Publications by Year: 2026

BACKGROUND: Pallidal deep brain stimulation (DBS) has remarkable effects in patients with cervical dystonia. Yet, its neurophysiological mechanisms are not fully resolved to date. Converging evidence suggests that pallidal DBS modulates sensorimotor and cerebellar network activity in dystonia, possibly by disrupting pathologically enhanced low-frequency oscillations in the basal ganglia. Still, anatomical and electrophysiological findings have rarely been linked, and it is unclear whether oscillatory changes occur in the same network identified in neuroimaging studies.

METHODS: In this cross-sectional study, we investigate the effects of pallidal DBS in patients with cervical dystonia using magnetoencephalography recordings on and off stimulation. We correlated DBS outcomes to the whole-cortex pattern of DBS-induced power changes in each cortical vertex.

FINDINGS: This analysis revealed a distinct low-frequency electrophysiological signature that accounted for significant amounts of variance in DBS improvements across the cohort. The signature was characterised by negative peaks within the supplementary motor area and the motor cortex as well as positive peaks in prefrontal and cerebellar areas.

INTERPRETATION: Our study sheds light on the cortical and cerebellar effects of pallidal DBS on a whole-cortex level and puts emphasis on low-frequency power modulation as a mechanism of effective stimulation beyond the basal ganglia in patients with cervical dystonia. Our findings might inform DBS programming and targeting as well as non-invasive stimulation strategies in the future.

FUNDING: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Project-ID 424778381-TRR 295.

In January 2021, the Centers for Medicare and Medicaid Services (CMS) implemented changes that increased work relative-value units (wRVUs) for outpatient evaluation and management (E/M) services, potentially benefiting cognitive specialties such as pediatric dermatology. This cross-sectional study analyzed 230,524 dermatology outpatient encounters across pediatric, general adult, and micrographic surgery and dermatologic oncology (MSDO) providers at a large academic health system in 2019 and 2021 to assess the impact of these changes. We found that mean wRVUs per encounter increased in pediatric and adult dermatology and decreased for micrographic surgery after the CMS revision (pediatric: 1.3-1.9, p < 0.01; adult: 1.8-2.2, p < 0.01; MSDO: 12.9-12.6, p = 0.048). Both pediatric and adult dermatologists shifted toward billing higher-level E/M codes after the 2021 reforms. These findings suggest that the 2021 CMS reforms modestly narrowed, but did not eliminate-longstanding reimbursement disparities between cognitive and procedural dermatology practices.

BACKGROUND: Surgeon volume and experience may impact patient-reported outcome measures (PROMs) and costs in total knee arthroplasty. However, whether the same relationship exists in unicompartmental knee arthroplasty (UKA) is unclear. We investigated whether surgeon volume and experience drove variations in PROMs or time-driven activity-based costing (TDABC) in UKA.

METHODS: We sourced data from a prospectively maintained multi-institutional arthroplasty registry. Patients completed the Knee Injury and Osteoarthritis Outcome Score - physical function short-form (KOOS-PS) with thresholds for minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). A stratum-specific likelihood ratio analysis was used to categorize surgeons into volume and experience levels: low volume (annual volume less than 16), mid volume (annual volume 16 to 40), and high volume (annual volume greater than 40). The stratum-specific likelihood ratio analysis did not identify meaningful thresholds for surgeon experience. Because not all registry centers perform TDABC, our PROM analysis investigated 794 UKAs performed by 32 surgeons, while our TDABC subanalysis investigated 416 UKAs performed by 12 surgeons. Chi-square tests and one-way analyses of variance compared MCID, PASS, and costs between groups.

RESULTS: Low-volume UKA surgeons were associated with prolonged operating room times (low volume: 110 versus high volume: 73 minutes; P < 0.001) and lengths of stay (low volume: 1.2 versus high volume: 0.6 days; P < 0.001). Both MCID and PASS achievements were similar across volume levels (P = 0.80 and 0.84, respectively). However, low-volume surgeons were associated with increased costs (low volume: 744 versus mid volume: 662 and high volume: 662 cost units; P < 0.001).

CONCLUSIONS: Low-volume UKA surgeons had increased costs. However, MCID and PASS achievements were similar for UKA surgeons of all volume levels. There were no meaningful thresholds for surgeon experience. These results may reassure surgeons of all experience levels to pursue UKAs, while remaining aware of the positive influence of volume on cost-effectiveness.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1 RA) reduce cardiovascular and kidney risk in patients with type 2 diabetes (T2D), yet real-world use remains suboptimal. Remote care models offer a promising approach to improve access; there is limited data on the safety of and adverse events (AEs) associated with prescribing and titrating these therapies through a protocol-driven remote management program.

METHODS: The DRIVE trial was a pragmatic, randomized clinical trial evaluating the safety of a remote disease management program that initiated SGLT2i and/or GLP1 RA in patients with T2D and elevated cardiovascular or kidney risk. Participants were enrolled at a large integrated health care system in Massachusetts between March 2021 and December 2022. Participants were randomized to 1 of 2 implementation strategies: a sequential approach (two months of education first followed by medication initiation) or a bundled approach (simultaneous education and medication initiation). Nonclinical navigators and clinical pharmacists, supervised by physicians, oversaw medication initiation and monitoring under a collaborative drug therapy management agreement and protocol that included algorithms for initiation and titration of SGLT2i and GLP1 RA, as well as adjustment of concurrent glucose-lowering medications to reduce the risk of hypoglycemia Safety outcomes were collected through chart review and patient report, including targeted AEs, hospitalizations, emergency department visits, and urgent care visits. Targeted AEs were prospectively collected over the first 6 months after enrollment: for SGLT2i initiators, symptoms of genital mycotic infection, urinary tract infection, or volume depletion; for GLP 1 RA initiators, nausea, vomiting, diarrhea, and abdominal pain. Hospitalizations, emergency department visits, and urgent care visits over the first 6 months after enrollment were retrospectively collected through electronic health record review.

RESULTS: Of 200 participants enrolled, 106 (53%) initiated SGLT2i (n = 68) or GLP1 RA (n = 40). Among SGLT2i users, 29.4% reported an AE, most commonly genital mycotic infections (10.3%) and symptoms of volume depletion (11.8%); 10.3% discontinued due to AEs. Among GLP1 RA users, 55.0% experienced AEs, predominantly gastrointestinal; 10.0% discontinued due to AEs. No severe hypoglycemia, emergency department visits, or hospitalizations occurred.

CONCLUSIONS: A remote, pharmacist- and navigator-led program safely initiated SGLT2i and GLP1 RA in a high-risk T2D population, with AE rates comparable to clinical trials and high persistence. These findings support the feasibility of remote prescribing with appropriate clinical oversight and structured AE management.

TRIAL REGISTRATION: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/study/NCT06046560; unique identifier: NCT06046560.

BACKGROUND: Post thrombotic syndrome is a fibrotic disease related to inflammation resolution. There are no direct therapies that can ameliorate this disease. Monocyte/macrophages (Mo/MØ) are the primary leukocyte involved with later venous resolution, and likely direct vein wall responses and healing. Herein, we explored the vein wall response with Mo/MØ depletion by two methods.

METHODS: Using two mouse models of venous thrombosis (VT), complete stasis and a flow restricted model, Mo/MØ depletion was accomplished using CD11b-DTR mice administered diphtheria toxin, and clodronate micelle administration in wild type mice. Tissue assays for structural histology, immunohistochemistry and western blotting were performed.

RESULTS: Mo/MØ depletion resulted in significantly less vein wall fibrotic thickness, in the stasis model at day 14 in both the CD11b-DTR mice and those receiving clodronate micelles. No significant effect of Mo/MØ depletion was observed in the flow restricted VT model. The decrease in vein wall fibrosis was associated with fewer DDR2+ vein wall cells in the CD11b-DTR mice, but no difference in endothelial luminal coverage. Decreased cytokine and growth factor expression of IL-6, FSP-1, and VEGFa were associated with Mo/MØ depletion. Lastly, PMN depletion was associated with increased proinflammatory Mo/MØ, and a trend towards increased vein wall fibrosis as compared with controls.

CONCLUSION: Mo/MØ direct the post VT late fibrotic response, possibly by affecting fibroblasts and inflammatory cytokine expression. This effect was only found with the complete stasis model and is consistent with worsened PTS in humans with complete venous obstruction.

Animals achieve high-level goals by sequencing low-level actions. This transformation is best understood in structured tasks that impose a specific mapping between goals and actions. However, it remains unclear whether spontaneous behavior is similarly organized in the service of identifiable goals or how it might be supported by brain regions responsible for goal-oriented behavior, such as the prefrontal cortex (PFC). Here, we show that low-level actions in freely exploring mice are hierarchically organized into seconds-long behavioral states that correspond to task-like programs of behavior. These persistent states structure neural activity in the PFC, which preferentially encodes the identity of states relative to low-level behavioral features and shapes which states are expressed in a given context. These findings argue that spontaneous behavior is organized as a succession of self-directed tasks and identify principles of neural control that are common to structured tasks and spontaneous exploration.

T cells initiate targeted immune responses using T cell receptors (TCRs) to recognize specific antigens. Mapping TCRs to antigens at scale remains a major challenge. Here, we developed an approach to synthesize and functionally screen tens of thousands of TCRs simultaneously. TCR rapid assembly for functional testing (TCRAFT) uses a modular strategy to rapidly and inexpensively construct large pools of TCRs from sequences while maintaining TCRα/β pairing. We applied TCRAFT to reconstruct over 3,800 TCRs from vitiligo blister fluid and mapped these TCRs to specific peptide-major histocompatibility complexes using RAPTR, an activation-based library-on-library screening approach. Vitiligo antigen-specific T cells displayed pronounced clonal expansion and transcriptomic signatures similar to antigen-specific T cells in melanoma, pointing to shared features of disease-relevant T cells in autoimmunity and cancer. Demonstrating scalability, we synthesized and screened over 30,800 TCRs from donors with pancreatic ductal adenocarcinoma to capture antigen-reactive TCRs. Our approach expands the scale and accessibility of TCR-antigen screening, which is critical to understanding immunity and developing new immunotherapies.