The pigeon circovirus evolution, epidemiology and interaction with the host immune system under One Loft Race rearing conditions.

This study was aimed to investigate the frequency of PiCV recombination, the kinetics of PiCV viremia and shedding and the correlation between viral replication and host immune response in young pigeons subclinically infected with various PiCV variants and kept under conditions mimicking the OLR system. Fifteen racing pigeons originating from five breeding facilities were housed together for six weeks. Blood and cloacal swab samples were collected from birds every seven days to recover complete PiCV genomes and determine PiCV genetic diversity and recombination dynamics, as well as to assess virus shedding rate, level of viremia, expression of selected genes and level of anti-PiCV antibodies. Three hundred and eighty-eight complete PiCV genomes were obtained and thirteen genotypes were distinguished. Twenty-five recombination events were detected. Recombinants emerged during the first three weeks of the experiment which was consistent with the peak level of viremia and viral shedding. A further decrease in viremia and shedding partially corresponded with IFN-γ and MX1 gene expression and antibody dynamics. Considering the role of OLR pigeon rearing system in spreading infectious agents and allowing their recombination, it would be reasonable to reflect on the relevance of pigeon racing from both an animal welfare and epidemiological perspective.

Two Lineages of Papillomaviruses Identified from Caracals (Caracal caracal) in South Africa.

Papillomaviruses (PV) infect epithelial cells and can cause hyperplastic or neoplastic lesions. In felids, most described PVs are from domestic cats (Felis catus; n = 7 types), with one type identified in each of the five wild felid species studied to date (Panthera uncia, Puma concolor, Leopardus wiedii, Panthera leo persica and Lynx rufus). PVs from domestic cats are highly diverse and are currently classified into three genera (Lambdapapillomavirus, Dyothetapapillomavirus, and Taupapillomavirus), whereas those from wild felids, although diverse, are all classified into the Lambdapapillomavirus genus. In this study, we used a metagenomic approach to identify ten novel PV genomes from rectal swabs of five deceased caracals (Caracal caracal) living in the greater Cape Town area, South Africa. These are the first PVs to be described from caracals, and represent six new PV types, i.e., Caracal caracal papillomavirus (CcarPV) 1-6. These CcarPV fall into two phylogenetically distinct genera: Lambdapapillomavirus, and Treisetapapillomavirus. Two or more PV types were identified in a single individual for three of the five caracals, and four caracals shared at least one of the same PV types with another caracal. This study broadens our understanding of wild felid PVs and provides evidence that there may be several wild felid PV lineages.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. METHODS: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. RESULTS: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). CONCLUSION: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

Characterization of humoral and cellular immunologic responses to an mRNA-based human cytomegalovirus vaccine from a phase 1 trial of healthy adults.

mRNA-1647 is an investigational mRNA-based vaccine against cytomegalovirus (CMV) that contains sequences encoding the CMV proteins glycoprotein B and pentamer. Humoral and cellular immune responses were evaluated in blood samples collected from healthy CMV-seropositive and CMV-seronegative adults who participated in a phase 1 trial of a three-dose series of mRNA-1647 (NCT03382405). Neutralizing antibody (nAb) titers against fibroblast and epithelial cell infection in sera from CMV-seronegative mRNA-1647 recipients were higher than those in sera from control CMV-seropositive samples and remained elevated up to 12 months after dose 3. nAb responses elicited by mRNA-1647 were comparable across 14 human CMV (HCMV) strains. Frequencies of antigen-specific memory B cells increased in CMV-seropositive and CMV-seronegative participants after each mRNA-1647 dose and remained elevated for up to 6 months after dose 3. mRNA-1647 elicited robust increases in frequencies and polyfunctionality of CD4+ T helper type 1 and effector CD8+ T cells in samples from CMV-seronegative and CMV-seropositive participants after stimulation with HCMV-specific peptides. The administration of three doses of mRNA-1647 to healthy adults elicited high nAb titers with wide-breadth, long-lasting memory B cells, and strong polyfunctional T-cell responses. These findings support further clinical development of the mRNA-1647 vaccine against CMV.IMPORTANCECytomegalovirus (CMV), a common virus that can infect people of all ages, may lead to serious health problems in unborn babies and those with a weakened immune system. Currently, there is no approved vaccine available to prevent CMV infection; however, the investigational messenger RNA (mRNA)-based CMV vaccine, mRNA-1647, is undergoing evaluation in clinical trials. The current analysis examined samples from a phase 1 trial of mRNA-1647 in healthy adults to better understand how the immune system reacts to vaccination. Three doses of mRNA-1647 produced a long-lasting immune response, thus supporting further investigation of the vaccine in the prevention of CMV infection.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT03382405).

Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine.

BACKGROUND: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure. METHODS: A messenger RNA (mRNA)-based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients. RESULTS: mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses. CONCLUSIONS: Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine. CLINICAL TRIALS REGISTRATION: NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59).

Assessment of Blood Loss during Neuroendovascular Procedures.

(1) Background: Neuroendovascular procedures have generally been considered to have minor or inconsequential blood loss. No study, however, has investigated this question. The purpose of this study is to quantify the blood loss associated with neuroendovascular procedures and identify predictors of blood loss, using hemoglobin change as a surrogate for blood loss. (2) Methods: A retrospective review of 200 consecutive endovascular procedures (diagnostic and therapeutic) at our institution from January 2020 to October 2020 was performed. Patients had to have pre- and post-operative hematocrit and hemoglobin levels recorded within 48 h of the procedure (with no intervening surgeries) for inclusion. (3) Results: The mean age of our cohort was 60.1 years and the male representation was 52.5%. The mean pre-operative hemoglobin/hematocrit was significantly lower among females compared to males (12.1/36.2 vs. 13.0/38.5, p = 0.003, p = 0.009). The mean hemoglobin decrease was 0.5 g/dL for diagnostic angiograms compared to 1.2 g/dL for endovascular interventions (p < 0.0001), and 1.0 g/dL for all procedures combined. In a multivariate linear regression analysis, pre-operative antiplatelet/anticoagulant use was associated with a statistically significant decrease in hemoglobin. (4) Conclusions: Our data support that blood loss from diagnostic angiograms is marginal. Blood loss in endovascular interventions, however, tends to be higher. Pre-operative blood antiplatelet/anticoagulant use and increasing age appear to increase bleeding risk and may require closer patient monitoring.

Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2.

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).

The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

OBJECTIVE: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion. METHODS: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. RESULTS: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76). CONCLUSIONS: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications.

Whole genomes of deep-sea sponge-associated bacteria exhibit high novel natural product potential.

Global antimicrobial resistance is a health crisis that can change the face of modern medicine. Exploring diverse natural habitats for bacterially-derived novel antimicrobial compounds has historically been a successful strategy. The deep-sea presents an exciting opportunity for the cultivation of taxonomically novel organisms and exploring potentially chemically novel spaces. In this study, the draft genomes of 12 bacteria previously isolated from the deep-sea sponges Phenomena carpenteri and Hertwigia sp. are investigated for the diversity of specialized secondary metabolites. In addition, early data support the production of antibacterial inhibitory substances produced from a number of these strains, including activity against clinically relevant pathogens Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Draft whole-genomes are presented of 12 deep-sea isolates, which include four potentially novel strains: Psychrobacter sp. PP-21, Streptomyces sp. DK15, Dietzia sp. PP-33, and Micrococcus sp. M4NT. Across the 12 draft genomes, 138 biosynthetic gene clusters were detected, of which over half displayed less than 50% similarity to known BGCs, suggesting that these genomes present an exciting opportunity to elucidate novel secondary metabolites. Exploring bacterial isolates belonging to the phylum Actinomycetota, Pseudomonadota, and Bacillota from understudied deep-sea sponges provided opportunities to search for new chemical diversity of interest to those working in antibiotic discovery.

Covered stent delivery in tortuous internal carotid artery for treatment of direct carotid cavernous fistula.

Direct carotid cavernous fistulas (dCCF) are high-flow shunts between the internal carotid artery (ICA) and cavernous sinus and are commonly caused by traumatic injuries. Endovascular intervention using detachable coils, with or without stenting, is often the treatment of choice; however, migration or compaction of the coils can occur due to high-flow nature of dCCFs. Alternatively, deployment of a covered stent in ICA can be considered for treatment of dCCFs. We report a case of dCCF with tortuous intracranial ICA successfully treated by placement of a covered stent graft and we will illustrate the technical aspects of the procedure. In the presence of a tortuous ICA navigation and deployment of covered stents is technically complicated and requires modified maneuvers.

Cost Comparison: Evaluating Transfemoral and Transradial Access for Diagnostic Cerebral Angiography.

BACKGROUND: Modern medicine necessitates the delivery of increasingly complex health care while minimizing cost. Transradial access (TRA) for neuroendovascular procedures is becoming more common as accumulating data demonstrate fewer complications, improved patient satisfaction, and high rates of treatment success compared with the transfemoral access (TFA) approach; however, disparities in cost between these approaches remain unclear. We compared supply and equipment costs between TRA and TFA for diagnostic cerebral angiography and evaluate the specific items that account for these differences. METHODS: We reviewed all adult patients who underwent diagnostic cerebral angiography from July 1, 2019 to December 31, 2019. Data related to patient demographics, vascular access site, catheters used, cost of catheters, arterial access sheath use, cost of sheaths, closure devices used, and cost of closure devices were collected. RESULTS: The transradial approach resulted in higher price of radial access sheath; however, the overall cost of closure devices was much lower in TRA group than in the TFA cohort. There was no significant difference in the cost of catheters. Overall, the total supply costs for TRA cerebral angiography were significantly lower than those of TFA cerebral angiography. The relative materials cost difference of using TRA was 20.9%. CONCLUSION: This study is the first itemized materials cost analysis of TRA versus TFA cerebral angiography. TRA necessitates the use of a more expensive access sheath device; however, this cost is offset by the increased cost of devices used for femoral arteriotomy closure. Overall, the supply and equipment costs were significantly lower for TRA than TFA.

Focused selection of open cerebrovascular cases for residents interested in cerebrovascular neurosurgery.

INTRODUCTION: National and international trends continue to show greater emphasis on endovascular techniques for the treatment of cerebrovascular disease. The cerebrovascular neurosurgeon however must be adequately equipped to treat these patients via both open and endovascular techniques. METHODS: The decline in open cerebrovascular cases for aneurysm clipping has forced many trainees to pursue open cerebrovascular fellowships to increase case volume. An alternative strategy has been employed at our institution, which is early identification of subspecialty focus with resident driven self-selection of open cerebrovascular cases. RESULTS: This has allowed recent graduates to obtain enfolded endovascular training and a significant number of open cerebrovascular cases in order to obtain competence and exposure. DISCUSSION: We advocate for further self-selection paradigms supplemented with simulation training in order to obviate the need for extended post-residency fellowships.

Curvularia and the Brain: Case Demonstration of Optimal Management.

Background: Curvularia is a ubiquitous fungus found in tropical climates and has been reported to grow on marijuana leaves. Rarely, it can infect humans and propagate from the nasal sinuses into the brain. Case: A 28-year-old immunocompetent patient presented with history of nasal polyps, headache, and subtle visual deficits on the right. Imaging revealed what appeared to be an invasive mass growing through the ethmoid and sphenoid sinuses into the anterior cranial fossa. Results: Otolaryngology performed an endoscopic nasal biopsy with pathology and cultures consistent for Curvularia (figure 6). A combination case with neurosurgery and otolaryngology was planned. Surgeons used a bifrontal craniotomy and endonasal approach for gross total resection. Following resection, the patient was placed on 4 weeks of amphotericin treatment followed by 12 months of voriconazole based on recommendations by infectious disease. The patient has been stable since surgery. Conclusion: Curvularia is a rare but potentially life threatening central nervous system infection that can be acquired from inhalational marijuana use. This illustrative case shows the importance of aggressive debridement followed by broad spectrum antifungal treatment to optimize outcome. With marijuana's increasing popularity, Curvalaria should be included on the differential diagnosis.

Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains.

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA. 1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 ( NCT05137236 ). One Sentence Summary: A domain-based mRNA vaccine, mRNA-1283, is immunogenic and protective against SARS-CoV-2 and emerging variants in mice.

The Evolution of Endovascular Therapy for Intracranial Aneurysms: Historical Perspective and Next Frontiers.

The history of cerebral aneurysm treatment has a rich and storied past with multiple notable luminaries contributing insights. The modern era has transitioned from primarily clip ligation to increasing use of endovascular therapy. Even more recently, the use of intrasaccular flow diverters has been introduced for the treatment of wide necked aneurysms. The field is continuing to transform, and bioactive coils and stents have resurfaced as promising adjuvants to promote aneurysm healing. Advanced imaging modalities are being developed that could further advance the endovascular arsenal and allow for porous memory polymer devices to enter the field. This focused review highlights notable historic contributions and advances to the point of futuristic technology that is actively being developed.

Clival Paraganglioma, Case Report and Literature Review.

Paragangliomas are rare tumors that may present with cranial neuropathies when located along the skull base. Supratentorial paragangliomas are less likely to secrete catecholamines but should be worked up, nonetheless. We highlight a case of a female in her fourth decade found to have a petroclival lesion following initial presentation that included one month of tooth pain, dysphagia, diplopia, hoarseness and right hemifacial hypoesthesia. Magnetic resonance imaging of the brain demonstrated a T2 hyperintense lesion favored to be a petroclival meningioma. Pre-operative angiography demonstrated a hypervascular tumor. She underwent a combined presigmoid craniotomy with posterior petrosectomy performed by both neurosurgery and neuro-otology. Pathology demonstrated paraganglioma. She had small volume residual tumor and is planned for continued outpatient radiotherapy. Paragangliomas should be on the differential for skull base lesions. Management paradigm involves multidisciplinary care and a combination of surgical resection and post-operative radiation. In this paper, we discuss underlying pathophysiology as well as appropriate workup and management.

Angiographic Pulse Wave Coherence in the Human Brain.

A stroke volume of arterial blood that arrives to the brain housed in the rigid cranium must be matched over the cardiac cycle by an equivalent volume of ejected venous blood. We hypothesize that the brain maintains this equilibrium by organizing coherent arterial and venous pulse waves. To test this hypothesis, we applied wavelet computational methods to diagnostic cerebral angiograms in four human patients, permitting the capture and analysis of cardiac frequency phenomena from fluoroscopic images acquired at faster than cardiac rate. We found that the cardiac frequency reciprocal phase of a small region of interest (ROI) in a named artery predicts venous anatomy pixel-wise and that the predicted pixels reconstitute venous bolus passage timing. Likewise, a small ROI in a named vein predicts arterial anatomy and arterial bolus passage timing. The predicted arterial and venous pixel groups maintain phase complementarity across the bolus travel. We thus establish a novel computational method to analyze vascular pulse waves from minimally invasive cerebral angiograms and provide the first direct evidence of arteriovenous coupling in the intact human brain. This phenomenon of arteriovenous coupling may be a physiologic mechanism for how the brain precisely maintains mechanical equilibrium against volume displacement and kinetic energy transfer resulting from cyclical deformations with each heartbeat. The study also paves the way to study deranged arteriovenous coupling as an underappreciated pathophysiologic disturbance in a myriad of neurological pathologies linked by mechanical disequilibrium.

Intracranial-Intracranial Bypass for Aneurysms: Quantitative Intraoperative Assessment of Flow Preservation.

BACKGROUND: Intraoperative flow measurement has proven utility in extracranial-intracranial bypass, particularly in assessing the adequacy of donors by measurement of cut flow. The nature of intracranial-intracranial (IC-IC) bypass precludes cut flow measurement, but quantitative intraoperative flow measurements may evaluate augment assessment of the bypass. OBJECTIVE: To retrospectively evaluate flow measurements performed in IC-IC bypass to determine the adequacy of the constructs in preserving flow. METHODS: With institutional review board approval, we performed a retrospective review of our bypass database from 2001 to 2021 for aneurysms treated with IC-IC bypass and with intraoperative flow measurements. Patients' preoperative characteristics, bypass indications, prebypass and postbypass intraoperative flow measurements, and patient outcomes were recorded. RESULTS: Of 346 bypasses, 21 cases using 22 IC-IC bypasses were included. The median age was 55 years; 13 of 21 cases were ruptured aneurysms. Aneurysms involved posterior inferior cerebellar artery (n = 7), middle cerebral artery (n = 6), distal anterior cerebral artery (n = 5), and anterior communicating artery (n = 3). Six bypasses were end-to-side (ETS), 10 were side-to-side (STS), and 6 were excisional with reanastomosis (end-to-end, ETE). Intraoperatively, 21 of the bypasses were patent; the postbypass/prebypass flow index averaged 1.15 (±0.32): ETE (n = 6) 1.22 ± 0.34 and ETS/STS bypasses (n = 15) 1.11 ± 0.32. All intraoperatively patent bypasses were patent on postoperative angiography. One occluded on delayed angiography without clinical sequelae. CONCLUSION: Despite advances in endovascular therapy, IC-IC bypass remains essential to the treatment of large and fusiform aneurysms. We demonstrate quantitatively that IC-IC donors provide adequate direct (ETE) and redistributed (STS ETS) flow to the recipient territory. Flow measurement provides valuable information regarding the patency and adequacy of IC-IC bypass for flow preservation.

Timing surgery and hemorrhagic complications in endocarditis with concomitant cerebral complications.

BACKGROUND: To date, limited studies have been conducted regarding the safe timing of valvular repair for infectious endocarditis (IE) in patients with radiographic findings consistent with embolic stroke or infectious intracranial aneurysm (IIA). METHODS: A single-center, retrospective review of valvular surgeries for IE was performed (2011-2019). Outcomes for patients who underwent cranial image screening and those who did not were subsequently compared. RESULTS: 276 patients underwent valvular repair for IE; 186 (67.4%) were male. The mean age was 51.0 (17.4) years. Mean time from imaging to surgery was 7.5 days. 124 (44.9%) underwent baseline cranial imaging. Of these, 22 (17.7%) had findings concerning for ischemic stroke from embolic origin. 65 patients underwent baseline diagnostic cerebral angiography. 10 (15%) of these patients harbored an IIA. Four out of these 10 (40%) underwent intervention for an IIA. Two of the four who underwent intervention (50.0%) had ruptured IIAs. The remaining six (60%) patients with IIAs received treatment with antibiotics alone. None of the patients with IIAs suffered from symptomatic hemorrhage after valvular surgery. No significant difference in symptomatic hemorrhage after valvular surgery between those with ischemic embolic stroke compared to those without (ischemic stroke-4.5% vs. no ischemic stroke-1.0%; p = 0.32). CONCLUSIONS: Patients with radiographic evidence of ischemic stroke from septic emboli can safely undergo valvular surgery for IE without increased risk of symptomatic hemorrhage. We advocate for baseline CTA screening to evaluate for IIA in patients who present with a primary diagnosis of IE and propose a management algorithm.

Understanding the genetics of intracranial aneurysms: A primer.

The genetics of intracranial aneurysms is complex. Much work has been done looking at the extracellular matrix surrounding cerebral vasculature as well as the role of matrix metalloproteinases. This comprehensive review summarizes what is known to date about the important genetic components that predispose to aneurysm formation and critically discusses the published findings. We discuss promising pre-clinical models of aneurysm formation and subarachnoid hemorrhage, and highlight avenues for future discovery, while considering limitations in the research to date. This review will further serve as a comprehensive reference guide to understand the genetic underpinnings for aneurysm pathophysiology and act as a primer for further investigation.