Publications by Year: 2025

Anti-LGI1 encephalitis is an autoimmune disorder of the brain, characterized by subacute cognitive impairment, faciobrachial dystonic seizures, and hyponatremia. Although rare, recent reports suggest that LGI1 encephalitis may be triggered following COVID-19 exposure whether through infection or vaccination. It usually presents with insidious progression which, along with old age predominance, may delay the diagnosis. We herein report a 67-year-old patient with positive LGI1 antibody titers, who developed subacute parkinsonism after serial COVID-19 vaccination. To our knowledge, this is the first documented case report highlighting a potential association between COVID-19 vaccination and the development of parkinsonism in the context of LGI1 encephalitis.

Individuals with cancer are at increased risk of severe COVID-19 and immunogenicity of SARS-CoV-2 vaccines may be compromised, especially in those receiving systemic anti-cancer treatment. Understanding how treatment affects vaccine-induced humoral responses is critical to optimize vaccination strategies in this vulnerable population. This study evaluated neutralizing antibody responses to SARS-CoV-2 vaccination in cancer cohorts undergoing active treatment or not, measured at multiple timepoints before and after vaccination using a pseudovirus-based neutralization assay. We observed significantly lower seroconversion rates and impaired neutralizing antibody responses in the cancer cohort on active treatment compared to those not on treatment, suggesting an association between active treatment and a compromised functional immune response. Although strong correlations between anti-spike IgG and neutralizing antibodies were observed across all groups, regression analyses revealed potential differences in the relationship between binding and functional antibodies. We also observed the correlation between avidity and neutralizing antibodies varied across groups. These findings suggest that active systemic therapy impaired both the quantity and quality of antibody responses. Tailored vaccination timing and monitoring may be critical in reducing the risk of severe COVID-19 symptoms and improving COVID-19 vaccine efficacy in this population.

We report an 87-year-old female with a history of intellectual disability, severe speech impairment and behavioral issues. She was globally delayed in childhood. In adolescence, she had hallucinations, behavioral issues and was institutionalized. Her behavioral issues were treated, and her medical and behavioral course was stable until her 80's when she began to decline cognitively. She died at age 87. Exome sequencing revealed a novel predicted damaging missense variant (c.1913T>G; p.Met638Arg; NM_001136196.2) in the gene encoding Transportin-2 (TNPO2). Heterozygous variants in TNPO2 have been recently associated with an intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (IDDHISD; MIM:619556). Postmortem pathological examination of her brain revealed focal neuronal depletion in the dentate gyrus, CA1, and hilar regions of the hippocampus. These findings are consistent with human gene expression data showing normal to increased expression of TNPO2 in the dentate gyrus and CA1 region of the hippocampus. We suggest that the p.(Met638Arg) variant in TNPO2 is potentially disease-causing and associated with IDDHISD.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare but distinct disease that remains poorly understood, especially at proteome level. We report comprehensive mass spectrometry-based proteomic analyses of SPN (n = 13) and characterize differences from other pancreatic neoplasms, pancreatic ductal adenocarcinoma (n = 11) and neuroendocrine tumor (n = 10). We discovered that the SPN proteome is uniquely distinct from that of other pancreatic neoplasms. Lysosome-related proteins are enriched and upstream lysosomal processes transcriptional regulators, MITF and TFE3, are overexpressed in SPN. MITF protein expression is more specific for SPN than TFE3, previously considered the most specific immunohistochemical marker. Since lysosomal-related processes are connected to biological energy generation processes, we profiled metabolic pathways and found that SPN is characterized by higher fatty acid oxidation and lower glycolysis than PDAC and high proteasome pathway activity with many proteasomal proteins upregulated, suggesting a possible link to metabolic adaptation mechanisms in low-nutrient environments. Proteomics characterizes SPN as an immune-cold tumor with low MHC class I expression. Proteome-based receptor tyrosine kinase (RTK) pathway profiling suggests PDGFRA and ERBB2 (HER2) as potential candidates for targeted therapy. Our results provide unique proteomic contribution to the understanding of SPN biology and highlight differences from other pancreatic tumors.

OBJECTIVE: In the context of cancer, pain demands interpretation. Our research has found that fear of cancer recurrence (FCR) is associated with the tendency to interpret ambiguous information as health-related. We aimed to determine whether we could modify these interpretation biases to improve FCR, and pain outcomes.

METHODS: We conducted a double-blind randomized controlled trial comparing two fully automated Cognitive Bias Modification for Interpretation (CBM-I) programs to a matched sham. We randomized 174 people with breast or ovarian cancer to one of three groups (pain-related CBM, cancer-specific CBM or sham). Participants completed four training sessions, and outcomes were assessed before and after intervention and 2 weeks later. We nominated co-primary outcomes as FCR and fear of progression (FoP) so that measures were suited to those with and without active disease and measured pain outcomes and other secondary psychosocial outcomes.

RESULTS: We analyzed data using mixed-model linear regression and intention-to-treat. Results indicated that both the cancer-specific and pain-related training groups showed significant improvements in FCR (F(2,440) = 17.19, p < 0.0005) and FoP (F(2,440) = 15.03, p < 0.0005) over time compared to sham. Both versions of CBM were associated with benefits in pain intensity (F(2,440) = 6.14, p < 0.0005) and pain interference (F(2,440) = 5.223, p = 0.001) compared to sham. No other secondary outcomes improved.

CONCLUSION: CBM for interpretation is an efficacious treatment for FCR, FoP and pain outcomes in ovarian and breast cancer. This intervention was delivered wholly online, had high completion rates (80%) and therefore is highly scalable. CBM-I could be part of a stepped care model to meet the large unmet need for people who are living with and beyond cancer.

BACKGROUND: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination. Our study tested the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied, via a series of cross-sectional EWAS, conducted in two population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (My Body My Story:: n = 224 Black NH and 69 white NH;; and the Multi-Ethnic Study of Atherosclerosis:: n = 229 Black NH, n = 555 white NH and n = 191 Hispanic). Genome-wide changes in DNAm were measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450 k BeadChip (MESA; using purified monocytes).

RESULTS: We observed the strongest associations with traffic-related air pollution (between 0 and 22 DNAm sites associated at p < 2.4e-07, measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. However, we did not replicate previous air pollution EWAS findings. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g. for Black NH participants, in MBMS born in a Jim Crow state associates with a DNAm site in ZNF286B at p = 8.43E-08; and in MESA adult exposure to racialized economic residential segregation associates with a DNAm site in FUT6 at p = 4.05E-08) situated in genes with plausible links to effects on health.

CONCLUSIONS: Overall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution (of which distribution of exposure is inequitable) become embodied and may lead to health inequities. Due to the extensive range of exposures we tested, further replication in additional studies and other tissues is warranted.

BACKGROUND: Healthcare providers and policymakers worldwide differ in their provision of access to adolescent patients' electronic health records (EHR). The regulatory framework in Sweden restricting both guardians' and adolescents' online record access (ORA) has during recent years received criticism. The aim was to quantitatively and qualitatively, explore attitudes about ORA and perceptions about ORA regulations among pediatric oncology healthcare professionals (HCPs) in Sweden.

METHODS: A convergent mixed-methods design (QUAL, quan) was used, consisting of a survey study (N = 95) and semi-structured individual interviews (N = 13). Physicians and nurses in pediatric oncology were recruited in clinics face-to-face or via staff e-mail. Descriptive statistics were used to present quantitative survey results. Interviews were recorded, transcribed, and analyzed using content analysis.

RESULTS: A majority of participants (72%) were critical of the access restrictions but lacked knowledge about access extensions, with more than 60% unaware of application procedures. Five themes emerged regarding both perceived benefits and risks of ORA. Examples of benefits included adolescent empowerment, parental support, and improved partnership; risks included an increased emotional distress and confusion among young patients and their guardians, increased workload for HCPs, and threats to adolescent confidentiality. An additional five identified themes captured HCPs' views on regulations and included uncertainty, variation among adolescents, and the need to balance parental support and adolescent privacy.

CONCLUSIONS: Findings indicate lacking knowledge about ORA regulations and little incentive for HCPs to promote its use. While risks of ORA were often directly experienced and concerned confidentiality breaches and difficulties with EHR documentation, benefits tended to be anticipatory and related to patient or parent experiences. Still, HCPs showed limited support for ORA restrictions during adolescence. To ensure safe and effective ORA use, HCPs need clearer guidance and support.

TRIAL REGISTRATION: Not applicable.

BACKGROUND: Changes in the population pyramid and in the disease burden of patients can be observed through the expenditure and frequency of use of medical imaging in health systems; however, this topic has undergone little study in the international literature. Our objective was to analyze the per capita and total expenditure and the frequency of use of radiological imaging according to gender, geographic area and type of medical imaging in the Colombian population.

METHODS: In this work, a national database was used to study temporal dynamics of annual expenditures and frequency of use on medical imaging of more than 19 million people (0-100 years old). Descriptive analytical techniques and statistical visualization were used for the development of the research.

RESULTS: Per capita expenditure increased progressively with age and for almost all ages it was found to be higher in men than in women. In addition, rural areas had a higher per capita expenditure on medical imaging than urban areas. However, when analyzed by total expenditures, women and urban areas had the highest participation. Interventional radiology and magnetic resonance imaging procedures accounted for the largest share of total medical imaging spending. General radiology medical imaging has the highest frequency of use per capita and urban women are the profile with the highest use of these medical services.

CONCLUSION: Our findings enable further characterization of the evolution of the financial burdens of medical imaging which we anticipate increasing with future aging of the population.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12962-025-00681-1.

Within the cellular milieu, protein molecules must fold into precise three-dimensional structures to attain functionality. Protein chains can assume many misfolded states during this critical process. Such errant configurations are unstable and can aggregate into toxic misfolded conformations. In protein misfolding disorders, polypeptides are folded in an aberrant manner, resulting in non-functional and often pathogenic states. Protein folding is fundamental to biological function, and disruption of the process can result in toxic aggregates, such as oligomers and amyloid fibrils, which are implicated in a variety of diseases, particularly neurodegenerative diseases such as Alzheimer's and Parkinson's. Here, we examine the delicate interplay of forces that determine the native conformation of proteins and how perturbations in this balance lead to disease. A critical aspect of our discussion is the cell's proteostasis network, a complex network of molecular chaperones and regulators responsible for regulating protein folding and maintaining the health of the cell. In this chapter, we discuss how intrinsic protein properties, post-translational modifications, and extrinsic environmental factors can destabilize proteins, thereby resulting in their misfolding. Several pathogenic mechanisms will be elucidated, including the progression from a misfolded protein to the development of disease phenotypes. Next, the chapter will present an overview of the current therapeutic approaches to mitigate the diseases caused by protein misfolding. Using the latest findings in clinical and experimental research, we will evaluate the therapeutic landscape, ranging from small-molecule inhibitors to chaperone-based therapies.

BACKGROUND: Anorexia nervosa (AN) in older adults presents with medical complexity, psychiatric comorbidity, and diagnostic ambiguity, often overlapping with depression, cognitive decline, or anorexia of aging. A literature base dominated by case reports limits practical guidance for consultation-liaison (C-L) psychiatry.

OBJECTIVE: To describe key clinical features of AN in older adults, integrating systems-level barriers that shape diagnosis, care transitions, and prognosis.

METHODS: We describe 2 late-life AN cases and conducted a systematic review of studies including adults aged ≥60 years with AN defined by the Diagnostic and Statistical Manual of Mental Disorders. Two reviewers independently screened and extracted data and appraised quality using Joanna Briggs Institute tools. Extracted variables included demographics, Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria, psychiatric and medical comorbidities, care setting, and outcomes. We used narrative synthesis with descriptive statistics like n/N, %, median (interquartile range), and ranges to summarize case reports. The AN course was categorized as late-onset (≥60 years), chronic diagnosed, chronic undiagnosed, or recurrence.

RESULTS: Forty publications met criteria: 31 case reports/series, eight cross-sectional studies, and one cohort. Cross-sectional studies showed 3-6% prevalence of disordered eating behaviors with rare AN. Across 47 individually described patients, most were women in their early seventies with severe undernutrition and multimorbidity. Care most commonly occurred on medical units. Nutritional rehabilitation (e.g., supervised meals, enteral feeding) was the most common intervention. Outcomes were mixed, with many patients achieving weight gain, but mortality remained substantial. System-level barriers, such as insurance coverage and access constraints, were not reported in the literature but were prominent in our 2 cases.

CONCLUSIONS: In older adults, AN is rare in population samples but severe when clinically detected. The review highlights diagnostic complexity, medical risk, limited psychotherapy/medication detail, and systems barriers central to consultation-liaison practice. Consultation-liaison psychiatrists play a key role in identifying and coordinating treatment for this complex population.