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Background: The procedure of middle meningeal artery embolization (MMAE) has emerged as a minimally invasive therapy for chronic subdural hematoma (CSDH). Previous studies comparing MMAE with conventional treatment for CSDH did not differentiate primary/upfront, adjunct, or rescue MMAE, and included both conservative and surgical treatment in the comparison group. We conducted a systematic review and meta-analysis to compare outcomes after adjunct MMAE (MMAE combined with surgical evacuation) versus surgery alone for CSDH., Methods: PubMed, Embase, Cochrane, Web of Science, and Scopus databases were searched to August 2023. Primary outcomes were treatment failure and reoperation. Secondary outcomes were complications, mortality, length of hospital stay, 30-day readmission, and follow-up modified Rankin Scale (mRS) > 2. Additional data from our institution was included., Results: 12 published studies and our data yielded 57,165 patients, of whom 1,065 (1.9%) received adjunct MMAE and 56,100 (98.1%) surgery alone. Compared to surgery alone, adjunct MMAE was associated with lower rates of treatment failure (OR = 0.43 [0.23-0.83], p = 0.01), reoperation (OR = 0.45 [0.22-0.90], p = 0.02), and 30-day readmission (OR = 0.50 [0.34-0.73], p < 0.001). Length of hospital stay (MD = 2.49 [-0.51, 5.49], p = 0.10) was non-significantly longer in the adjunct MMAE group. Both groups had comparable rates of treatment-related complications (OR = 0.89 [0.52-1.53], p = 0.67), mortality (OR = 1.05 [0.75-1.46], p = 0.78), and follow-up mRS > 2 (OR = 0.91 [0.39-2.12], p = 0.83)., Conclusions: Adjunct MMAE reduces treatment failure, reoperation, and readmission rates without increasing morbidity and mortality. MMAE may be considered as an adjunct to surgical evacuation to reduce CSDH recurrence. Randomized trials will further establish the evidence for adjunct MMAE and its role in the management of CSDH., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. The retrospective review of clinical data was approved by the local institutional review board, with a waiver of informed consent. Consent to participate: Written informed consent was obtained from the participants prior to all procedures. A waiver of informed consent was granted by the institutional review board for retrospective review of the clinical data due to minimal risk to participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes. EVT requires the close coordination of multiple departments and poses unique challenges to care coordination in large hospitals. We present the results of our quality improvement project that aimed to improve our door-to-groin puncture (DTP) times for patients who undergo EVT after direct presentation to our emergency department., Methods: We conducted time-motion studies to understand the full process of an EVT activation and conducted Gemba walks in multiple hospitals. We also reviewed the literature and interviewed stakeholders to create interventions that were implemented over 4 Plan-Do-Study-Act (PDSA) cycles. We retrospectively collected data starting from baseline and during every PDSA cycle. During each cycle, we studied the impact of the interventions, adjusted the interventions, and generated further interventions. A variety of interventions were introduced targeting all aspects of the EVT process. This included parallel processing to reduce waiting time, standardization of protocols and training of staff, behavioral prompts in the form of a stroke clock, and push systems to empower staff to facilitate the forward movement of the patient. A novel role-based communication app to facilitate group communications was also used., Results: Eighty-eight patients spanning across 22 months were analyzed. After the final PDSA cycle, the median DTP time was reduced by 36.5% compared with baseline (130 minutes (interquartile range [IQR] 111-140) to 82.5 minutes (IQR 74.8-100)). There were improvements in all phases of the EVT process with the largest time savings occurring in EVT decision to patient arrival at the angiosuite. Interventions that were most impactful are described., Discussion: EVT is a complex process involving multiple processes and local factors. Analysis of the process from all angles and intervening on multiple small aspects can add up to significant improvements in DTP times., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Paediatric neurovascular anomalies associated with the vein of Galen (VG) comprise of a spectrum of rare, complex, and life-threatening conditions. In this group, the "vein of Galen aneurysmal dilatation" (VGAD) is a distinct entity that often presents with progressive neurological symptoms in older children. Acute haemorrhage in VGAD is uncommon. We present an unusual presentation of VGAD in a neonate and discuss the challenges faced in the management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The prevalence of pain among cancer patients vary in the cancer trajectory and nurses will encounter patients with cancers who may experience pain. Nurses routinely need to assess and manage pain to deliver quality care., Aim and Method: The study aims to understand the knowledge and attitudes of nurses towards pain management using the self-administered questionnaire-the Knowledge and Attitude Survey Regarding Pain (KASRP)., Findings: Some 80 nurses participated in the study with an average overall KASRP score of 56%. Areas that were poorly answered are related to the knowledge about opioids, assessment of pain and management of pain in different scenarios. Factors like nurse-patient relationships and being unfamiliar with opioids may affect the knowledge and attitude of nurses towards pain management., Conclusion: Curriculum on pain management needs to consider strategies to help nurses translate knowledge to bedside clinical teaching. It needs to include facts of pain management, and topics regarding self-awareness and clarifying misconceptions.

Background: A carotid-cavernous fistula is an abnormal communication between the arteries and veins within the cavernous sinus. While conservative management may be prudent in low risk cases, many patients require intervention and endovascular embolization has evolved as the preferred method of treatment. Embolization can be performed via either the transarterial or transvenous approach. One major challenge of the transvenous approach is the complex and variable compartmentation of the cavernous sinus, which often requires the use of low profile microcatheters to navigate and reach the fistulous point. Fibered coils are also preferred when performing transvenous embolization of carotid-cavernous fistula, as they are of higher thrombogenicity and allow for faster occlusion of the fistula. However, most low profile (0.017-inch) microcatheters are not able to deploy fibered coils based on the manufacturer's instructions., Case Presentation: We present two successful cases of off-label use of Medtronic Concerto fibered coils via a 0.017-inch microcatheter during transvenous embolization of carotid-cavernous fistula in a 60-year-old and an 80-year-old Chinese female, respectively., Conclusion: Our case series highlight the possibility of deploying large diameter (up to 10 mm) Concerto fibered coils through a low profile (0.017-inch) microcatheter in an off-label manner for transvenous embolization of indirect carotid-cavernous fistula., (© 2024. The Author(s).)

A novel baculovirus observed to infect Automeris liberia (Cramer) (bullseye moth) is here described. Caterpillars of A. liberia with symptoms of viral infection were collected from African oil palm plantations in Tailândia, PA, Brazil. Macerated caterpillars were then offered to caterpillars of Automeris cinctistriga (Felder & Rogenhoper), leading to viral symptoms and death before pupation. A transmission electron microscope was used for virus ultrastructural identification. The presence of viral occlusion bodies (OBs) containing multiple nucleocapsids was observed and such features are compatible with Alphabaculovirus (Baculoviridae). Molecular detection by PCR with primers for polyhedrin gene (polh) and for late expression factor-8 gene (lef-8), confirmed that this isolate belonged to Alphabaculovirus genus. To our knowledge, this is the first record of a baculovirus isolated from or associated to Automeris. The name Automeris liberia nucleopolyhedrovirus (AuliNPV) is proposed for the new virus., (© 2022. Sociedade Entomológica do Brasil.)

In an era of rapidly expanding knowledge and sub-specialization, it is becoming increasingly common to focus on one organ system. However, the human body is intimately linked, and disease processes affecting one region of the body not uncommonly affect the other organ systems as well. Understanding diseases from a macroscopic perspective, rather than a narrow vantage point, enables efficient and accurate diagnosis. This tenet holds true for diseases affecting both the thoracic and neurological systems; in isolation, the radiologic appearance of disease in one organ system may be nonspecific, but viewing the pathophysiologic process in both organ systems may markedly narrow the differential considerations, and potentially lead to a definitive diagnosis. In this article, we discuss a variety of disease entities known to affect both the thoracic and neurological systems, either manifesting simultaneously or at different periods of time. Some of these conditions may show neither thoracic nor neurological manifestations. These diseases have been systematically classified into infectious, immune-mediated / inflammatory, vascular, syndromic / hereditary and neoplastic disorders. The underlying pathophysiological mechanisms linking both regions and radiologic appearances in both organ systems are discussed. When appropriate, brief clinical and diagnostic information is provided. Ultimately, accurate diagnosis will lead to expedited triage and prompt institution of potentially life-saving treatment for these groups of complex disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Contraceptive implant migration into the pulmonary circulation is an uncommon, but potentially serious complication. We describe an "aspiration" technique for percutaneous retrieval of a contraceptive implant from a subsegmental pulmonary artery, using a Penumbra Neuron MAX 088 guiding catheter and a Merit Medical VacLok Vacuum Pressure Syringe, as an alternative to the previously described snare technique. Our patient had an uneventful recovery and was discharged home on the same day., (© 2020 Published by Elsevier Inc. on behalf of University of Washington.)

Hypoxia-inducible factors (HIFs) facilitate cellular adaptation to environmental stress such as low oxygen conditions (hypoxia) and consequently promote tumor growth. While HIF-1α functions in cancer progression have been increasingly recognized, the contribution of HIF-2α remains widely unclear despite accumulating reports showing its overexpression in cancer cells. Here, we report that HIF-2α up-regulates the expression of CD70, a cancer-related surface antigen that improves anchorage-independent growth in cancer cells and is associated with poor clinical prognosis, which can be induced via epigenetic modifications mediated by DNMT1. The ablation of CD70 by RNAi led to decreased colony forming efficiency in soft agar. Most strikingly, we identified the emergence of CD70-expressing cells derived from CD70-negative cell lines upon prolonged hypoxia exposure or DNMT1 inhibition, both of which significantly reduced CpG-nucleotide methylations within CD70 promoter region. Interestingly, DNMT1 expression was decreased under hypoxia, which was rescued by HIF-2α knockdown. In addition, the expression of CD70 and colony forming efficiency in soft agar were decreased by knockdown of HIF-2α. These findings indicate that CD70 expression and an aggressive phenotype of cancer cells is driven under hypoxic conditions and mediated by HIF-2α functions and epigenetic modifications. This provides additional insights into the role of HIF-2α in coordinated regulation of stem-like functions and epigenetics that are important for cancer progression and may present additional targets for the development of novel combinatorial therapeutics., Competing Interests: CONFLICTS OF INTEREST None.

The wound-healing assay is efficient and one of the most economical ways to study cell migration in vitro. Conventionally, images are taken at the beginning and end of an experiment using a phase-contrast microscope, and the migration abilities of cells are evaluated by the closure of wounds. However, cell movement is a dynamic phenomenon, and a conventional method does not allow for tracking single-cell movement. To improve current wound-healing assays, we use live-cell imaging techniques to monitor cell migration in real time. This method allows us to determine the cell migration rate based on a cell tracking system and provides a clearer distinction between cell migration and cell proliferation. Here, we demonstrate the use of live-cell imaging in wound-healing assays to study the different migration abilities of breast epithelial cells influenced by the presence of TIP60. As cell motility is highly dynamic, our method provides more insights into the processes of wound healing than a snapshot of wound closure taken with the traditional imaging techniques used for wound-healing assays.

Objectives: To investigate the independent predictors of medication adherence among Singaporean patients following an ischaemic stroke or transient ischaemic attack., Background: Secondary prevention of stroke includes optimal control over modifiable risk factors, and medication adherence is important in controlling the effect of comorbidities. However, there is a paucity of published literature on the topics of medication adherence among stroke patients, especially in the Asian population., Design: A cross-sectional, descriptive, correlational study., Methods: One hundred and twenty-one patients with ischaemic stroke or transient ischaemic attack were recruited from a tertiary hospital in Singapore. Data collection included the Morisky Medication Adherence Scale-8 (MMAS-8), General Self-Efficacy Survey (GSES) and Medical Outcome Study Social Support Survey. Multiple linear regression analyses were used to evaluate predictors of medication adherence, measured by MMAS-8., Results: The mean score of the MMAS-8 was 5.07 (SD = 2.20, range 0-8), and more than 80% of the participants had low (n = 65, 53.7%) or medium (n = 34, 28.1%) levels of medication adherence. Multivariate linear regression analysis showed that two factors, namely "understanding the benefits of medications" (β = 0.238, p = .010) and "having suffered from stroke twice or more" (β = 0.235, p = .014), were identified as independent predictors of medication adherence in stroke patients while the other variables were adjusted. These two factors accounted for 12.4% of the variance., Conclusion: Medication adherence was poor in Singaporean patients following an ischaemic stroke or transient ischaemic attack. The independent predictors identified in this study will support healthcare professionals to develop tailored intervention to improve medication adherence among this group of patients., Relevance to Clinical Practice: Nurses play an important role in promoting patients' medication adherence. Helping stroke patients understand the long-term benefits of their medications is essential to enhance patients' medication adherence and results in better health outcomes., (© 2017 John Wiley & Sons Ltd.)

Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood. To identify and quantify hypoxia-induced alternative splicing events in human cancer cells, we performed whole transcriptome RNA-Seq in breast cancer cells that are known to provide robust transcriptional response to hypoxia. We found 2005 and 1684 alternative splicing events including intron retention, exon skipping and alternative first exon usage that were regulated by acute and chronic hypoxia where intron retention was the most dominant type of hypoxia-induced alternative splicing. Many of these genes are involved in cellular metabolism, transcriptional regulation, actin cytoskeleton organisation, cancer cell proliferation, migration and invasion, suggesting they may modulate or be involved in additional features of tumorigenic development that extend beyond the known functions of canonical full-length transcripts.

Hoarseness secondary to an anterior condylar confluence (ACC) dural arteriovenous fistula (DAVF) has not been previously described. We present a 58-year-old patient with a 3-week history of progressive unilateral left-sided headaches and hoarseness. Nasolaryngoscopy and CT neck showed the presence of unilateral vocal cord palsy with no identifiable cause along the expected course of the recurrent laryngeal nerve. MRI revealed an incidental finding of abnormal serpiginous vessels in the left hypoglossal canal which led to a diagnostic cerebral angiogram, confirming the presence of an ACC DAVF. The patient underwent transvenous coil embolisation with subsequent resolution of arteriovenous shunting and symptoms. Follow-up MRI at 6 months showed no recurrence and there was complete resolution of clinical symptoms., (2017 BMJ Publishing Group Ltd.)

R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8 + T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1α)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8 + T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1α stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8 + T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function., Competing Interests: The authors declare no conflict of interest.

Objective: To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC)., Summary Background Data: Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear., Methods: Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS., Results: Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI-), (Milan+, McVI+), (Milan-, McVI-), and (Milan-, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI-) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan-, McVI-) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan-, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information., Conclusions: McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.