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.

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.

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.

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.

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.

Does life history mediate discharge as a driver of multi-decadal changes in populations of freshwater fish?

Understanding how and why the size of populations varies is critical knowledge for conservation and management. While considerable work has explored how different demographic parameters affect population growth, less is known the drivers of variability in these parameters. Long-term time series tracking population size that are coupled with empirical data to examine the relative importance of different drivers are rare, especially in freshwater systems. Even rarer are studies that collect this information concurrently from multiple species with contrasting life history strategies in the same system to assess whether population size and the relative importance of drivers also vary. We studied changes in the abundance and size structure of four native freshwater fish species in the Murray River, southeastern Australia, over a continuous 19-yr period. Two species with traits typical of "equilibrium" species (Murray cod Maccullochella peelii and trout cod Maccullochella macquariensis) and two with traits of "periodic" species (golden perch Macquaria ambigua and silver perch Bidyanus bidyanus) were sampled annually and capture-mark-recapture modeling was used to ask (1) how did population size change during this period, (2) how were changes in population size related to variability in hydrology, and (3) how were changes in population size driven by different processes (local recruitment or migration events)? Populations of all four species varied throughout the study, and our results are consistent with the notion that local recruitment is an important driver of this variability for Murray cod and trout cod, whereas immigration is more important for the two other species. Increases in spring river discharge strongly influenced these responses for trout cod and golden perch. Our study provides fundamental insights into the population dynamics of these valued species, and how management strategies might differ based on their life histories. Management should focus on allowing connectivity for golden and silver perch, and on promoting local scale recruitment and survival for Murray cod and trout cod. More generally, our study highlights the importance of understanding the processes underpinning population persistence, how these processes may vary for different species, and ultimately how this knowledge can inform targeted management actions.

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency. CONCLUSIONS: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.

Plasmid mediated penicillin and tetracycline resistance among Neisseria gonorrhoeae isolates from Kenya.

BACKGROUND: Treatment of gonorrhea is complicated by the development of antimicrobial resistance in Neisseria gonorrhoeae (GC) to the antibiotics recommended for treatment. Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance in N. gonorrhoeae isolates recovered from Kenya between 2013 and 2018. METHODS: DNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembled de-novo using CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor. RESULTS: Twenty-four (66.7%) isolates had both ß-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaic penA alleles. All the isolates expressing TetM were tetracycline resistant (MIC> 1 mg/L) and had increased doxycycline MICs (up to 96 mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs. CONCLUSION: High-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borne blaTEM and tetM genes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.

Mechanical Thrombectomy in Stroke from Infective Endocarditis: Case Report and Review.

OBJECTIVE: To characterize outcomes after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) from infective endocarditis. METHODS: Case report and review of published cases. RESULTS: We report the case of a 59-year-old woman with fungal endocarditis who developed AIS from a proximal middle cerebral artery (MCA) embolus. She underwent MT, with good outcome. An additional 25 similar cases were identified from 14 publications. Among the 26 cases analyzed (mean [SD] age, 55 [18.7] years, 42% women), the MCA was the most common site of arterial occlusion. Four patients received intravenous tissue plasminogen activator treatment before MT. The median admission NIH Stroke Scale score (NIHSSS) was 15.5 [interquartile range 9.75-19.25] and the median post-procedure NIHSSS was 2 [interquartile range .75-6]. No patient developed symptomatic intracerebral hemorrhage. CONCLUSIONS: MT appears to be a safe and effective therapeutic option in infective endocarditis-related AIS with proximal-artery occlusion.

Increased population size of fish in a lowland river following restoration of structural habitat.

Most assessments of the effectiveness of river restoration are done at small spatial scales (<10 km) over short time frames (less than three years), potentially failing to capture large-scale mechanisms such as completion of life-history processes, changes to system productivity, or time lags of ecosystem responses. To test the hypothesis that populations of two species of large-bodied, piscivorous, native fishes would increase in response to large-scale structural habitat restoration (reintroduction of 4,450 pieces of coarse woody habitat into a 110-km reach of the Murray River, southeastern Australia), we collected annual catch, effort, length, and tagging data over seven years for Murray cod (Maccullochella peelii) and golden perch (Macquaria ambigua) in a restored "intervention" reach and three neighboring "control" reaches. We supplemented mark-recapture data with telemetry and angler phone-in data to assess the potentially confounding influences of movement among sampled populations, heterogeneous detection rates, and population vital rates. We applied a Bayesian hierarchical model to estimate changes in population parameters including immigration, emigration, and mortality rates. For Murray cod, we observed a threefold increase in abundance in the population within the intervention reach, while populations declined or fluctuated within the control reaches. Golden perch densities also increased twofold in the intervention reach. Our results indicate that restoring habitat heterogeneity by adding coarse woody habitats can increase the abundance of fish at a population scale in a large, lowland river. Successful restoration of poor-quality "sink" habitats for target species relies on connectivity with high-quality "source" habitats. We recommend that the analysis of restoration success across appropriately large spatial and temporal scales can help identify mechanisms and success rates of other restoration strategies such as restoring fish passage or delivering water for environmental outcomes.

Does including neck CTA in work-up of suspected intracranial hemorrhage add value?

PURPOSE: Neck CT angiography (CTA) is frequently performed in conjunction with head CTA in patients presenting with clinical signs and symptoms concerning for acute intracranial hemorrhage, despite relatively low appropriateness (ACR Appropriateness Criteria 2-6). This decision is sometimes justified by suggesting that CTA neck findings are useful in planning subsequent catheter angiography. METHODS: We investigated the value of neck CTA in patients with suspected acute intracranial hemorrhage by reviewing 220 head and neck CTAs performed in our emergency room over a 24-month period for the indication of hemorrhage or headache. Images were reviewed by two neurointerventionalists to address the value of the neck CTA for planning catheter angiography. RESULTS: Findings helpful for performing catheter angiography were observed on neck CTA in 22% (Cohen kappa 0.65), and included anatomical arch variants such as a bovine arch, direct vertebral artery arch origin, and aberrant subclavian artery. However, findings that might substantially prolong angiography for more than 10 min if unknown occurred in 5% (Cohen kappa 0.69). Incidental findings prompting additional imaging or significant clinical action occurred in 20%. Subarachnoid hemorrhage on noncontrast head CT was strongly associated with a need for subsequent angiography. CONCLUSIONS: Although CTA neck can provide helpful information for planning catheter angiography, it rarely uncovers findings that would significantly prolong the procedure if unknown. Neck CTA is therefore only recommended in patients with a confirmed intracranial hemorrhage in a pattern consistent with aneurysm or arteriovenous shunt.

Left Thalamus Arteriovenous Malformation Secondary to Radiation Therapy of Original Vermian Arteriovenous Malformation: Case Report.

A 70-year-old gentleman with history of hypothyroidism, hyperlipidemia, hypertension, and right superior cerebellar aneurysm presented to the neurosurgery service in 2008 with vertigo. Diagnostic cerebral angiography performed that year demonstrated a vermian arteriovenous malformations (AVM). The patient underwent stereotactic proton beam radiosurgery, which resulted in a decrease in flow and size of the lesion, and the patient was lost to follow-up. Now at the age of 80, the patient presented with acute gait instability. Cerebral angiogram demonstrated his stable vermian AVM and a new 1.1 cm AVM nidus in the region of the left posterior thalamus. Although AVMs are often described as congenital lesions, there is a growing body of literature suggesting that AVMs can grow, spontaneously regress, and even arise de novo in response to some insult. Understanding what leads to the growth, remodeling, regression, and hemorrhage of AVMs is crucial in order to better direct therapeutic endeavors. We would argue that this patient's AVM is secondary to endothelial cell damage from radiation therapy. Radiation can cause endothelial cell injury and upregulation of factors, such as vascular endothelial growth factor and transforming growth factor beta expression, which are implicated in AVM development pathways. We believe that this patient's new AVM is secondary to entrance radiation dosing affecting the thalamus during radiation therapy for the original vermian AVM.

CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents.

Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal manifestations (EIMs) affecting many organ systems. EIMs can occur in more than 40% of patients with IBD and are associated with significant morbidity. They occur at any time point in the course of disease, often during an active phase of bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of EIMs enables timely and more effective therapy. Physicians who image patients with IBD should be aware of the myriad extraintestinal conditions that may be detected on imaging studies, both within and outside of the abdomen, as they may predate the diagnosis of IBD. Cross-sectional imaging of unusual conditions associated with IBD will be presented, including pathology in the hepatobiliary, pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic, and pulmonary systems.

Persistent trigeminal artery aneurysm rupture inducing a carotid-cavernous fistula: its presentation and management. Illustrative case.

BACKGROUND: A carotid-cavernous fistula (CCF) is a well-recognized entity resulting from an abnormal connection between the internal carotid artery (ICA) or external carotid artery and the cavernous sinus. Typical CCF symptomology includes proptosis, chemosis, orbital bruit, headache, facial pain, and cranial nerve (CN) palsies. While CCFs most often occur posttraumatically, they can also occur spontaneously, secondary to cavernous ICA aneurysm rupture. Very rarely, they can occur secondary to the rupture of an anomalous persistent trigeminal artery (PTA) aneurysm. OBSERVATIONS: Herein, the authors describe the case of a 54-year-old woman who presented with a CN VI palsy and headache due to a CCF secondary to a PTA aneurysm rupture. The CCF was ultimately treated via coil embolization of the aneurysm and the parent PTA vessel. LESSONS: Though such occurrences are rare, clinicians should be vigilant in assessing for the presence of a PTA in patients with a CCF, as a PTA-associated CCF requires unique treatment considerations. In some cases where the PTA plays a crucial role in the posterior circulation supply, preservation of the parent vessel PTA is crucial. However, in cases in which an adequate posterior circulation collateral supply exists, embolization of the aneurysm and the parent vessel PTA is a reasonable treatment option for fistula closure. https://thejns.org/doi/10.3171/CASE24287.

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.

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.

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.