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Petechial hemorrhage in mechanical thrombectomy for distal and medium-vessel occlusions: technical considerations and outcomes
No full textObjective: Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications.
Methods: A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported.
Results: Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21-2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01-1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15-2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40-0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69-0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39-0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36-0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44-0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23-2.76; p < 0.001).
Conclusions: PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.No embarg
Testing a Machine Learning-Based Adaptive Motivational System for Socioeconomically Disadvantaged Smokers (Adapt2Quit): Protocol for a Randomized Controlled Trial
Full text linkBackground: Individuals who are socioeconomically disadvantaged have high smoking rates and face barriers to participating in smoking cessation interventions. Computer-tailored health communication, which is focused on finding the most relevant messages for an individual, has been shown to promote behavior change. We developed a machine learning approach (the Adapt2Quit recommender system), and our pilot work demonstrated the potential to increase message relevance and smoking cessation effectiveness among individuals who are socioeconomically disadvantaged.
Objective: This study protocol describes our randomized controlled trial to test whether the Adapt2Quit recommender system will increase smoking cessation among individuals from socioeconomically disadvantaged backgrounds who smoke.
Methods: Individuals from socioeconomically disadvantaged backgrounds who smoke were identified based on insurance tied to low income or from clinical settings (eg, community health centers) that provide care for low-income patients. They received text messages from the Adapt2Quit recommender system for 6 months. Participants received daily text messages for the first 30 days and every 14 days until the end of the study. Intervention participants also received biweekly texting facilitation messages, that is, text messages asking participants to respond (yes or no) if they were interested in being referred to the quitline. Interested participants were then actively referred to the quitline by study staff. Intervention participants also received biweekly text messages assessing their current smoking status. Control participants did not receive the recommender messages but received the biweekly texting facilitation and smoking status assessment messages. Our primary outcome is the 7-day point-prevalence smoking cessation at 6 months, verified by carbon monoxide testing. We will use an inverse probability weighting approach to test our primary outcome. This involves using a logistic regression model to predict nonmissingness, calculating the inverse probability of nonmissingness, and using it as a weight in a logistic regression model to compare cessation rates between the two groups.
Results: The Adapt2Quit study was funded in April 2020 and is still ongoing. We have completed the recruitment of individuals (N=757 participants). The 6-month follow-up of all participants was completed in November 2024. The sample consists of 64% (486/757) female participants, 35% (265/757) Black or African American individuals, 51.1% (387/757) White individuals, and 16% (121/757) Hispanic or Latino individuals. In total, 52.6% (398/757) of participants reported having a high school education or being a high school graduate; 70% (529/757) smoked their first cigarette within 30 minutes of waking, and half (379/757, 50%) had stopped smoking for at least one day in the past year. Moreover, 16.6% (126/757) had called the quitline before study participation.
Conclusions: We have recruited a diverse sample of individuals who are socioeconomically disadvantaged and designed a rigorous protocol to evaluate the Adapt2Quit recommender system. Future papers will present our main analysis of the trial.
Trial registration: ClinicalTrials.gov NCT04720625; https://clinicaltrials.gov/study/NCT04720625.
International registered report identifier (irrid): DERR1-10.2196/63693.No embarg
ADAM-1: An AI Reasoning and Bioinformatics Model for Alzheimer's Disease Detection and Microbiome-Clinical Data Integration
Full text linkAlzheimer's Disease Analysis Model Generation 1 (ADAM-1) is a multi-agent reasoning large language model (LLM) framework designed to integrate and analyze multimodal data, including microbiome profiles, clinical datasets, and external knowledge bases, to enhance the understanding and classification of Alzheimer's disease (AD). By leveraging the agentic system with LLM, ADAM-1 produces insights from diverse data sources and contextualizes the findings with literature-driven evidence. A comparative evaluation with XGBoost revealed a significantly improved mean F1 score and significantly reduced variance for ADAM-1, highlighting its robustness and consistency, particularly when utilizing human biological data. Although currently tailored for binary classification tasks with two data modalities, future iterations will aim to incorporate additional data types, such as neuroimaging and peripheral biomarkers, and expand them to predict disease progression, thereby broadening ADAM-1's scalability and applicability in AD research and diagnostic applications.No embarg
Repairing the Injured Nervous System: Synaptic Suppression of Axon Regeneration in C. elegans
No full textThe ability of axons to regenerate after injury is critical to restore the connectivity and functionality of damaged neurons. However, axon regeneration in the central nervous system (CNS) is actively inhibited by both intrinsic and extrinsic factors. As a result, CNS injury results in a currently untreatable and permanent loss of function. Developing a complete molecular understanding of how axon regeneration is inhibited is critical to repairing the injured nervous system. From my thesis research, I identified the highly conserved presynaptic protein CLA-
1/Clarinet, the sole C. elegans homolog of mammalian Piccolo and Bassoon, as a novel inhibitor of axon regeneration. Loss of CLA-1 robustly promotes axon regeneration in C. elegans with only minimal disruption of synaptic function in regenerated axons. This provides a unique opportunity to investigate how the canonical function of presynaptic proteins at the neuromuscular junction can be separated from their newly discovered role in axon regeneration. I found that the three splice isoforms of CLA-1 differentially regulate synapse development versus axon regeneration, with the medium isoform CLA-1M being necessary and sufficient to inhibit axon regeneration cell-autonomously. Mechanistically, CLA-1 inhibits regeneration independently of its active zone partner UNC-13/MUNC13, revealing the surprising finding that active zone proteins have evolved multiple strategies to inhibit axon regeneration. CLA-1 inhibits regeneration by downregulating the function of microtubule minus-end binding protein PTRN-1/CAMSAP. In cla-1 mutants, cargo trafficking along microtubules is protected against injury-induced microtubule disruptions to facilitate axon regrowth. Together, my findings add significantly to our current understanding of the role of synaptic proteins in the injury response and reveal a new strategy for promoting both axon regeneration and functional repair.Interdisciplinary Graduate Program2 years2027-06-0
Contrast-Enhanced Mammography: Does Image Acquisition Time and Projection Order Matter?
No full textObjective: To determine reader preference for image order and thus, by inference, image timing after contrast administration that maximizes cancer visualization on contrast-enhanced mammography (CEM).
Methods: This IRB-approved reader study includes consecutive CEMs performed for research or clinical care in patients before a diagnosis of unifocal breast cancer, where the cancer was seen on both craniocaudal (CC) and mediolateral oblique (MLO) recombined images. All CEMs started with the side containing cancer and alternated with the nonaffected side of the same projection. From 2016 to 2018, CC projection was performed first (group 1), and from 2019 to 2020, the MLO projection was performed first (group 2). Five readers evaluated cases for background parenchymal enhancement (BPE) and lesion type. Readers assessed cancer visibility, confidence in margins, and cancer conspicuity using a 5-point Likert scale. Contrast-to-noise (CNR) measurements were also taken.
Results: Seventy-eight female patients were included. Group 1 (CC-first) included 40 patients (51%) and group 2 (MLO-first) included 38 patients (49%). Mean age differed between groups by 5 years (P = .031), otherwise there were no differences in group characteristics. There was an overall preference for earlier-obtained images for cancer visibility, confidence in margins, and lesion conspicuity against BPE (P < .001) and preference for CC projection for lesion conspicuity (P = .045). In 35 instances (35/390, 9%), an individual reader reported a different lesion type on images obtained later, with a majority (28/35, 80%) reporting a less discernible lesion on later-obtained imaging (eg, mass changed to nonmass enhancement).
Conclusion: Our study shows significant reader preference for cancer characteristic evaluation of CEM performed at earlier time points.No embarg
A randomized pilot sleep and circadian behavior clinical trial to improve glycemic and psychological outcomes in young adults with type 1 diabetes (NCT04975230)
Full text linkAims: To investigate the preliminary efficacy of a cognitive behavioral sleep and circadian intervention on glycemic and psychological outcomes in young adults with type 1 diabetes.
Methods: Glycemic and psychological outcomes were evaluated in 39 young adults (mean age 21.08, diabetes duration 11.7 years, mean glycated hemoglobin 8.46 %, 41 % female) from March 2022 to October 2023. Participants were randomly assigned (1:1) to a 12-week cognitive behavioral sleep and circadian condition (n = 21) or a time-balanced attention control condition (n = 18). Data were collected using continuous glucose monitors, research-grade actigraphy, and daily sleep surveys at baseline, post-intervention, and 3-month follow-up.
Results: The cognitive behavioral sleep and circadian intervention condition showed significant improvements in glycemic outcomes, with reductions in the coefficient of variation and mean amplitude of glucose excursions three months post-intervention. It also resulted in decreased diabetes distress at both time points, unlike the Attention Control group, which had minimal changes.
Conclusions: Future research should confirm these preliminary findings in larger, more diverse samples with varied intervention lengths and a longer-term follow-up.No embarg
Genetic testing predicts appearance but not behavior in dogs
Full text linkGenetic tests for behavioral and personality traits in dogs are now being marketed to pet owners, but their predictive accuracy has not been validated. To evaluate the reliability of such tests, we analyzed data from Darwin's Ark, a community science initiative that includes over 3,000 dogs with both genetic data and individual-level behavioral phenotypes. None of the candidate variants had significant associations or predictive power for behavioral traits as previously reported. However, we found strong associations with aesthetic traits that differentiate breeds, such as height, leg length, and ear shape. Our results suggest that earlier studies using breed-average phenotypes, rather than individually measured phenotypes, were confounded by population structure. Behavior in dogs is polygenic and complex, and thus cannot be accurately predicted using tests that consider only a few genetic variants. Furthermore, behavior in dogs is only moderately heritable, and environmental influences inherently limit the potential accuracy of genomic predictions. Developing meaningful, accurate genetic predictions for complex traits that can improve dog health and welfare will require very large cohorts of individually phenotyped dogs.No embarg
Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C
Full text linkBackground: Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials. Several studies have found a protective association in real-world data, but they variously used less recent study periods, correlational methods, and small, local cohorts. Their estimates also varied widely. The real-world effectiveness of Paxlovid remains uncertain, and it is unknown whether its effect is homogeneous across demographic strata. This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing severe COVID-19 outcomes.
Methods and findings: This target trial emulation used a cohort of 703,647 patients with COVID-19 seen at 34 clinical sites across the United States between April 1, 2022 and August 28, 2023. Treatment was defined as receipt of a Paxlovid prescription within 5 days of the patient's COVID-19 index date (positive test or diagnosis). To emulate randomization, we used the clone-censor-weight technique with inverse probability of censoring weights to balance a set of covariates including sex, age, race and ethnicity, comorbidities, community well-being index (CWBI), prior healthcare utilization, month of COVID-19 index, and site of care provision. The primary outcome was hospitalization; death was a secondary outcome. We estimated that Paxlovid reduced the risk of hospitalization by 39% (95% confidence interval (CI) [36%, 41%]; p < 0.001), with an absolute risk reduction of 0.9 percentage points (95% CI [0.9, 1.0]; p < 0.001), and reduced the risk of death by 61% (95% CI [55%, 67%]; p < 0.001), with an absolute risk reduction of 0.2 percentage points (95% CI [0.1, 0.2]; p < 0.001). We also conducted stratified analyses by vaccination status and age group. Absolute risk reduction for hospitalization was similar among patients that were vaccinated and unvaccinate, but was much greater among patients aged 65+ years than among younger patients. We observed disparities in Paxlovid treatment, with lower rates among black and Hispanic or Latino patients, and within socially vulnerable communities. This study's main limitation is that it estimates causal effects using observational data and could be biased by unmeasured confounding.
Conclusions: In this study of Paxlovid's real-world effectiveness, we observed that Paxlovid is effective at preventing hospitalization and death, including among vaccinated patients, and particularly among older patients. This remains true in the era of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron subvariants. However, disparities in Paxlovid treatment rates imply that the benefit of Paxlovid's effectiveness is not equitably distributed.The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, provided funding or data for this study.No embarg
Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study
No full textIntroduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.
Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.
Results: Of 443 patients, 51 (12%) had ASPECTS of 4-5, and 392 (88%) had scores of 6-7. The median age was 65 years (IQR: 46-79), with a balanced sex distribution between the groups. The most common site of initial occlusion was M2 branch in both groups (92% in ASPECTS 4-5 and 85% in ASPECTS 6-7) (p = 0.68). The ASPECTS 4-5 group had lower TICI 2c-3 achievement (31% vs. 55%, p = 0.002) and poorer functional outcomes (mRS 0-1 at 90 days: 12% vs. 29%, p = 0.03) compared to the ASPECTS 6-7 group. Intracranial hemorrhagic complications were higher in the ASPECTS 4-5 group (69% vs. 47%, p = 0.007). Multivariable analysis revealed ASPECTS 6-7 to be associated with higher odds of TICI 2c-3 (OR: 2.5; CI: 1.28 to 4.89, p = 0.007) and lower odds of intracranial hemorrhagic complications (OR: 0.4; CI: 0.19 to 0.81, p = 0.012).
Conclusion: MT may be associated with improved outcomes in patients with moderate-to-low ASPECTS (6-7), though the lack of a control group limits definitive conclusions about its effectiveness. In patients with very low ASPECTS (4-5), higher rates of hemorrhagic complications and poorer outcomes were observed, but this does not necessarily preclude the use of MT. These findings highlight the need for further research and careful patient selection.No embarg
Association Between Residents' Perceived Importance of Family Involvement in Overall Care Planning and Rehabilitative Therapy Administration in Nursing Homes
No full textObjectives: This study examines the association between nursing home residents' perceived importance of family involvement in overall care planning and the administration of physical and occupational therapy.
Design: Cross-sectional study.
Setting and participants: The study focused on all newly admitted nursing home residents aged 50 years and older who transferred from acute-care facilities in 2019.
Methods: We analyzed data from the Minimum Data Set 3.0 for 2,112,330 residents aged 50+ years in US nursing homes. We assessed family involvement in care planning based on the resident's perceived importance of family involvement in care planning, ranging from "Not important at all" to "very important." Exclusions were residents in hospice, comatose, or life expectancy of less than 6 months. The outcome was defined as a sum of physical and occupational therapy minutes. Adjusted linear regression models were used.
Results: Residents who reported "very important" family involvement were older (mean age 78 years) and received more therapy minutes compared with other groups. Those with a lesser preference for family involvement were younger and had higher body mass index, better continence, and less functional impairment. Fewer therapy minutes were received by residents with less family involvement. Residents who considered family involvement "Not Important at All" received 15 fewer minutes of therapy (95% CI, -18 to -13) compared with those who deemed it "very important" after adjusting for confounders.
Conclusions and implications: The study highlights a link between family involvement in care planning and increased therapy administration in nursing homes. Residents reporting higher preference for family engagement received more therapy minutes, with this pattern consistent across various demographic and health conditions. This finding underscores the importance of family involvement in receipt of therapy and highlights the need for incorporating family engagement strategies in nursing home care planning to ensure equitable and effective care.No embarg