Publications by Year: 2025

BACKGROUND: Guidelines currently suggest considering EEG guidance during general anesthesia in elderly patients to avoid prolonged burst suppression (BS), with the aim of mitigating postoperative delirium (POD). Our study aimed to investigate the association between POD and intraoperative BS duration dependent on the general anesthetic agent used (propofol vs. sevoflurane).

METHODS: In this prospective study (2019-2022), EEGs from 265 patients over 70 years undergoing general anesthesia were analyzed for intraoperative BS duration both visually and using one new automated algorithm to evaluate its accuracy. Associations between BS duration, anesthetic agent, and postoperative delirium (POD) were evaluated using multivariable logistic regression, adjusting for confounders.

RESULTS: BS duration was markedly shorter than in prior cohorts but did not reduce overall postoperative delirium (POD) incidence. POD occurred more frequently with sevoflurane than propofol (44% vs. 30%, p = 0.017), despite shorter median BS [0 s (IQR 0-4.9) vs. 20.6 s (IQR 0-151.7); p = 0.012]. A significant interaction between anesthetic agent and BS (p = 0.033) showed that BS under sevoflurane conferred 3.8-fold greater POD risk than under propofol. Sevoflurane plus BS increased POD odds 9.3-fold compared to propofol without BS. Our new automated BS detection algorithm demonstrated high precision (median error <2.17 s).

CONCLUSION: Sevoflurane markedly increased POD risk versus propofol, independent of BS duration. Sevoflurane and BS interaction amplified delirium odds. BS appears a vulnerability marker rather than a causal factor. The validated machine-learning BS detector offers a reliable tool for future EEG-based delirium risk research.

BACKGROUND: Effective collateral circulation significantly influences clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We developed and evaluated a composite Perfusion Collateral Impairment Score (PCIS), combining the unfavorable dichotomizations of computed tomography perfusion-derived parameters (hypoperfusion intensity ratio, cerebral blood volume index, and prolonged venous transit), hypothesizing that higher scores, representing worse collateral status, are associated with poor functional outcomes at 90 days.

METHODS: In this multicenter retrospective study, we analyzed 224 patients with acute ischemic stroke due to large vessel occlusion presenting within 24 hours of symptom onset who underwent diagnostic computed tomography perfusion imaging. PCIS was calculated (range 0-3) based on unfavorable values of hypoperfusion intensity ratio (≥0.4), cerebral blood volume index (<0.8), and presence of prolonged venous transit, where each unfavorable parameter is allotted 1 point when present. The primary outcome was 90-day modified Rankin Scale score, categorized as favorable (0-2) and unfavorable (3-6).

RESULTS: Higher PCIS was associated with significantly worse outcomes. The proportion of patients with favorable 90-day outcomes (modified Rankin Scale 0-2) declined from 62% with PCIS 0 to 23% with PCIS 3 (P = 0.001). Multivariable analysis demonstrated that each 1-point increase in PCIS was independently associated with reduced odds of functional independence (adjusted odds ratio [OR], 0.60; 95% CI, 0.39-0.90; P = 0.015). Predicted probabilities of unfavorable outcome (modified Rankin Scale score 3-6) ranged from 38.2% (95% CI, 26.7-49.8) in PCIS 0 to 77.3% (95% CI, 59.8-94.8) in PCIS 3. The association between PCIS and outcomes persisted across treatment groups.

CONCLUSIONS: The PCIS, integrating 3 perfusion-based collateral parameters, is associated with 90-day functional outcomes in patients with acute ischemic stroke due to large vessel occlusion. This scoring system offers a prognostic tool to identify patients at higher risk for poor outcomes and may be useful for optimizing resource allocation. Prospective validation is warranted.

BACKGROUND: Recent trials of endovascular thrombectomy (EVT) for acute distal medium vessel occlusions (DMVOs) were negative but also used inconsistent imaging-based inclusion criteria, whereas many successful large vessel occlusion (LVO) EVT trials used empirically validated perfusion imaging-based target mismatch (TMM) criteria: an ischemic penumbra (time-to-maximum [Tmax] >6 s) to core (relative cerebral blood flow [rCBF] <30%) mismatch ratio ≥1.8 and mismatch volume ≥15 mL. We aimed to determine optimal corresponding definitions in DMVOs to improve patient selection for EVT.

METHODS: We retrospectively analyzed patients with acute anterior DMVOs from prospectively collected databases at 4 comprehensive stroke centers. To assess core, we evaluated how well pretreatment rCBF <20%, <30%, <34%, and <38% volumes correlated with magnetic resonance imaging-based posttreatment follow-up infarct volumes in successfully recanalized patients. To evaluate penumbra, we assessed how well pretreatment Tmax >4 s, >6 s, >8 s, and >10 s volumes correlated with follow-up infarct volumes in unrecanalized patients. Then, we evaluated whether these improved parameters for core and penumbra better quantified LVO TMM and identified an optimal DMVO TMM definition.

RESULTS: In 122 core (recanalized) patients, rCBF <38% most strongly correlated with follow-up infarct volumes (concordance correlation coefficient 0.30 [95% CI, 0.15-0.48]), outperforming rCBF <30% (concordance correlation coefficient 0.21 [0.10-0.35]) (P<0.001). In 70 penumbra (unrecanalized) patients, Tmax >8 s most strongly correlated with follow-up infarct volumes (concordance correlation coefficient 0.49 [0.25-0.77]), outperforming Tmax >6 s (concordance correlation coefficient 0.39 [0.17-0.68]) (P<0.001). In 180 patients undergoing EVT with Tmax >6 s to rCBF <30% mismatch ratio ≥1.8 and mismatch volume ≥15 mL, recomputing mismatch ratio and mismatch volume using Tmax >8 s and rCBF <38% separated those with favorable outcomes (P = 0.007), and Tmax >8 s to rCBF <38% mismatch ratio ≥2.2 and mismatch volume ≥10 mL maximally separated them (P<0.001, absolute risk reduction 26%).

CONCLUSION: In acute anterior DMVOs, rCBF <38% and Tmax >8 s best correspond to ischemic core and penumbra, respectively; more favorably quantify LVO TMM; and reveal optimal TMM criteria. These results should be prospectively investigated as inclusion criteria for EVT in this population and suggest recent negative DMVO EVT trials may have been confounded by suboptimal patient selection.

Background/Objectives: Speech and motor control share overlapping neural mechanisms, yet their quantitative relationships in Parkinson's disease (PD) remain underexplored. This study investigated bidirectional associations between acoustic voice features and objective motor metrics to better understand how vocal and motor systems relate in PD. Methods: Cross-sectional baseline data from participants in a randomized neuromodulation trial were analyzed (n = 13). Motor performance was captured using an Integrated Motion Analysis Suite (IMAS), which enabled quantitative, objective characterization of motor performance during balance, gait, and upper- and lower-limb tasks. Acoustic analyses included harmonic-to-noise ratio (HNR), smoothed cepstral peak prominence (CPPS), jitter, shimmer, median fundamental frequency (F0), F0 standard deviation (SD F0), and voice intensity. Univariate linear regressions were conducted in both directions (voice ↔ motor), as well as partial correlations controlling for PD motor symptom severity. Results: When modeling voice outcomes, faster motor performance and shorter movement durations were associated with acoustically clearer voice features (e.g., higher elbow flexion-extension peak speed with higher voice HNR, β = 8.5, R2 = 0.56, p = 0.01). Similarly, when modeling motor outcomes, clearer voice measures were linked with faster movement speed and shorter movement durations (e.g., higher voice HNR with higher peak movement speed in elbow flexion/extension, β = 0.07, R2 = 0.56, p = 0.01). Conclusions: Voice and motor measures in PD showed significant bidirectional associations, suggesting shared sensorimotor control. These exploratory findings, while limited by sample size, support the feasibility of integrated multimodal assessment for future longitudinal studies.

Event-related spectral perturbations (ERSPs) capture dynamic changes in electroencephalography (EEG) power across frequency and trial time. Even though they are obtained at the trial level, they are commonly averaged across trials and analyzed at the subject level for enhancing the signal-to-noise ratio. While evoked activity is stimulus-locked, representing the brain's predictable response to stimuli, induced signals that are not strictly locked to stimulus presentation are thought to be generated by higher-order processes, such as attention and integration. Motivated by joint modeling of multilevel (trials nested in subjects) and multivariate (evoked and induced) ERSP data from a visual-evoked potentials (VEP) task, we propose a multilevel multivariate functional principal components analysis (FPCA) for high-dimensional functional outcomes as a function of time and frequency. The proposed estimation procedure utilizes multilevel univariate FPCA decompositions along each variate of the multivariate outcome using fast covariance estimation and incorporates the dependency across outcome variates at each level of the data. Hence, the proposed approach for multilevel multivariate FPCA can efficiently scale up to higher dimensional functional outcomes and increasing number of variates in the multivariate functional outcome vector. Extensive simulations show the efficacy of the proposed approach, while applications to VEP data lead to new insights on autism-specific neural activity patterns. The autistic group shows significantly lower evoked and higher induced gamma power compared to the neurotypical group. In addition, while subject level variation is dominated by variation in the stimulus-locked evoked signal in neurotypical development, it is dominated by induced power in autism.

Lymphovenous anastomosis (LVA) has emerged as an important physiologic microsurgical procedure for patients with breast cancer-related lymphedema (BCRL) with the goal of restoring lymphatic drainage rather than providing just palliative care for symptoms of swelling. A multicenter randomized controlled trial (RCT) in 2024 (N-LVA) found improvements in the Lymph-ICF physical and mental function domains, and decreased use of compression garments, despite modest changes in total quality of life (QoL) and limb volume at 6 months. Meta-analyses have found average reductions of 30%-35% in excess limb size and nearly two fewer cellulitis episodes per year after LVA and vascularized lymph node transfer (VLNT). As the surgical technology continues to improve (e.g., prophylactic LYMPHA procedures, high-resolution lymphatic imaging, robotic supermicrosurgery) and as LVA becomes more widely adopted within experienced surgical centers, precision surgery will be increasingly considered in lymphedema care. Collectively, these advancements represent a movement toward physiologic reconstruction in lymphedema care and the next initiatives will focus on patient selection and eligibility optimization, state-of-the-art surgical technology optimization, and standardizing outcome measures to achieve sustained improvements in QoL.

Background/Objectives: This study explores the perceptions, experiences, and expectations of pediatric healthcare professionals regarding the implementation of virtual visits (VVs) in routine pediatric practice. Methods: Using the Consolidated Framework for Implementation Research (CFIR) to analyze individual, organizational, and contextual factors influencing the adoption of pediatric virtual visits, we conducted a descriptive cross-sectional survey distributed nationwide among pediatricians, pediatric nurses, and residents. Results: A total of 308 Spanish healthcare professionals correctly completed the REDCap survey and were included in the analysis. The mean age was 44.3 years, and respondents represented both hospital-based (55.8%) and primary care professionals (44.2%). Overall, 74.8% had previous experience with telephone consultations, while only 11% had performed virtual visits. Most professionals believed VVs could be useful in primary care (81.3%) and hospital out-patient settings (73.9%), especially for follow-up appointments, communication of test results, and chronic-care monitoring. VVs were perceived as more appropriate for older children and adolescents than for infants. Major concerns included poor internet connection (52.6%), and data security (37.4%); however, a particularly relevant finding was the low confidence in using digital tools, particularly among older professionals. Comparative analyses by age and workplace setting identified differences in interest, perceived barriers, and access to technical resources. Hospital-based clinicians reported greater interest in adopting VVs and better access to technological resources compared with primary care professionals. The professionals' age was inversely associated with interest in VVs. Notably, 72.6% of respondents expressed interest in receiving specific VV training, and nearly 90% believed virtual visits should be offered in their workplace. Conclusions: These findings show a high overall acceptance of VVs but also underline persistent barriers related to infrastructure, digital literacy, and clinical applicability in younger children. Addressing these obstacles through training, improved equipment, and clear clinical protocols will be essential for the successful implementation of pediatric VV programs.

Treatment approaches to childhood T-cell lymphoblastic lymphoma (T-LL) are based on those used for T-cell acute lymphoblastic leukemia (T-ALL), but reports of outcomes with contemporary regimens are limited, as patients with LL are often excluded from ALL clinical trials. In this study, we retrospectively analyzed the characteristics and outcome of a cohort of 23 pediatric patients with T-LL treated between 2006 and 2020 according to Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols. Five-year event-free survival, overall survival, and disease-free survival rates were 78.3% (95% CI: 55.4%-90.3%), 87.0% (95% CI: 64.8%-95.6%), and 90% (95% CI: 65.6%-97.4%), respectively. Morphological marrow disease (defined as 5%-24% blasts) at diagnosis was the only feature associated with adverse prognosis. Treatment based on DFCI ALL protocols is an effective strategy for childhood LL and should be considered at the time of treatment selection.