Faculty Bibliography

BACKGROUND:Anatomical variants of the anterior cerebral artery (ACA) may increase technical complexity during endovascular treatment of distal ACA aneurysms (DACA). However, their impact on treatment outcomes remains unclear. This study evaluated whether ACA variants influence angiographic and clinical outcomes following endovascular treatment. METHODS:A retrospective multicenter analysis was conducted using data from the CRETA Registry, including patients with ruptured and unruptured DACA treated endovascularly. Patients were grouped according to ACA anatomy (variant vs. conventional). Outcomes were compared after propensity score matching (PSM) to adjust for confounders including age, aneurysm rupture status, dome-to-neck ratio, branch origin, and treatment type. The primary outcome was aneurysm occlusion at last follow-up based on the Raymond-Roy classification. Secondary outcomes included ischemic and hemorrhagic complications, vasospasm, and clinical outcome measured by the modified Rankin Scale (mRS). RESULTS:After PSM, 128 patients were included (64 per group). Among patients with available imaging follow-up (54 in the conventional group and 55 in the variant group), adequate occlusion rates were comparable between the variant and conventional ACA groups (81.5% vs. 85.5%; p = 0.600). No significant differences were observed in ischemic or hemorrhagic complications, vasospasm, or long-term clinical outcomes. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS:ACA anatomical variants do not adversely affect the safety or efficacy of endovascular treatment for DACA. With appropriate anatomical assessment and treatment selection, endovascular therapy remains effective even in the presence of complex ACA configurations.

The September 11, 2001, terrorist attacks on the World Trade Center (9/11) exposed both disaster responders and community members to a complex mixture of environmental contaminants, resulting in long-term health consequences. While clinical and research efforts have characterized health effects among adult survivors (community members) and responders, less is known about individuals who were exposed in utero, during childhood, adolescence, or young adulthood. Recognizing this gap, Congress amended the Public Health Service Act (42 U.S.C. § 300mm-51(c)) to establish a Research Cohort for Emerging Health Impacts on Youth to promote research on those individuals who were 21 years of age or younger at the time of exposure. This Commentary reviews the historical development of post-9/11 monitoring, treatment, and research programs, and discusses the unique challenges of conducting research in such a youth cohort 25 years after the event. A central coordinating center supported by community-based field sites offers a promising approach to promoting research among this cohort and addressing critical gaps in understanding the lifelong impacts of 9/11 exposures.

BACKGROUND:Patients with diabetes frequently have multivessel disease and are at increased risk of adverse outcomes. The outcomes with a new-generation ultra-thin strut sirolimus-eluting stent (SES) vs everolimus-eluting stent (EES) is unclear as stent-to-stent comparison trials have routinely excluded these patients or included a small proportion of such patients. OBJECTIVES/OBJECTIVE:The purpose of this study was to compare the clinical outcomes of ultra-thin biodegradable polymer (BP) SES vs durable polymer (DP) EES when combined with contemporary optimal medical therapy in patients with diabetes and multivessel disease. METHODS:The TUXEDO-2 is an investigator-initiated prospective, open-label, multicenter, 2 × 2 factorial, randomized (1:1) controlled trial. Patients undergoing percutaneous coronary intervention were randomized to receive either a Supraflex Cruz SES or Xience EES. The participants were also randomized to Ticagrelor or Prasugrel. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction or ischemia-driven target lesion revascularization at 1-year follow up. The trial was designed to test noninferiority of BP-SES vs DP-EES, with a noninferiority margin of 4.5% (1-sided upper 97.5% confidence bound). RESULTS:= 0.005). There were no significant differences in cardiac death (3.6% vs 3.4%), target vessel myocardial infarction (6.61% vs 7.54%), and ischemia-driven target lesion revascularization (0.8% vs 1.0%) between the 2 groups. Nonfatal myocardial infarction (4.7% vs 6.4%) and stent thrombosis was similar (1.0 % vs 0.7%) between the 2 groups. CONCLUSIONS:In patients with diabetes and multivessel disease undergoing percutaneous coronary intervention, ultra-thin biodegradable polymer SES was noninferior to durable polymer EES at 1 year follow-up. (Trial Registration Number CTRI/2019/11/022088).

The Orthobunyavirus genus of arthropod-borne segmented RNA viruses comprises important pathogens including the human-infecting Oropouche virus and ruminant-infecting Schmallenberg virus (SBV). The prototypical Bunyamwera orthobunyavirus (BUNV) possesses envelope-embedded glycoprotein Gn-Gc tripodal spikes, of which the ectodomains mediate virus entry, while endodomains interact with nucleoprotein (NP) enwrapped genome segments driving virion assembly. Interestingly, BUNV Gc head/stalk domains are redundant for virus growth in mammalian cells, consistent with isolations of SBV from ruminants bearing head/stalk deletions. However, these domains appear strictly maintained in orthobunyavirus isolations from arthropods in nature. To investigate the molecular mechanism that underlines this discrepancy, we compared the multiplication characteristics of wildtype BUNV (BUNV-WT) with a Gc head/stalk deleted BUNV (BUNV-∆7). In mammalian cells BUNV-WT and BUNV-∆7 grew to equivalent titres, whereas in insect cells BUNV-∆7 titres were 1000-fold lower and strikingly produced no virions following blood meal infection of Aedes mosquitoes. To understand this insect-specific restriction in virion production, we showed the intracellular abundance of BUNV-WT and BUNV-∆7 Gc and NP components were equivalent, suggesting the deletion impacted post-translational stages of the infection cycle. To explore this, we investigated Gc and ∆7-Gc interactions during BUNV-WT and BUNV-∆7 infections of both insect and mammalian cells by co-immunoprecipitation and multiplex mass spectrometry, revealing ∆7-Gc exhibited markedly reduced NP interactions in insect cells, potentially indicating reduced segment interactions during assembly. We hypothesise that the Gc head/stalk performs an insect cell-specific role in segment recruitment during virion formation, and that maintenance in nature of full-length Gc is due to this essential role in the insect host.

PURPOSE/UNASSIGNED:Vesicourethral anastomotic stenosis (VUAS) occurs after 1 to 3% of robotic-assisted radical prostatectomies (RARPs). Pelvic fascia-sparing techniques preserve more native anatomy and may reduce stenoses, but evidence is lacking. The aim of this study was to compare stenosis incidence, management, and outcomes after standard vs pelvic fascia-sparing RARP. MATERIALS AND METHODS/UNASSIGNED:We conducted a multi-institutional retrospective study of 910 standard, 409 Retzius-sparing, and 272 hood RARP during February 2012-September 2025. Standard and hood techniques used 18Fr urethral catheters, and the Retzius-sparing technique used 18Fr suprapubic catheters. The primary end point was cystoscopically confirmed VUAS requiring intervention within 12 months. Urinary continence was assessed using the validated Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Multivariable logistic regression assessed factors associated with VUAS. RESULTS/UNASSIGNED:= .046). CONCLUSIONS/UNASSIGNED:There were no VUAS after Retzius-sparing RARP, and Retzius-sparing vs standard approach was associated with lower odds of stenosis. Endoscopic management with structured self-catheterization achieved high success without worsening incontinence. Prospective studies are needed to validate our findings.

INTRODUCTION AND PROBLEM STATEMENT/UNASSIGNED:Competency in brain death/death by neurologic criteria (BD/DNC) determination is an Accreditation Council for Graduate Medical Education (ACGME) milestone in neurology residency and neurocritical care fellowship; however, trainees have limited clinical exposure and receive inconsistent training across institutions. Simulation offers a standardized, safe environment to teach and assess BD/DNC, but multi-institutional implementation remains unstudied. The aim of this study was to evaluate the feasibility of implementing a consensus-based BD/DNC curriculum and to assess its impact on trainee confidence. LEARNING OBJECTIVES/UNASSIGNED:By the end of the curriculum, trainees will be confident in assessing BD/DNC prerequisites, performing a complete neurologic examination, safely conducting and interpreting apnea testing, and accurately declaring BD/DNC. METHODS AND CURRICULUM DESCRIPTION/UNASSIGNED:test. RESULTS/UNASSIGNED:Nineteen participants (9 female [47%]; predominantly PGY-4 trainees) were enrolled. Median [IQR] pre-post composite confidence scores improved significantly across all domains: "Setup and Family Counseling," 4 [3.5-4] to 4.5 [4-5]; "Prerequisites," 4 [4-5] to 4.5 [4-5]; "Neurologic Examination," 4 [4-4] to 4.5 [4-5]; and "Apnea Test and Declaration of BD/DNC," 3 [3-4] to 5 [4-5]. The effect sizes (Wilcoxon r) ranged from 0.79 to 0.88 across domains. There were no significant differences in the magnitude of improvement between high-fidelity and low-fidelity groups. After curriculum implementation, 13 of 19 participants (68%) self-assessed their ACGME BD/DNC milestone competency to be level 4 or 5. DISCUSSION AND LESSONS LEARNED/UNASSIGNED:This multi-institutional pilot demonstrated that a consensus-based BD/DNC simulation curriculum is feasible and improves trainee confidence despite limited previous clinical exposure. Key lessons include the feasibility of multicenter collaboration, standardizing core practices while accommodating local variability, and designing adaptable curricula that achieve similar outcomes across resource-diverse settings.

OBJECTIVE:To report updated patient-reported (PRO) health-related quality of life (HRQOL) findings and evaluate the effect of disease progression on HRQOL using data from the final analysis of the PRIMA/ENGOT-OV26/GOG-3012 trial. METHODS:Patients were randomized 2:1 to niraparib first-line maintenance or placebo. Longitudinal HRQOL was a prespecified secondary endpoint assessed via European Organisation for Research and Treatment of Cancer QOL-Core Questionnaire (EORTC QLQ-C30) and -Ovarian Cancer module (EORTC QLQ-OV28), Functional Assessment of Cancer Therapy Ovarian Cancer Symptom Index (FOSI), and EuroQol 5-dimension 5-level questionnaire with visual analog scale (EQ-VAS). Post hoc analyses evaluated least-squares mean change from baseline or last on-treatment visit before disease progression (clinical cutoff: April 8, 2024). RESULTS:Questionnaire completion rates exceeded 89% through cycle 24 and were 80% at end of treatment. Early differences in gastrointestinal symptom scores between arms resolved over time, and no differences in overall HRQOL were observed. Disease progression reduced overall HRQOL across arms, with marked reductions in EORTC QLQ-C30 overall HRQOL, FOSI, and EQ-VAS scores that never recovered to pre-progression levels. Progression also resulted in sustained deterioration across all EORTC QLQ-C30 and QLQ-OV28 functional scales and worsening symptom scores, particularly for fatigue, dyspnea, pain, and appetite loss. Similar results were observed when patients were evaluated by homologous recombination deficiency status. CONCLUSION/CONCLUSIONS:In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT02655016.

BACKGROUND:Fetal and neonatal outcomes and factors increasing mortality risk in fetal truncus arteriosus are not well characterized. We aimed to examine the prenatally encountered cardiac spectrum, define extracardiac and genetic associations, explore clinical outcomes and identify prenatal factors associated with worse outcomes in a contemporary large cohort. METHODS:A multicenter retrospective cohort study was conducted via the Fetal Heart Society Research Collaborative including fetal truncus arteriosus cases encountered between January 1, 2010, and September 1, 2021, within 22 North American cardiac centers. Demographic, clinical, anatomic, and functional fetal echocardiographic variables were analyzed for associations with presurgical death (fetal death/neonatal presurgical death/neonatal listing for heart transplantation before initial hospital discharge). Variables were compared between survivors and nonsurvivors with nonparametric tests and univariable logistic regression; a multivariable linear probability model was used for further assessment after adjusting for confounders. RESULTS:Of 378 fetuses diagnosed prenatally, 201 (53.2%) had a genetic abnormality or extracardiac anomaly identified. Pregnancy termination was chosen in 47 (12.4%) pregnancies and palliative care in 13 (3.4%). Of 318 pregnancies with intention to treat, 17 (5.3%) ended in fetal death and 19 (6%) in neonatal presurgical death. In addition to prematurity and low birth weight, truncal valve stenosis (but not regurgitation or anatomic subtype) and ventricular dysfunction were associated with presurgical death. CONCLUSIONS:Half of fetuses with truncus arteriosus will have an associated genetic abnormality or extracardiac anomaly. Truncal valve stenosis and ventricular dysfunction, as well as preterm birth and low birth weight, are associated with presurgical death. These data are important for prognostication and prenatal counseling.