery remains to be determined. Currently, the described COS lack empirical justification to motivate their added value in facilitating EIBI delivery. However, a theoretical reflection showed the use of a limited set of behaviour change techniques, which might support the use of COS. There remains a lot of possible strategies to explore. This review highlights the current evidence gap and discusses the next steps., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Several studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1-2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited., Objectives: To characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy., Methods: One-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected., Results: We identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich ( n = 3), adipocyte-like pattern-rich ( n = 2), collagen-rich ( n = 2) and myxomatous ( n = 1) thrombi were also identified and are discussed with regard to pathogenesis and clinical and intervention characteristics. Finally, a thrombus with parts of a vascular wall is described. Suggestions for future studies are made and clinical and technical aspects of the management for these rare but important patients are discussed., Conclusion: In our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aspegren, Staessens, Vandelanotte, Desender, Cordonnier, Puy, Bricout, De Meyer, Andersson and Arnberg.)

Background: Hazardous alcohol use significantly affects health and wellbeing in society. General practitioners (GPs) are uniquely positioned to address this problem by integrating early identification and brief intervention (EIBI) in daily practice. Unfortunately, EIBI implementation remains low. Community-oriented strategies (COS), defined as public health activities directed to the general population, are suggested to address this implementation gap. COS aim to increase the understanding, engagement and empowerment within the population to facilitate EIBI delivery. However, no consensus on what COS should contain exists., Objectives: To obtain insight in the stakeholders' perspectives and create consensus with them on COS with the highest potential to facilitate EIBI delivery., Methods: Four nominal group sessions were conducted with 31 stakeholders representing 12 different stakeholder groups from Leuven (Belgium). Stakeholders generated ideas, reflected on them in group and prioritised them anonymously, creating four separate lists. Merging these lists with their relative scores resulted in a master list, which was checked for accuracy through a member check. Qualitative content analysis on the stakeholder's notes provided an in-depth exploration of their perspectives., Results: Twenty-one strategies were identified, nine of which were COS. Highlighting the GPs' proactive role was considered most relevant. Other foci included creating awareness on the effects of alcohol use and normalising discussing alcohol use within the community. A holistic approach, exceeding the sole focus on COS, combining community, healthcare and government was accentuated., Conclusion: Stakeholders emphasise addressing the proactive role of GPs as most promising COS, though it should be delivered within a holistic multi-component approach.

Purpose: To report a case of ablepharon-macrostomia syndrome and surgical treatment options., Methods: Case report and literature review., Results: A prematurely born male baby presented with severe ablepharon, hypertelorism, macrostomia, low-set dysplastic ears, broad nasal bridge, coarse and redundant body skin, absent scalp and body hair, lax abdominal wall, absent nipples, camptodactyly, and ambiguous genitalia. Despite intensive ocular lubrication, severe exposure keratopathy developed within the first days after birth. The eyes were closed using masquerade flaps for 6 weeks. In a secondary procedure at the adjusted age of 3 weeks, the flaps were partially divided, and visual input and development were successfully achieved, while maintaining corneal protection., Conclusions: We present a rare case of a prematurely born infant with a severe phenotype of ablepharon-macrostomia syndrome, surgically treated with masquerade flaps to preserve corneal health and allow bilateral visual input.

Torsional diplopia may frequently accompany Graves' orbitopathy and is often not recognized. Some patients with manifest cyclotorsion do not complain of torsional diplopia because it is concealed by the large vertical and/or horizontal deviation. Torsional diplopia can occur spontaneously or appear after decompression or strabismus surgery. We discuss some interesting points arising from three cases. This will be followed by a discussion of the literature on the pathogenesis of cyclodeviation in Graves' orbitopathy.