Publications by Year: 2026

OBJECTIVE: To identify perceived benefits, concerns, and challenges to adolescents with cancer accessing online patient portals.

STUDY DESIGN: Semi-structured, qualitative interviews with 48 dyads of adolescents with cancer (12-17 years) and their parents. Interviews explored parental and adolescent experiences, motivations, and concerns to accessing the portal. Three team members analyzed interview transcripts using thematic analysis.

RESULTS: Most adolescents (41/48, 85%) and parents (42/48, 87.5%) believed that adolescents should have access to their electronic health information (EHI), but that access should depend on certain factors, such as the adolescent's age, maturity level, or ability to understand portal content. Although most parents reported having accessed the portal (42/48, 88%), only 12 adolescents (25%) had previously accessed the portal. We identified seven themes related to both real-life and hypothetical benefits and concerns of adolescent portal access: promoting communication between adolescents, caregivers, and clinicians; providing reassurance to adolescents; supporting adolescent engagement and responsibility; supporting adolescent knowledge and understanding; creating confusion or misunderstanding; creating worry or fear; and potential for misuse.

CONCLUSION: In our qualitative study, most adolescents with cancer and their parents believed that teens should have access to their EHI but expressed a diversity of opinions on when and under what circumstances teens should have access. Both parents and teens recognized that portals had the potential to both alleviate and contribute to anxiety and worries related to cancer care and prognosis. Our study found novel areas of concern relating to the potential for portal use to negatively impact adolescent mental health.

Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.

The transition from trainee to independent investigator is one of the most challenging and formative phases of a scientific career. It requires not only scientific expertise but also the skills to lead, mentor, manage, and communicate effectively. The Arthur and Sandra Irving Cancer Immunology Symposium serves as a platform for established investigators to mentor trainees and early-career faculty as they navigate this transition to independence. Through sharing personal experiences and lessons from their own careers, senior leaders provide guidance on the scientific, professional, and personal challenges that shape a successful career in cancer immunology-emphasizing how curiosity, persistence, and a translational mindset can make a lasting real-world impact. This commentary highlights key themes, including leadership, communication, recruitment, and fundraising. Altogether, these insightful thoughts provide a framework for the next generation of cancer immunologists as they establish their independent careers as future leaders in the field.

BACKGROUND: The use of artificial intelligence (AI) in medicine has surged. Given the sensitive nature of palliative care, it is crucial to apply AI tools in a patient-centered and ethical manner.

AIM: We sought to understand the ethical implications of implementing AI-based tools in palliative care from various stakeholders.

DESIGN: Using a framework of ethics of care, we conducted thematic analysis to identify emerging themes.

SETTING/PARTICIPANTS: We recruited and interviewed 22 participants: six patients, four care-partners, five clinicians, three bioethicists, and four clinician-bioethicists, recruited through a single hospital clinic for patients and care-partners and purposeful snowball sampling for clinicians and bioethicists based on their knowledge and interest in AI-based tools. The mean age of participants was 48 years old; 64% were male. Clinician participants had practiced for a mean of 11 years, and ethicists for 15 years. We aimed to recruit clinicians and bioethicists from multiple states and specialties.

RESULTS: From the interviews we extracted five main themes: (1) Primacy of the doctor-patient relationship over AI performance; (2) Humans have intuition and nuance that AI lacks; (3) Agreement about the importance of oversight of AI tools; (4) New AI technologies should include a process for patient education; and (5) AI increases efficiency, scalability, and a more unified approach to serious illness.

CONCLUSIONS: When building and implementing AI-based tools, we recommend: establishing oversight committees; reflecting on the unique contributions of humans to care; proactively educating patients and contextualizing the tools; and ensuring data use is restricted to clinical care.

BACKGROUND: People experiencing homelessness are disproportionately affected by opioid use disorder (OUD), yet treatment engagement remains low. Understanding opioid-related health beliefs in this population may inform more tailored interventions.

OBJECTIVE: To characterize opioid-related health beliefs among homeless-experienced individuals with OUD and examine their alignment with opioid use severity.

METHODS: We conducted a cross-sectional survey of individuals initiating opioid treatment at a homeless healthcare program in Boston, Massachusetts. The survey assessed key Health Belief Model domains related to opioid use and incorporated the World Health Organization's Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) to quantify opioid use severity. We used nonparametric trend tests to examine associations between ASSIST quartiles (Q1 ≤ 23.5, Q2 23.6-33.0, Q3 33.1-38.0, and Q4 > 38.0) and belief domains.

RESULTS: Among 148 participants, the mean age was 41.7 years; 51.4% identified as White, 16.2% as Black, and 38.5% as Hispanic. Higher ASSIST quartiles, indicating higher opioid use severity, were significantly associated with greater perceived threat, including being very worried about opioid use (25% in Q1 vs. 72.7% in Q4; p = 0.001), perceiving very high overdose risk (4.2% vs. 40.9%; p = 0.006), and viewing overdose as very dangerous (87.5% vs. 100%; p = 0.036). Higher ASSIST quartiles were also significantly associated with greater perceived benefits, including that abstaining from opioids (78.3% vs. 100%; p = 0.004) and taking MOUD (69.6% vs. 95.2%; p = 0.016) would improve quality of life.

CONCLUSIONS: Individuals with greater opioid use severity endorsed higher perceived opioid-related threats and treatment-related benefits. Interventions that highlight these beliefs may help enhance treatment engagement in this high-risk population.

OBJECTIVE: Focal hand dystonia (FHD) severely impairs task-specific motor control, yet the optimal surgical target for stereotactic intervention remains uncertain. This study aimed to identify the precise thalamic lesion site associated with symptomatic improvement and to clarify its network connectivity.

METHODS: We retrospectively analyzed 164 patients with FHD (mean age = 42.0 years, 26.2% women) who underwent stereotactic thalamotomy of the ventral lateral thalamus. Voxel-wise probabilistic lesion mapping was applied to relate lesion locations to clinical outcomes. Structural connectivity analyses assessed fiber tracts linked to the optimal lesion site. Model performance was evaluated by 10-fold cross-validation, validation in an out-of-sample cohort, and testing in reoperation cases.

RESULTS: We identified that lesioning the border zone between the ventralis oralis posterior (Vop) and ventralis intermedius (Vim) nuclei was associated with improvement of FHD. The predictive model achieved high accuracy in cross-validation (area under the curve [AUC] = 0.836) and performed robustly in independent validation. Connectivity analyses showed that the Vop-Vim border zone was linked to cerebellothalamic and pallidothalamic afferents as well as thalamocortical projections to the supplementary motor area and premotor cortex. In contrast, lesions extending into the ventralis oralis anterior nucleus were associated with an increased risk of motor complications.

INTERPRETATION: Precise targeting of the Vop-Vim border maximizes clinical benefit while minimizing adverse effects in FHD thalamotomy. These findings establish the first evidence-based thalamic target for FHD, offering practical guidance for stereotactic interventions and advancing understanding of dystonia pathophysiology. ANN NEUROL 2026.

BACKGROUND: Psoriasis and depression frequently coexist, creating a complex, bidirectional relationship that complicates treatment. This study, integrating clinical assessments with transcriptomic and metabolomic analyses, hypothesizes that TYK2 (tyrosine kinase 2) inhibitors possess a dual therapeutic potential to simultaneously address both dermatological manifestations of psoriasis and the frequently accompanied depressive symptoms.

METHODS: In a cohort of 298 psoriasis patients evaluated using the Hospital Anxiety and Depression Scale (HADS), participants were categorized into a TYK2 inhibitor group, a Janus kinase (JAK) inhibitor group, and a non-JAK pool (comprising interleukin [IL]-23 biologics, IL-17 biologics, and other treatments) to avoid overlapping JAK pathway inhibition. Statistical analysis was conducted using generalized linear models (GENMOD), with adjustments for the following covariates: age, sex, Psoriasis Area and Severity Index (PASI), body surface area (BSA), prior systemic or biologic therapy within 12 months, disease duration, and phototherapy history.

RESULTS: For HADS-D scores, the TYK2 inhibitor group showed significantly lower values compared with the non-JAK pool (β = 1.23, 95% confidence interval [CI]: 0.37-2.10). However, no significant differences were observed when compared with the IL-23 biologics group (β = 0.67, 95% CI: -0.76-2.10) or the JAK inhibitor group (β = 0.84, 95% CI: -1.54-3.21). Transcriptomic analysis of peripheral blood revealed significant downregulation of genes related to the IL-6 receptor, long-term depression pathways, and Th17 cell differentiation, while pathways associated with neuronal activity were upregulated. Metabolomic profiling highlighted a decrease in kynurenic acid, which is known for its pro-inflammatory and depressive effects, and an increase in 1H-indole-3-propanoic acid, an anti-inflammatory metabolite with neuroprotective properties. It is important to note that these findings are based on exploratory omics analyses, for which false discovery rate (FDR) control was applied.

CONCLUSIONS: These findings provide a hypothesis that TYK2 inhibitors disrupt the persistent "peripheral inflammation-central depression" cycle by targeting the IL-23/Th17 axis and modulating the IL-6/tryptophan metabolic hub. This innovative, multi-targeted approach represents a possibility for treating psoriasis with comorbid depression, offering not only clinical improvements in both skin and mood symptoms but also enhanced patient adherence to treatment regimens.

Astrocytes are glial cells in the brain essential for maintaining neural homeostasis, modulating synaptic activity through gliotransmission, and supporting metabolic processes. As part of Alzheimer's disease (AD) progression, astrocytes undergo significant morphological and functional changes, transitioning to reactive states that can contribute to both neuroprotection and neurodegeneration. This review aims to summarize current knowledge on the roles of astrocytes in AD, focusing on their contributions to amyloid-β (Aβ) and tau pathologies, neuroinflammation, disrupted calcium signaling, and age-related changes. We synthesized findings from published studies investigating astrocytic sodium channels (Nav1.6), key molecular pathways such as apolipoprotein E (ApoE), oxidative stress, and excitatory amino acid transporter 2 (EAAT2), as well as emerging astrocytic biomarkers including GFAP, YKL-40, and MAO-B. Optogenetic studies and other experimental approaches with high spatiotemporal resolution were also considered to understand astrocyte involvement in circuit impairments and sleep deficits in AD. Astrocytes in AD exhibit altered calcium signaling, impaired gliotransmission, and dysregulated sodium channel activity. Reactive astrocytes influence Aβ and tau pathology, contribute to neuroinflammation, and show altered biomarker expression. Molecular dysfunctions, including changes in ApoE, EAAT2, and oxidative stress pathways, exacerbate disease progression. Emerging therapeutic strategies targeting astrocytic pathways, such as siRNA therapy and gene editing, show promise for mitigating these pathological changes. Understanding the complex roles of astrocytes in AD highlights their dual protective and detrimental functions and identifies novel avenues for therapeutic intervention. Targeting astrocytic dysfunction may offer strategies to slow disease progression and improve cognitive outcomes.

Objective The aim of this study was to examine whether the intake of folate, vitamin B6, and vitamin B12 before and after disease diagnosis impacts the risk of death among individuals with Parkinson's disease (PD). The impact of folate, vitamin B6, and B12 intake on mortality in individuals with PD is unknown. Methods The study population comprised 1521 participants of two large prospective cohorts who were newly diagnosed with PD during follow-up. Participants responded to repeated dietary assessments using validated food frequency questionnaires, covering up to 30 years before to more than 10 years after PD diagnosis. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of death according to quartiles of the cumulative average intake of B vitamins before and after disease diagnosis. We also examined PD-specific mortality and alternative exposure definitions. Results We documented 1005 deaths during 15 years of follow-up. A higher cumulative average intake of B vitamins before disease diagnosis was associated with a lower risk of death among patients with PD. The multivariable-adjusted HR (95% CI) of death comparing top to bottom quartiles of intakes was 0.78 (0.62-0.99) for folate, 0.76 (0.62-0.93) for B6, and 0.86 (0.69-1.09) for B12. These estimates were stronger in analyses restricting to intakes from supplemental sources and in those considering intakes reported up to 12 years before diagnosis. The intake of these B vitamins after PD diagnosis was not associated with the risk of death. Conclusions Higher intake of B vitamins before disease diagnosis, particularly folate and vitamin B6, may decrease the risk of death in individuals with PD. Postdiagnosis intake did not appear to impact survival.