Citations

Background Animal models are essential for evaluating endovascular device safety and efficacy. Rats offer advantages, such as genetic manipulability, lower cost, and shorter healing and breeding cycles, compared to large animals. These features support studying aneurysm healing mechanisms and enable high-throughput testing. We developed an optimal rat aneurysm model for device evaluation. Methods Saccular aneurysms were created at the origins of the left renal artery (LRA) with acetylsalicylic acid (ASA) (LRA/ASA group, n = 7); the right common iliac artery (RCIA) with ASA alone (RCIA/ASA group, n = 6) or ASA plus clopidogrel (CLP) (RCIA/ASA + CLP group, n = 7); and the left common iliac artery (LCIA) with ASA + CLP (LCIA/ASA + CLP group, n = 7). The origins of these arteries were surgically exposed. During temporary ligation of the vessel origin, the vessel was bisected and endoluminal elastase was incubated in the proximal stump for 10 min, followed by release of the proximal ligation and permanent ligation of the stump. Angiographical and histological analysis were performed 4 weeks post-procedure. Results Follow-up digital subtraction angiography revealed mean ± standard deviation aneurysm height/neck dimensions of 1.2 ± 0.4/1.2 ± 0.1, 2.9/3.1, 2.3 ± 0.6/1.9 ± 0.3, and 2.1 ± 0.6/2.0 ± 0.4 mm for the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. The survival rate was 29%, 17%, 71%, and 86% in the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. Histopathological analysis of these aneurysms confirmed the absence of the internal elastic lamina and revealed aneurysmal changes in the arterial wall, resembling the pathological findings observed in human aneurysm specimens. Conclusions Common iliac aneurysm models with ASA + CLP can be used to evaluate the safety and efficacy of endovascular devices.

Importance The potential utility of real-time digital therapeutics that identify impending behavioral outbursts to proactively apply evidence-based interventions for managing children with disruptive behavior disorder has not been tested. Objectives To evaluate feasibility and adherence of a digitally augmented, real-time, proactive behavioral intervention (smartwatch) for children with disruptive behaviors. Design, Setting, and Participants This randomized clinical trial was conducted between March 1, 2022, and December 31, 2023, at Mayo Clinic in Rochester, Minnesota. The study enrolled children aged 3 to 7 years with externalizing behavior problems rated above the clinically significant range (I score ≥120; T score ≥60) on the Eyberg Child Behavior Inventory (ECBI). Interventions Twelve weekly sessions of parent-child interaction therapy (PCIT) (treatment as usual [TAU] arm) vs artificial intelligence (AI)–enhanced PCIT augmented with real-time behavioral outburst alerts (PCIT-AI arm). Main Outcomes and Measures The primary outcome was achieving the a priori feasibility benchmark set at greater than 70% for both completion of PCIT sessions and daily smartwatch wear. Parental reaction time to behavior prompts was measured in seconds. Secondary outcomes were percentage changes in ECBI and Pediatric Sleep Questionnaire scores. Behavioral outburst duration was examined based on parental logs of start and end times of observed tantrums using a smartphone application. Result This study enrolled 50 children (median [IQR] age, 5.0 [4.0-6.0] years; 34 [68%] male and 16 [32%] female; 28 randomized to the PCIT-AI arm and 22 to the PCIT-TAU arm). Of these children, 37 (74%; 21 in the PCIT-AI arm and 16 in the PCIT-TAU arm) completed PCIT, with children wearing the watch a median (IQR) 75.7% (67.8%-82.9%) of the time, thus achieving the feasibility benchmark (primary outcome). Median (IQR) response time to behavior prompts in the PCIT-AI arm was 3.65 (2.07-7.08) seconds. Assessing between-group differences, there was no statistically significantly greater numerical improvement in ECBI-intensity percentage change (13.86%; 95% CI, −1.41% to 29.14%), ECBI-problem percentage change subscale scores (38.59%; 95% CI, −1.22% to 78.40%), or absolute change in Pediatric Sleep Questionnaire scores (−0.16; 95% CI, −1.85 to 1.53) with the PCIT-AI arm than with the PCIT-TAU arm. Children in the PCIT-AI arm had significantly shorter mean (SD) tantrum durations (10.4 [20.8] minutes vs 22.1 [30.0] minutes; P < .001) and lower odds of tantrums lasting for 15 minutes or more (odds ratio, 3.66; 95% CI, 2.72-4.95). Conclusions and Relevance In this randomized clinical trial, both recruitment and technology feasibility benchmarks were achieved. The findings inform the design of fully powered efficacy study of wearable, digitally augmented PCIT for children with disruptive behaviors. Trial Registration ClinicalTrials.gov Identifier: NCT05077722

Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

Human Epilepsy Project (1) Investigators. Treatment Response to Antiseizure Medications in People With Newly Diagnosed Focal Epilepsy Barnard SN, Chen Z, Holmes M, Kanner AM, Hegde M, Kuzniecky R, Lowenstein D, French JA. JAMA Neurol . 2025 Aug 25:e252949. doi: 10.1001/jamaneurol.2025.2949. Epub ahead of print. PMID: 40853673 Importance: Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. Objective: To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. Design, setting, and participants: The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. Exposure: ASM (variable). Main outcomes and measures: The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). Results: Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21–44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33–3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7–16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8–3.2) than those who did (median, 7.4 months; 95% CI, 4.0–10.7). Those with infrequent pretreatment seizures were 0.30-fold less likely to be treatment resistant than those with very frequent seizures (hazard ratio, 0.30; 95% CI, 0.14–0.64; P = .002; Holm–Bonferroni-corrected P = .006). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (relative risk, 1.78; 95% CI, 1.26–2.52; P = .001). Conclusions and relevance: In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor.

Carotid blowout is the rupture of a carotid artery or branch vessel, a dangerous complication in post-treatment head and neck cancer patients. The purpose of this retrospective case review is to identify imaging features suggestive of eminent carotid blowout on routine surveillance post-treatment neck imaging, so that a prompt neuroendovascular consult is obtained and the patient is preemptively treated, thus improving patient outcomes. It is important to carefully interrogate the carotid vessels with appropriate window/leveling for irregularity, adjacent tissue ulceration, exposed vessel to either air or fluid, surrounding tumor, and pseudoaneurysm.

ABSTRACT Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, accounting for 90%–95% of all thyroid cancers worldwide. For many years, treatment options for patients with locally advanced or metastatic radioiodine refractory disease were limited. Advances in understanding oncogenic and angiogenic signaling pathways, such as vascular endothelial growth factor receptors, fibroblast growth factor receptors, platelet derived growth factor receptor, rearranged during transfection ( RET) , and BRAF have led to the development of targeted therapies that have transformed management over the past two decades. Multikinase inhibitors such as lenvatinib, sorafenib, vandetanib, and cabozantinib have demonstrated clinical efficacy in randomized clinical trials. Most recently, mutation-specific kinase inhibitors such as selpercatinib for RET -fusion positive cancers, and the combination of dabrafenib with trametinib for BRAF V600E -mutant disease, have been approved and further expanded treatment options for these patients. In this review, we summarize the current evidence on Food and Drug Administration-approved targeted therapies for metastatic thyroid cancer and discuss their clinical impact.

Background: Carriers of a pathogenic variant (PV) in BRCA1 face a high risk of breast cancer. This study estimated the risk of developing breast cancer according to mutation type and location. Methods: BRCA1 carriers with no personal history of breast cancer or bilateral mastectomy were included. Detailed information on clinical and family history was collected by questionnaire. Survival analysis was used to estimate 15-year cumulative risk according to PV type and location. Results: A total of 3677 BRCA1 carriers were followed for a mean of 7.2 years (range 0.1–15.0 years); 481 incident breast cancers were documented. Overall, the 15-year cumulative incidence was 25%. Risk estimates varied by exon, ranging from 9% (exon 21) to 19% (exon 12) to 36% (exon 15); however, strata were small. Carriers of four founder mutations common in Eastern Europe (c.5263_5264insC, c.181T > G, c.66_67delAG and c.4034delA) experienced a lower-than-expected cancer risk (15.9–24.4%) compared to other PVs (28.8%) (p = 0.02). Conclusions: Although our data suggests some variability in penetrance based on specific BRCA1 PV, this was based on a large number of founder mutations. Breast cancer management strategies should continue to be based on comprehensive risk assessment.