Antimicrobial immunity impedes CNS vascular repair following brain injury.

Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood-brain barrier leakage and a failure to restore cognitive-motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.

Venous-plexus-associated lymphoid hubs support meningeal humoral immunity.

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system1,2. The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development3-6. Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

Quantification of hematoma and perihematomal edema volumes in intracerebral hemorrhage study: Design considerations in an artificial intelligence validation (QUANTUM) study.

BACKGROUND: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. METHODS/DESIGN: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. DISCUSSION: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Effects of hyperoxemia on aneurysmal subarachnoid hemorrhage outcomes: a systematic review and meta-analysis.

OBJECTIVE: In recent years, hyperoxemia in the intensive care unit has received attention as potentially contributing to negative outcomes in the setting of cardiac arrest, ischemic stroke, and traumatic brain injury. The authors sought to evaluate whether hyperoxemia contributes to worse outcomes in the setting of aneurysmal subarachnoid hemorrhage (aSAH) and to summarize suggested pathophysiological mechanisms. METHODS: A systematic literature review was conducted without date restrictions on the PubMed and Web of Science databases on September 15, 2021. All studies that assessed the relationship between patients treated for aSAH and hyperoxemia were eligible independent of the criteria used to define hyperoxemia. All nonclinical studies and studies that did not report outcome data specific to patients with aSAH were excluded. A total of 102 records were found and screened, resulting in assessment of 10 full-text studies, of which 7 met eligibility criteria. Risk of bias was assessed using the Downs and Black checklist. A meta-analysis on the pooled 2602 patients was performed, and forest plots were constructed. Additionally, a review of the literature was performed to summarize available data regarding the pathophysiology of hyperoxemia. RESULTS: The included studies demonstrated an association between hyperoxemia and increased morbidity and mortality following aSAH. The criteria used to determine hyperoxemia varied among studies. Pooling of univariate data showed hyperoxemia to be associated with poor neurological outcome (OR 2.26, 95% CI 1.66-3.07; p < 0.001), delayed cerebral ischemia (DCI) (OR 1.91, 95% CI 1.31-2.78; p < 0.001), and increased incidence of poor neurological outcome or mortality as a combined endpoint (OR 2.36, 95% CI 1.87-2.97; p < 0.001). Pooling of multivariable effect sizes showed the same relationship for poor neurological outcome (OR 1.28, 95% CI 1.07-1.55; p = 0.01) and poor neurological outcome and mortality as a combined endpoint (OR 1.17, 95% CI 1.11-1.23; p < 0.001). Additionally, review of preclinical studies underlined the contribution of oxidative stress due to hyperoxemia to acute secondary brain injury and DCI. CONCLUSIONS: Reported outcomes from the available studies have indicated that hyperoxemia is associated with worse neurological outcome, mortality, and DCI. These findings provide a general guideline toward avoiding hyperoxemia in the acute setting of aSAH. Further studies are needed to determine the optimal ventilation and oxygenation parameters for acute management of this patient population.

Direct carotid puncture for neuroendovascular procedures.

BACKGROUND: Classically, access for neuroendovascular procedures is facilitated via groin or wrist puncture, entering the femoral or radial artery, respectively. However, in some instances, adequate intracranial access is not obtainable with those approaches due to vessel tortuosity or unfavorable anatomy. We describe a thrombectomy for stroke that was complicated by inability to achieve intracranial access via standard approaches. METHOD: To circumvent difficulties obtaining intracranial access, we entered the arterial circulation via a direct carotid puncture. CONCLUSION: Direct carotid puncture is an alternative access route for neuroendovascular procedures when intracranial access is not achievable by femoral or radial approaches due to unfavorable vascular anatomy.

Experimental animal models for the study of moyamoya disease.

Moyamoya disease is a rare disorder of the cerebrovascular system affecting individuals in a bimodal age distribution and is characterized by progressive vascular stenosis of the bilateral supraclinoid internal carotid arteries with compensatory formation of collateral vessels at the base of the brain. Despite the disease's initial description in the literature in 1957, little progress has been made in the development of medical and surgical therapeutics due to, in no small part, the lack of effective experimental animal models. Currently, there is a poor understanding of the pathophysiological mechanisms behind the development of the moyamoya vasculopathies. Since the description of a genetic association between moyamoya disease, few studies have investigated the impact of genetic manipulation on the development of an animal model for experimentation. To date, no one model recapitulates the precise phenotype of the moyamoya vasculopathies, although development of an appropriate model would allow for an in-depth investigation into the pathological mechanisms underlying the disease. In this review, the authors discuss the immunological, mechanical, and genetic methods used to develop moyamoya experimental models, as well as future perspectives.

Gamma Knife Radiosurgery for Trigeminal Neuralgia Reduces Neurovascular Compression: A Case Report after 11 Years.

BACKGROUND: Trigeminal neuralgia (TN) is a rare and debilitating craniofacial pain syndrome often caused by vascular compression of the trigeminal nerve. Gamma Knife radiosurgery (GKRS) has been shown to offer a less invasive yet effective treatment method for pain reduction in TN. In this case report, we observed radiological evidence of resolved neurovascular compression after 11 years for a patient with recur-rent TN and prior GKRS. CASE REPORT: A 72-year-old -female presented with TN and radiological evidence of neurovas-cular compression on the affected side. She had complete resolution of her pain for 7 years after treatment with GKRS. The patient experienced recurrence and underwent repeat GKRS, this time resulting in another 3 years of pain relief. After the second recurrence, repeat intracranial imaging demonstrated resolution of neurovascular compression. DISCUSSION: GKRS is an important treatment option for TN, although the mechanisms behind pain relief from this procedure still remain unclear. While prior histological and radiological studies point to ablative mechanisms for pain relief, this case report suggests that GKRS may result in a decompressive effect in TN due to changes in neurovascular architecture. Despite this finding, TN is known to occur and recur in the absence of neurovascular compression; thus, further work is necessary to understand the etiology of TN and its treatments. CONCLUSION: In this case, we demonstrate that vessel-nerve relationships may change over time in TN patients treated with GKRS, which raises the possibility that GKRS could ease a neurovascular compression.

Ganglioglioma Arising from the Septum Pellucidum: Case Report and Review of the Literature.

BACKGROUND: Gangliogliomas are low-grade neoplasms that typically affect patients under the age of 30 and present with epilepsy and symptoms of mass effect. Here, we report a case of an intraventricular ganglioglioma involving the septum pellucidum in a pediatric patient with history of optic glioma. Only one other pediatric intraventricular ganglioglioma arising from the septum pellucidum has been reported previously. CASE REPORT: The patient initially presented at 9 months of age with a pilocytic astrocytoma centered on the optic chiasm, treated with chemotherapy and radiation at 3 years of age. Routine follow-up imaging at 13 years of age revealed the development of a mass in the septum pellucidum, which was subtotally resected endoscopically because of its proximity to the fornices. Pathology confirmed a ganglioglioma positive for the BRAF V600E mutation. The tumor residual progressed and was treated with stereotactic radiosurgery. The patient was asymptomatic at her 6-month follow-up visit and the size of the nodule remained stable. LITERATURE REVIEW: Our review of the 25 previously reported intraventricular gangliogliomas found that their pre-surgical diagnoses were often incorrect, reflecting the difficulty of making the diagnosis with signs, symptoms, and imaging alone. Patients can be reassured that the prognosis is generally favorable following uncomplicated neurosurgical resection.

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(ß-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model.

Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy. Here, we introduce a two-pronged treatment strategy, composed of MR image-guided focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides widespread but targeted GDNF transgene expression in the brain following systemic administration. MR image-guided FUS allows circulating gene vectors to partition into the brain tissue by noninvasive and transient opening of the blood-brain barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN provide widespread and uniform GDNF expression throughout the targeted brain tissue. After only a single treatment, our strategy led to therapeutically relevant levels of GDNF protein content in the FUS-targeted regions in the striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10 weeks. Importantly, our strategy restored both dopamine levels and dopaminergic neuron density and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of local or systemic toxicity. Our combinatorial approach overcomes limitations of current delivery strategies, thereby potentially providing a novel means to treat PD.

Systemic PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by eliminating activated hepatic stellate cells.

UNLABELLED: Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration-approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and/or reverse liver fibrogenesis/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half-life. To overcome this problem, we previously generated PEGylated TRAIL (TRAILPEG ) that has a much longer half-life in rodents than native-type TRAIL. In this study, we demonstrate that intravenous TRAILPEG has a markedly extended half-life over native-type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAILPEG directly induces apoptosis of aHSCs in vivo and ameliorates carbon tetrachloride-induced fibrosis/cirrhosis in rats by simultaneously down-regulating multiple key fibrotic markers that are associated with aHSCs. CONCLUSION: TRAIL-based therapies could serve as new therapeutics for liver fibrosis/cirrhosis and possibly other fibrotic diseases. (Hepatology 2016;64:209-223).

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain.

Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low-resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure-driven flow provided by convection-enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus-based or synthetic nonbiodegradable systems. Using a state-of-the-art biodegradable polymer, poly(ß-amino ester), colloidally stable sub-100 nm DNA nanoparticles are engineered with a nonadhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain-penetrating nanoparticles are able to homogeneously distribute throughout the rodent striatum and mediate widespread and high-level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. METHODS: We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. RESULTS: We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). CONCLUSION: Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

Comparison of PED/PED Flex and PED Shield in the treatment of unruptured intracerebral aneurysms.

OBJECTIVE: The object of this study was to compare the efficacy and safety profile of the Pipeline embolization device (PED)/Pipeline Flex embolization device (PED Flex) with that of the Pipeline Flex embolization device with Shield Technology (PED Shield). After introducing the first-generation PED and the second-generation PED Flex with its updated delivery system, the PED Shield was launched with a synthetic layer of phosphorylcholine surface modification to reduce thrombogenicity. METHODS: This is a retrospective review of unruptured aneurysms treated with PED/PED Flex versus PED Shield between 2017 and 2022 at the authors' institution. Patients with ruptured aneurysms, adjunctive treatment, failed flow diverter deployment, and prior treatment of the target aneurysm were excluded. Baseline characteristics were collected for all patients, including age, sex, past medical history (hypertension, hyperlipidemia, diabetes mellitus), smoking status, aneurysm location, and aneurysm dimensions (neck, width, height) and morphology (saccular, nonsaccular). The primary outcome was procedural and periprocedural complication rates. RESULTS: The study cohort comprised 200 patients with 200 aneurysms, including 150 aneurysms treated with the PED/PED Flex and 50 treated with the PED Shield. With respect to intraprocedural and periprocedural complications, length of stay, length of follow-up, and functional outcome at discharge, there was no significant difference between the two cohorts. At the midterm follow-up, the rate of in-stent stenosis (PED/PED Flex: 14.2% vs PED Shield: 14.6%, p = 0.927), aneurysm occlusion (complete occlusion: 79.5% vs 80.5%, respectively; neck remnant: 4.7% vs 12.2%; dome remnant: 15.7% vs 7.3%; p = 0.119), and the need for retreatment (5.3% vs 0%, p = 0.097) were comparable between the two cohorts. CONCLUSIONS: This study suggests that, as compared to first- and second-generation PED and PED Flex, the third-generation PED Shield offers similar rates of complications, aneurysm occlusion, and in-stent stenosis at the midterm follow-up.

The impact of postoperative aspirin in patients undergoing Woven EndoBridge: a multicenter, institutional, propensity score-matched analysis.

BACKGROUND: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated. METHODS: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups. RESULTS: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027). CONCLUSIONS: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Artificial Intelligence and Machine Learning in the Diagnosis and Management of Stroke: A Narrative Review of United States Food and Drug Administration-Approved Technologies.

Stroke is an emergency in which delays in treatment can lead to significant loss of neurological function and be fatal. Technologies that increase the speed and accuracy of stroke diagnosis or assist in post-stroke rehabilitation can improve patient outcomes. No resource exists that comprehensively assesses artificial intelligence/machine learning (AI/ML)-enabled technologies indicated for the management of ischemic and hemorrhagic stroke. We queried a United States Food and Drug Administration (FDA) database, along with PubMed and private company websites, to identify the recent literature assessing the clinical performance of FDA-approved AI/ML-enabled technologies. The FDA has approved 22 AI/ML-enabled technologies that triage brain imaging for more immediate diagnosis or promote post-stroke neurological/functional recovery. Technologies that assist with diagnosis predominantly use convolutional neural networks to identify abnormal brain images (e.g., CT perfusion). These technologies perform comparably to neuroradiologists, improve clinical workflows (e.g., time from scan acquisition to reading), and improve patient outcomes (e.g., days spent in the neurological ICU). Two devices are indicated for post-stroke rehabilitation by leveraging neuromodulation techniques. Multiple FDA-approved technologies exist that can help clinicians better diagnose and manage stroke. This review summarizes the most up-to-date literature regarding the functionality, performance, and utility of these technologies so clinicians can make informed decisions when using them in practice.

Imaging of the Reconstructed Breast.

The incidence of breast cancer and, therefore, the need for breast reconstruction are expected to increase. The many reconstructive options available and the changing aspects of the field make this a complex area of plastic surgery, requiring knowledge and expertise. Two major types of breast reconstruction can be distinguished: breast implants and autologous flaps. Both present advantages and disadvantages. Autologous fat grafting is also commonly used. MRI is the modality of choice for evaluating breast reconstruction. Knowledge of the type of reconstruction is preferable to provide the maximum amount of pertinent information and avoid false positives. Early complications include seroma, hematoma, and infection. Late complications depend on the type of reconstruction. Implant rupture and implant capsular contracture are frequently encountered. Depending on the implant type, specific MRI signs can be depicted. In the case of myocutaneous flap, fat necrosis, fibrosis, and vascular compromise represent the most common complications. Late cancer recurrence is much less common. Rarely reported late complications include breast-implant-associated large cell anaplastic lymphoma (BIA-ALCL) and, recently described and even rarer, breast-implant-associated squamous cell carcinoma (BIA-SCC). In this review article, the various types of breast reconstruction will be presented, with emphasis on pertinent imaging findings and complications.

Proteostasis Modulation in Germline Missense von Hippel Lindau Disease.

PURPOSE: Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL. PATIENTS AND METHODS: We administered oral vorinostat to 7 subjects (ages 46.0 ± 14.5 years) and then removed symptomatic hemangioblastomas surgically (ClinicalTrials.gov identifier NCT02108002). RESULTS: Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared with untreated hemangioblastomas from same patients. We found transcriptional suppression of downstream hypoxia-inducible factor (HIF) effectors. Mechanistically, vorinostat prevented Hsp90 recruitment to mutated pVHL in vitro. The effects of vorinostat on the Hsp90-pVHL interaction, pVHL rescue, and transcriptional repression of downstream HIF effectors was independent of the location of the missense mutation on the VHL locus. We confirmed a neoplastic stromal cell-specific effect in suppression of protumorigenic pathways with single-nucleus transcriptomic profiling. CONCLUSIONS: We found that oral vorinostat treatment in patients with germline missense VHL mutations has a potent biologic effect that warrants further clinical study. These results provide biologic evidence to support the use of proteostasis modulation for the treatment of syndromic solid tumors involving protein misfolding. Proteostasis modulation with vorinostat rescues missense mutated VHL protein. Further clinical trials are needed to demonstrate tumor growth arrest.