Publications by Year: 2025

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.

BACKGROUND: The integration of generative artificial intelligence (genAI) tools into clinical practice and health care systems is reshaping modern healthcare, introducing technology as an active third participant in the evolving physician-patient-technology relationship. As these tools begin to play more prominent roles, understanding physicians' perspectives is essential for guiding their ethical and effective use.

OBJECTIVE: This survey examined physicians' use of genAI and their views on its potential impact on empathy, the physician-patient relationship, and psychobiological mechanisms such as the placebo and nocebo effects.

METHODS: A cross-sectional survey was distributed to 2,444 physicians at a major academic pediatric hospital in Boston (October 2024-February 2025). The survey included items on genAI use, perceptions of its clinical and relational impact, and associated concerns. A total of 319 (13%) completed responses were analyzed using descriptive and inferential statistics.

RESULTS: Within 2 years of the public release, 65.2% of respondents had used genAI tools, most commonly for administrative tasks like writing emails (55.8%) and documentation (31.3%). Use was more common among younger physicians and men. A majority believed genAI could improve patient care (60.7%) and increase time for direct interaction (65.7%). However, views were more divided regarding its ability to support empathetic care or influence placebo effects, with many physicians expressing neutrality or uncertainty. Notably, 50.8% agreed that genAI-human interactions could increase patient anxiety, indicating concern about potential nocebo effects. Perspectives on broader genAI adoption were mixed, with 30.6% expressing concern and 37.7% neutral.

CONCLUSION: Physicians are rapidly adopting genAI tools, primarily for administrative use, while remaining cautious about its relational and psychological implications. These findings underscore the importance of addressing ethical concerns and supporting clinicians as they navigate this evolving triadic relationship between physician, patient, and genAI.

BACKGROUND: Adherence to annual OGTT screening for cystic fibrosis-related diabetes (CFRD) is poor. In this mixed methods study we assessed the accuracy, feasibility, and acceptability of alternative approaches to glucose measurements during an OGTT.

METHODS: Standard OGTT with plasma glucose sampling at 0, 60, and 120-min was conducted in 14 youth ≥ 10 years of age with CF. A self-administered OGTT kit (Digostics, GTT@home) measuring capillary glucose and Dexcom G7 continuous glucose monitoring (CGM) were performed concomitantly with OGTT. CGM glucose values were recorded at 5-minute intervals for 20-minutes after each time point to account for lag. Plasma OGTT glucose and glucose tolerance categories [normal (NGT), impaired (IGT), indeterminate (INDET), and CFRD] were compared with these same outcomes as defined by the self-administered kit and CGM. Younden's index was used to determine the optimal CGM timepoint for categorization of glucose tolerance, and ROC curves were used to identify the optimal glucose thresholds. Participants and their parents were interviewed to understand their experience with alternative testing approaches.

RESULTS: Based on plasma glucose, participants were characterized as NGT (n = 8), IGT (n = 5), and CFRD (n = 1). Whereas the GTT@home correctly categorized glucose tolerance in 6 participants (43 %), CGM correctly categorized 13 (93 %). The CGM glucose at 125 min was identified as the timepoint at which the measured glucose yielded maximum discrimination for all categories of glucose tolerance (AUC for NGT = 0.979, IGT = 0.867, CFRD = 1.0). A CGM glucose threshold of 154 mg/dL demonstrated 100 % sensitivity and 87.5 % specificity for identifying NGT; for IGT a threshold of 182 mg/dL exhibited 80 % sensitivity and 88.9 % specificity. Parent-child dyads valued convenience during OGTT screening, but expressed concerns about glucose measurement accuracy and performing medical procedures in the home.

CONCLUSIONS: CGM glucose values during OGTT may offer an accurate assessment of glucose tolerance categories, though this approach may require further refinement for patient acceptability.

BACKGROUND: Despite documented relationships between multiple forms of stigma and health outcomes, limited research has examined the effects of both HIV and alcohol stigmas on objectively measured alcohol use. Research is needed to better understand relationships between stigma and health outcomes to inform intervention efforts that reduce stigma.

METHODS: Participants (N = 60) who met criteria for unhealthy alcohol use and suboptimal HIV medication adherence were recruited from two public HIV care sites in South Africa. Internalized alcohol stigma, enacted alcohol stigma, internalized HIV stigma and phosphatidylethanol [PEth] levels, an alcohol use biomarker, were assessed at baseline, and three- and six-months post-baseline. Participants were randomized to a peer-delivered behavioral intervention or enhanced treatment as usual (facilitated referral to a co-located substance use treatment program). A cross-lagged panel structural equation model with three mediators was used to test lagged effects of stigma on PEth outcomes and whether stigma mediated the effects of the peer intervention.

RESULTS: Significant lagged effects were identified such that higher levels of enacted alcohol stigma and internalized HIV stigma at baseline separately predicted higher PEth levels at three-month follow-up. Higher levels of internalized alcohol stigma predicted higher PEth levels at six-month follow-up. No significant intervention effects were found on stigma (ps > 0.05). Stigma did not mediate the effect of the intervention.

CONCLUSIONS: Findings suggest that higher HIV and alcohol stigma predict greater alcohol use. Future research should explore how stigma reduction strategies can be incorporated into peer-delivered interventions and evaluate the effects of reducing stigma on health outcomes.Trial Registration: ClinicalTrials.gov NCT03529409.

BACKGROUND: Following the launch of ChatGPT in November 2022, interest in large language model-powered chatbots has soared with increasing focus on the clinical potential of these tools. Building on a previous survey conducted in 2024, we sought to gauge general practitioners' (GPs) adoption of this new generation of chatbots to assist with any aspect of clinical practice in the UK.

METHODS: An online survey was disseminated in January 2025 to a stratified convenience sample of GPs registered with the clinician marketing platform Doctors.net.uk. The research was conducted as part of a scheduled monthly 'omnibus survey,' designed to achieve a fixed sample size of 1000 participants.

RESULTS: Of the 1005 respondents, 50% respondents were men, 54% were 46 years or older. 25% reported using generative artificial intelligence (GenAI) tools in clinical practice; of these, 35% reported using these tools to generate documentation after patient appointments, 27% to suggest a differential diagnosis, 24% for treatment options, and 24% for referrals. Of the 249 GPs who used generative AI for clinical tasks, 71% said that, in general, these tools reduced work burdens. In the last 12 months, 85% reported that their employer had not encouraged them to use GenAI tools, but only 3% said their employer had prohibited them from using GenAI tools in their work; 95% reported they had no professional training in using GenAI tools in their work.

CONCLUSIONS: This survey suggests that doctors' use of GenAI in clinical practice may be growing in the UK. Findings suggest that UK GPs may benefit from these tools, especially for administrative tasks and clinical reasoning support, and after adopting them, most users reported a decrease in work burdens. Continued absence of reported training remains a concern.