Publications

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.

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.

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.

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.

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.

OBJECTIVES: This study aimed to assess the risk of venous thromboembolism (VTE) among obese and nonobese females aged 10 to 44 years prescribed hormonal therapy (HT) and compare VTE rates between different HT types in a large national database.

METHODS: A retrospective cohort study was conducted using TriNETX data, which includes electronic health records and pharmaceutical claims from 81 million patients across 56 US tertiary care hospitals. Females prescribed HT between 2000 and 2022 were stratified by body mass index. VTE incidence was identified using International Classification of Diseases, Ninth/Tenth Revision, codes and anticoagulant prescriptions. Propensity score matching controlled for confounders.

RESULTS: Of 4,020,467 females, 34% (1,370,481) were obese. VTE incidence was higher in obese HT users (0.99%) than nonobese users (0.51%; P < .01). Obese users of levonorgestrel + ethinyl estradiol (EE) had a VTE rate of 0.55% vs 0.33% in nonobese users (P = .01, relative risk [RR] = 1.63). Similarly, obese users of norethindrone + EE (0.44% vs 0.24%; P < .01; RR = 1.8) and norgestimate + EE (0.44% vs 0.22%; P < .01; RR = 1.97) had higher VTE rates. No significant differences were found for progesterone-only HT users.

CONCLUSION: In this large study comparing rates of VTE among obese and nonobese females on HT, a significantly higher risk of VTE was observed among obese females using certain HTs, particularly EE with levonorgestrel, norethindrone, and norgestimate. These results highlight the importance of considering obesity as a key risk factor when prescribing HT, particularly for females with higher body mass index.

PURPOSE: To report a rare case of endocrine mucin-producing sweat gland carcinoma (EMPSGC) of the eyelid, initially misdiagnosed as a chalazion.

OBSERVATIONS: A 76-year-old South-Asian male presented with a 9-month history of a painless left upper eyelid lesion. Initial ophthalmic assessment suggested presence of a chalazion that did not resolve with medical management. Examination revealed a 5.5 × 5.5 mm mass at the central left eyelid margin. The lesion transilluminated and extended over the eyelid margin, with splayed lashes but no madarosis. Histopathological examination demonstrated cribriforming glandular epithelium with extracellular mucin and synaptophysin expression, confirming EMPSGC with associated mucinous carcinoma. The patient underwent successful Mohs micrographic surgery with oculoplastic reconstruction and with no evidence of recurrence at five-month follow-up.

CONCLUSION AND IMPORTANCE: EMPSGC is an uncommon, low-grade adnexal neoplasm, often under-recognized due to its benign appearance. This case highlights the importance of considering EMPSGC in the differential diagnosis of persistent eyelid lesions, particularly those unresponsive to conservative treatment. Histopathologic evaluation is critical for early recognition and appropriate management of lesions.

Men who have sex with men (MSM) with a history of childhood sexual abuse (CSA) are more likely to report crystal methamphetamine use and condomless anal intercourse (CAI) than MSM without CSA. MSM with CSA may benefit less in HIV prevention interventions due to long-term psychological effects. Data are from a pilot randomized, controlled trial testing an integrated HIV risk reduction and behavioral activation counseling intervention vs standard of care among MSM with methamphetamine use disorder, which showed effects at reducing CAI. We conducted a secondary analysis (N = 38) to preliminarily assess whether CSA moderated the intervention effects on the two primary outcomes: CAI acts with men whose HIV serostatus was either positive or unknown (1) overall (CAI overall) and (2) while under the influence of methamphetamine (CAI with methamphetamine). At the immediate postintervention assessment, the interaction term between CSA and intervention arm was not statistically significant for either outcome, indicating no moderation effect. However, at the 3-month postintervention assessment, the interaction term was significant for both outcomes. At this time point, for those without CSA, there was a significantly lower number of CAI acts in the intervention condition vs the comparison condition for both outcomes. For those with CSA, however, there was no significant difference between the intervention and comparison conditions for CAI overall, although for the outcome CAI with methamphetamine, the intervention condition had higher levels. Future HIV prevention interventions among MSM with methamphetamine use disorder should consider screening for CSA and addressing CSA-related psychological distress, which may potentially preserve intervention effects.

This review explores the dual regenerative and antimicrobial properties of platelet- and marrow-derived biologics, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), autologous protein solutions, and plasma fractions. These biologics, widely used in regeneration and tissue repair, offer multiplex bioactivity through growth factors, cytokines, and cellular components that promote healing while reducing infection risk. PRP and BMAC demonstrate significant regenerative effects in musculoskeletal conditions, wound healing, and cartilage repair, with platelets and leukocytes contributing antimicrobial peptides and immune modulation for more indirect regenerative mechanisms. Preparation methods, patient factors, and lack of standardization impact clinical outcomes and efficacy. While promising for reducing reliance on chronic pain medications and improving function, these therapies face limitations including inconsistent preparation and utilization protocols, limited long-term safety data, and regulatory challenges. Here, we review the need for consensus-building, standardized procedures, and robust research to optimize clinical integration and realize the full potential of biologic regenerative therapies in pain medicine.

Inflammatory bowel disease, encompassing ulcerative colitis and Crohn's disease, is characterised by chronic immune-mediated inflammation and variable treatment response. Loss of drug efficacy due to underexposure, pharmacokinetic variability, and immunogenicity remains a key challenge. Therapeutic drug monitoring, using drug levels and anti-drug antibody measurements, is an important strategy for optimising the treatment of inflammatory bowel disease. It helps ensure adequate dosing and can distinguish between pharmacokinetic and mechanistic drug failure. Most evidence pertains to infliximab and adalimumab. Multiple factors influence drug pharmacokinetics, affecting both target drug levels and the doses required to achieve them. These include inflammatory burden, bodyweight, age, disease phenotype, and route of administration, all of which are important considerations for individualising treatment in inflammatory bowel disease. This narrative review explores how special clinical situations-acute severe ulcerative colitis, perianal fistulising Crohn's disease, hypoalbuminaemia, extremes of body composition, pregnancy, paediatrics, and advanced age-alter drug pharmacokinetics and influence the utility and interpretation of therapeutic drug monitoring in inflammatory bowel disease.