Vessel Wall Imaging in Angiogram-Negative Diffuse Subarachnoid Hemorrhage Reveals a Ruptured Lenticulostriate Aneurysm.

A patient presented with acute onset headache and subsequent unconsciousness. The neurologic exam showed left-sided myoclonic jerking and right flaccid hemiparalysis. Noncontrast computed tomography revealed diffuse subarachnoid hemorrhage (SAH) with acute hydrocephalus. Initial digital subtraction angiography (DSA) showed no culprit source for SAH. Repeat DSA on day 7 after initial presentation raised suspicion for left internal carotid artery ophthalmic segment and left lateral lenticulostriate artery (LSA) aneurysms. A magnetic resonance vessel wall imaging (VWI) exam was performed given the presence of multiple potential culprit aneurysms. Vessel wall enhancement around the dome of the left LSA aneurysm suggested rupture, which then facilitated treatment with surgical clipping. LSA aneurysms are exceedingly rare and challenging to treat. Given the associated high degree of morbidity, expedient diagnosis is critical to direct management. VWI could be a valuable tool for detecting ruptured aneurysms in the setting of angiogram-negative SAH.

Aging as a target for the prevention and treatment of Alzheimer's disease.

Alzheimer's disease (AD), the most common etiology of dementia in older adults, is projected to double in prevalence over the next few decades. Current treatments for AD manage symptoms or slow progressive decline, but are accompanied by significant inconvenience, risk, and cost. Thus, a better understanding of the risk factors and pathophysiology of AD is needed to develop novel prevention and treatment strategies. Aging is the most important risk factor for AD. Elucidating molecular mechanisms of aging may suggest novel therapeutic targets. While aging is inevitable, it may be accelerated by caloric excess and slowed by caloric restriction (CR) or intermittent fasting. As such, CR may slow aging and reduce the risk of all diseases of aging, including dementia due to AD. The literature on CR, intermittent fasting, and treatment with polyphenols such as resveratrol-a pharmacologic CR-mimetic-supports this hypothesis based on clinical outcomes as well as biomarkers of aging and AD. More studies exploring the role of CR in regulating aging and AD progression in man are needed to fill gaps in our understanding and develop safer and more effective strategies for the prevention and treatment of AD.

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.

A revisited history of cacao domestication in pre-Columbian times revealed by archaeogenomic approaches.

Humans have a long history of transporting and trading plants, contributing to the evolution of domesticated plants. Theobroma cacao originated in the Neotropics from South America. However, little is known about its domestication and use in these regions. In this study, ceramic residues from a large sample of pre-Columbian cultures from South and Central America were analyzed using archaeogenomic and biochemical approaches. Here we show, for the first time, the widespread use of cacao in South America out of its native Amazonian area of origin, extending back 5000 years, likely supported by cultural interactions between the Amazon and the Pacific coast. We observed that strong genetic mixing between geographically distant cacao populations occurred as early as the middle Holocene, in South America, driven by humans, favoring the adaptation of T. cacao to new environments. This complex history of cacao domestication is the basis of today's cacao tree populations and its knowledge can help us better manage their genetic resources.

Amyloid and tau-PET in early-onset AD: Baseline data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

INTRODUCTION: We aimed to describe baseline amyloid-beta (Aß) and tau-positron emission tomograrphy (PET) from Longitudinal Early-onset Alzheimer's Disease Study (LEADS), a prospective multi-site observational study of sporadic early-onset Alzheimer's disease (EOAD). METHODS: We analyzed baseline [18F]Florbetaben (Aß) and [18F]Flortaucipir (tau)-PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aß+) from EOnonAD (Aß-) based on the combination of visual read by expert reader and image quantification. RESULTS: 243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid-PET; 231 (95.1%) of them were tau-PET positive (A+T+). Tau-PET signal was elevated across cortical regions with a parietal-predominant pattern, and higher burden was observed in younger and female EOAD participants. DISCUSSION: LEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau-PET binding at baseline might have implications for therapeutic strategies in patients with EOAD. HIGHLIGHTS: 72% of patients with clinical EOAD were positive on both amyloid- and tau-PET. Amyloid-positive patients with EOAD had high tau-PET signal across cortical regions. In EOAD, tau-PET mediated the relationship between amyloid-PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau-PET.

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.

Learning slopes in early-onset Alzheimer's disease.

OBJECTIVE: Investigation of learning slopes in early-onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early-onset dementia with and without ß-amyloid positivity METHOD: Data from 310 participants in the Longitudinal Early-Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determined RESULTS: Worse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric-the learning ratio (LR)-outperformed other learning slope calculations across analyses CONCLUSIONS: Learning slopes appear to be sensitive to early-onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses. HIGHLIGHTS: Learning is impaired in amyloid-positive EOAD, beyond cognitive severity scores alone. Amyloid-positive EOAD participants perform worse on learning slopes than amyloid-negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection.

OBJECTIVE: The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point. METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer's disease [EOnonAD; n = 70]). RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures. CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant. HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

Covered stent delivery in tortuous internal carotid artery for treatment of direct carotid cavernous fistula / Colocación de un stent cubierto en una arteria carótida interna tortuosa para el tratamiento de la fístula carótida cavernosa directa

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 (AU)

Las fístulas carótidas cavernosas directas (dCCF) son derivaciones de alto flujo entre la arteria carótida interna (ACI) y el seno cavernoso y suelen ser causadas por lesiones traumáticas. La intervención intravascular con espirales desmontables, con o sin stent, suele ser el tratamiento de elección; sin embargo, la migración o compactación de las bobinas puede ocurrir debido a la naturaleza de alto flujo de los dCCF. Alternativamente, se puede considerar el despliegue de un stent cubierto en la ACI para el tratamiento de dCCF. Presentamos un caso de dCCF con ACI intracraneal tortuosa tratada con éxito mediante la colocación de una endoprótesis cubierta e ilustraremos los aspectos técnicos del procedimiento. En presencia de una ACI tortuosa, la navegación y el despliegue de los stents cubiertos es técnicamente complicado y requiere maniobras modificadas (AU)

Derivation and Internal Validation of a Risk Score for Predicting Chlamydia trachomatis Infection in Kenyan Women Planning Conception.

BACKGROUND: Availability of laboratory confirmation of sexually transmitted infections is increasing in low- and middle-income countries, but costs continue to limit their access. Chlamydia trachomatis (CT) is a sexually transmitted infection of significant clinical importance, particularly among women. This study aimed to develop a risk score to identify women with a higher likelihood of CT infection, who could then be prioritized for laboratory testing, in a population of Kenyan women planning pregnancies. METHODS: Women with fertility intentions were included in this cross-sectional analysis. Logistic regression was used to estimate odds ratios for the association between demographic, medical, reproductive, and behavioral characteristics and the prevalence of CT infection. A risk score was developed and validated internally based on the regression coefficients in the final multivariable model. RESULTS: The prevalence of CT was 7.4% (51 of 691). A risk score for predicting CT infection, with scores 0 to 6, was derived from participants' age, alcohol use, and presence of bacterial vaginosis. The prediction model yielded an area under the receiver operating curve of 0.78 (95% confidene interval [Cl], 0.72-0.84). A cutoff of ≤2 versus >2 identified 31.8% of women as higher risk with moderate sensitivity (70.6%; 95% Cl, 56.2-71.3) and specificity (71.3%; 95% Cl, 67.7-74.5). The bootstrap-corrected area under the receiver operating curve was 0.77 (95% Cl, 0.72-0.83). CONCLUSIONS: In similar populations of women planning pregnancies, this type of risk score could be useful for prioritizing women for laboratory testing and would capture most women with CT infections while performing more costly testing in less than half of the population.

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.

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results.

Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population.

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.

Corrigendum: A 5-min Cognitive Task With Deep Learning Accurately Detects Early Alzheimer's Disease.

[This corrects the article DOI: 10.3389/fnagi.2020.603179.].

Associations Between Vaginal Bacteria and Bacterial Vaginosis Signs and Symptoms: A Comparative Study of Kenyan and American Women.

Background: Bacterial colonization and associations with bacterial vaginosis (BV) signs and symptoms (Amsel criteria) may vary between populations. We assessed relationships between vaginal bacteria and Amsel criteria among two populations. Methods: Kenyan participants from the placebo arm of the Preventing Vaginal Infections (PVI) trial and participants from a Seattle-based cross-sectional BV study were included. Amsel criteria were recorded at study visits, and the vaginal microbiota was characterized using 16S rRNA gene sequencing. Logistic regression models, accounting for repeat visits as appropriate, were fit to evaluate associations between bacterial relative abundance and each Amsel criterion. Results: Among 84 PVI participants (496 observations) and 220 Seattle participants, the prevalence of amine odor was 25% and 40%, clue cells 16% and 37%, vaginal discharge 10% and 52%, elevated vaginal pH 69% and 67%, and BV 13% and 44%, respectively. BV-associated bacterium 1 (BVAB1) was positively associated with all Amsel criteria in both populations. Eggerthella type 1, Fannyhessea (Atopobium) vaginae, Gardnerella spp., Sneathia amnii, and Sneathia sanguinegens were positively associated with all Amsel criteria in the Seattle study, and all but discharge in the PVI trial. Conclusions: Core vaginal bacteria are consistently associated with BV signs and symptoms across two distinct populations of women.

Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV.

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve.

Geographic Variation in HIV Testing Among Transgender and Nonbinary Adults in the United States.

BACKGROUND: Transgender and nonbinary (TNB) populations are disproportionately affected by HIV and few local health departments or HIV surveillance systems collect/report data on TNB identities. Our objective was to estimate the prevalence of HIV testing among TNB adults by US county and state, with a focus on the Ending the HIV Epidemic (EHE) geographies. METHODS: We applied a Bayesian hierarchical spatial small area estimation model to data from the 2015 US Transgender Survey, a large national cross-sectional Internet-based survey. We estimated the county- and state-level proportion of TNB adults who ever tested or tested for HIV in the last year by gender identity, race/ethnicity, and age. RESULTS: Our analysis included 26,100 TNB participants with valid zip codes who resided in 1688 counties (54% of all 3141 counties that cover 92% of the US population). The median county-level proportion of TNB adults who ever tested for HIV was 44% (range 10%-80%) and who tested in the last year was 17% (range 4%-44%). Within most counties, testing was highest among transgender women, black respondents, and people aged ≥25 years. HIV testing was lowest among nonbinary people and young adults aged <25 years. The proportion of TNB adults who tested within the last year was very low in most EHE counties and in all 7 rural states. CONCLUSIONS: HIV testing among TNB adults is likely below national recommendations in the majority of EHE geographies. Geographic variation in HIV testing patterns among TNB adults indicates that testing strategies need to be tailored to local settings.

Determinants of intracranial aneurysm retreatment following embolization with a single flow-diverting stent.

PURPOSE: Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion. METHODS: A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months' clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment. RESULTS: We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter ≥10 mm (p = 0.012), pre-clinoid internal carotid artery location (p = 0.012), distal > proximal parent vessel diameter (p = 0.042), and later dual antiplatelet therapy (DAPT) discontinuation (p < 0.001) were predictive of retreatment. Multivariate analysis identified discontinuation of DAPT >12 months (p = 0.003) as a strong determinant of retreatment with dome diameter ≥10 mm trending toward statistical significance (p = 0.064). Large aneurysm neck diameter, presence of aneurysm branch vessels, patient age, smoking history, and hypertension were not determinant of retreatment on multivariate analysis. CONCLUSIONS: Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

Current Clinical Applications of Intracranial Vessel Wall MR Imaging.

Intracranial vessel wall MR imaging (VWI) is increasingly being used as a valuable adjunct to conventional angiographic imaging techniques. This article will provide an updated review on intracranial VWI protocols and image interpretation. We review VWI technical considerations, describe common VWI imaging features of different intracranial vasculopathies and show illustrative cases. We review the role of VWI for differentiating among steno-occlusive vasculopathies, such as intracranial atherosclerotic plaque, dissections and Moyamoya disease. We also highlight how VWI may be used for the diagnostic work-up and surveillance of patients with vasculitis of the central nervous system and cerebral aneurysms.