Publications by Year: 2026

BackgroundThe Lieber Institute for Brain Development (LIBD) has one of the largest postmortem human brain banks for the study of neuropsychiatric disorders in the world. The postmortem evaluation involves neuropathological assessment for age-related protein accumulations, specifically phosphorylated tau (p-tau) and amyloid-β (Aβ).ObjectivePresent the LIBD semiquantitative assessment methodology for p-tau and Aβ by comparing proteinopathy by age and by apolipoprotein E (APOE) genotype.MethodsPostmortem brain tissue samples were from 1509 people aged 50 or greater (median age at death = 63 years; range = 50-102). Seven brain regions (four neocortical areas, hippocampal formation, midbrain, and cerebellum) were examined by routine histopathology, p-tau immunohistochemistry (AT8; hippocampus and four neocortical samples), and Aβ immunohistochemistry (BAM01; four neocortical samples). APOE genotyping was performed in a subgroup. Semiquantitative assessments include modified CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and modified Braak approaches.ResultsThere were 63.8% rated as B1 (modified Braak I or II), 30.4% rated as B2 (modified Braak III or IV), and 5.8% rated as B3 (modified Braak V or VI). For those in their early 70 s, half had modified Braak stage III-IV ratings. For decedents in their 80 s, approximately 1 in 4 had modified Braak stage V-VI ratings. Aβ was present in 48.8% (C0 = 51.2%, C1 = 17.2%, C2 = 24.5%, and C3 = 7.1%). Age and APOE genotype were significant predictors of Aβ plaques.ConclusionsThe LIBD protocol assessing p-tau and Aβ burden identified significant associations with age and APOE genotype. More research is needed to understand the spectrum of age-related proteinopathy versus neurodegenerative disease neuropathology.

BACKGROUND: Historically, 25-hydroxyvitamin D (25OHD) assays have under- or over-recovered 25-hydroxyvitamin D2 (25OHD2), but assay manufacturers have modified their reagents to address this problem. In this study, we compared the second- and third-generation Roche assays as well as two contemporary offerings from Diasorin and Beckman against liquid chromatography-tandem mass spectrometry (LC-MS/MS).

METHODS: We identified 50 remnant serum samples with 25OHD concentrations from across the analytical range of the second-generation Roche assay. To increase 25OHD2 representation, we identified 25 additional samples from individuals prescribed high-dose vitamin D2 supplements. We tested samples on Roche assays and circulated to laboratories performing Beckman and Diasorin 25OHD assays. We tested samples by LC-MS/MS to obtain concentrations for 25OHD2 and 25-hydroxyvitamin D3.

RESULTS: Mean overall bias for each assay was 5.1 ng/mL or less against the LC-MS/MS measurement; mean proportional bias was 8.7% to 12.1%. Some individual specimens had much larger bias. 25OHD2 was under-recovered on average, but the bias for the third-generation Roche assay represents a significant improvement over the previous assay, and mean bias for current generation assays was no worse than -3.2 ng/mL. In most cases, clinical classification by automated assay values agreed with clinical classification by LC-MS/MS; where present, disagreements occurred near classification thresholds.

CONCLUSIONS: Automated 25OHD assays continue to improve, and 25OHD2 recovery no longer appears to be a significant concern for the assays evaluated here. All assays evaluated were adequate for clinical classification of vitamin D nutritional status and are suitable for routine use, including in patients prescribed high-dose vitamin D2.

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (n = 82, mean age = 39.9 ± 8.5 years, 97.6% White race) were age- and sex-matched to participants without CHD (n = 82, mean age = 40.5 ± 8.1 years, 98.8% White race). Cognitive assessments and Centiloid load (CL) (positron emission tomography) were compared by CHD status.

RESULTS: People with CHD scored lower for visuospatial ability (β = -3.515, p = 0.022) but had higher CL (29.8 ± 12.8 vs. 39.8 ± 12.8, β = 8.00, p = 0.036) and were projected to hit Aβ positivity at a younger age (37.6 and 42.1 years).

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the threshold for an amyloid positivity at a younger age than those without CHDNo differences in cognition were seen in the age- and sex-matched sample based on CHD status; however, the average age of the sample may be too young to see cognitive changesCHDs may influence the timing of Alzheimer's disease (AD) in adults with DS.

OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) is a mainstay of clinical infectious diseases practice, and OPAT-related publications continue to be prominent in journals. The objective of this article is to summarize ten clinically important OPAT-related publications from 2024.

DESIGN: Narrative review.

METHODS: Eighty-one articles were found in a literature search, and 56 met inclusion criteria. A survey containing 25 articles was sent to an email listserv of clinicians with OPAT experience.

RESULTS: This article summarizes the top 10 OPAT articles published in 2024, based on those survey results.

CONCLUSIONS: Common themes from the top 10 OPAT articles published in 2024 included OPAT clinician workload, patient perspectives of OPAT, tools for OPAT work, and dalbavancin use.

BACKGROUND: The substantial health burdens and prevalence of cancer-related pain both during and after treatment underscore the need for expanded access to cancer pain specialists and therapeutic pain treatments. Despite growing demand, cancer pain specialists face substantial barriers to providing effective care.

OBJECTIVE: This exploratory study sought to characterize perspectives from a small group of international pain experts to examine patterns of utilization and perceived accessibility of interventional therapies across cancer types and clinical practice settings.

METHODS: An international, anonymous survey of cancer pain experts, identified via rigorous definition criteria, was conducted using the Qualtrics platform. The survey evaluated eight cancer-related pain categories: head and neck cancer, pleural and rib-based lung cancer, pancreatic cancer, pelvic cancer, lumbosacral spine cancer, extremity cancer, chemotherapy-induced peripheral neuropathy, and bone metastases. Respondents were asked to indicate which treatments they currently use for each type of cancer and which they would use if they had access to them.

RESULTS: Cancer pain experts reported limited access to procedures with greater complexity. Some procedures had substantial variability in use and accessibility, specifically SCS, ITDD, permanent PNS, and nucleus tractus cordotomy. Complementary and alternative therapies were desirable but largely unavailable, particularly in academic settings.

CONCLUSION: Despite the growing need for cancer pain management, specialists continue to face substantial barriers to delivering effective care. This exploratory survey of cancer pain experts identified patterns of reported use and access limitations for therapies across cancer types and practice settings. These findings suggest a relationship between procedural complexity and access barriers, with utilization and availability shaped by institutional resources and practice settings.

BACKGROUND: NKX2-1-related disorders result from heterozygous variants in NKX2-1, a gene crucial for brain, lung, and thyroid development. Although movement disorders, hypothyroidism, and neonatal respiratory distress are recognized, the full phenotype and genotype-phenotype relationships remain incompletely defined.

OBJECTIVES: To delineate neurological, respiratory, and endocrine features across ages, characterize movement disorder trajectories - particularly chorea - and explore genotype-phenotype associations with clinical relevance.

METHODS: We conducted a multicenter, cross-sectional study recruiting participants through referral clinicians and European networks. Standardized clinical and genetic data were captured in an electronic database and analyzed with descriptive and inferential statistics.

RESULTS: Sixty-eight individuals (37 female; median age 16 years, range 2-60 years) were included. Motor delay was the commonest presenting feature ( 60%); neonatal respiratory distress syndrome occurred in one-third of cases. The brain-lung-thyroid triad was present in almost half. Chorea affected over 90% and began in early childhood; it was more frequent with single nucleotide variants than with deletions. Deletions are associated with better gross motor function. Frameshift or nonsense variants showed greater respiratory involvement, and variants in the exon-3 homeobox region were associated with age-related reduction of chorea. Neonatal respiratory distress predicted later respiratory symptoms. Greater abnormal involuntary movement severity correlated with poorer manual and gross motor function. Hypotonia and untreated hypothyroidism are associated with more severe chorea. Psychiatric comorbidity occurred in over one-third of cases, mainly attention-deficit/hyperactivity symptoms.

CONCLUSIONS: This largest cohort to date shows early neurological onset, genotype-specific outcomes, and frequent psychiatric comorbidity in NKX2-1-related disorders, refining clinical expectations and supporting genotype-informed diagnosis, counseling, and management. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.