Publications

STUDY OBJECTIVE: To evaluate differences in the likelihood of endometriosis or adenomyosis diagnosis across genetically-defined ancestry groups (African, Admixed American, East Asian, European, and South Asian), and to determine whether social vulnerability and access to surgery influence diagnostic practices in a diverse urban population.

SETTING: Penn Medicine BioBank, a clinical and genomic biorepository.

PATIENTS: Female patients aged 18 to 51 enrolled from 2008 to 2020 and followed through March 2024.

INTERVENTIONS: Population diversity was characterized using genotyping data from peripheral blood samples. Genetic ancestry was inferred through principal component analysis and clustering with reference populations. Sociocultural factors were assessed as distinct covariates rather than conflated with racial/ethnic identity. Social vulnerability indices (socioeconomic status, family/household factors, and housing/transportation access) were defined by Census tract of the patient's residence. Endometriosis and adenomyosis were identified using International Classification of Diseases-9/10 codes, validated by chart review. Logistic regressions were adjusted for age, body mass index, social vulnerability, and interaction terms.

MEASUREMENTS AND MAIN RESULTS: Among 9258 patients, 357 (3.9%) were diagnosed with endometriosis and 464 (5.0%) with adenomyosis. When all diagnostic routes were considered (surgical, imaging, and clinical), the likelihood of endometriosis did not differ by ancestry group. However, the odds of a surgical diagnosis by laparoscopy was significantly lower for patients of African ancestry, compared with European (adjusted OR: 0.57, 95% CI: 0.38-0.85). Socioeconomic vulnerability strongly modified this association: African-ancestry patients with the highest socioeconomic vulnerability had the lowest odds of receiving an endometriosis diagnosis (aOR: 0.29, 0.14-0.61), including surgically confirmed diagnosis (aOR: 0.31, 0.12-0.80), relative to those of European ancestry with lowest vulnerability. By contrast, patients of African ancestry had higher odds of adenomyosis (aOR: 2.88, 2.16-3.85), including cases confirmed by hysterectomy (aOR: 3.44, 2.21-5.36).

CONCLUSION: Diagnostic disparities in endometriosis and adenomyosis were most pronounced at the intersection of ancestry and socioeconomic vulnerability, highlighting the need to address social determinants and barriers to equitable care.

Newborn screening (NBS) for X-linked adrenoleukodystrophy (ALD) enables early identification of boys at risk for adrenal insufficiency (AI) and cerebral ALD (CALD). However, NBS frequently identifies ABCD1 variants of uncertain significance (VUS), which are associated with only borderline-elevated C26:0-lysophosphatidylcholine (LPC(26:0)) levels. Traditional American College of Medical Genetics and Genomics (ACMG) pathogenicity classification does not account for age-dependent penetrance or the broader phenotypic spectrum, complicating risk assessment and clinical management. Through the Grey Zone Project, we developed a risk-stratification framework using a receiver operating characteristic (ROC)-based approach prioritizing 95% sensitivity. This framework incorporates biochemical and longitudinal clinical data from 1627 control subjects and 196 confirmed ALD patients. Three pediatric risk categories were defined: "no ALD" (<110 nmol/L LPC(26:0)), "lower-risk AI/CALD" (110-177 nmol/L), and "at-risk AI/CALD" (>177 nmol/L). When applied to 108 samples carrying 51 unique ABCD1 VUSs, 26 variants were reclassified as "no ALD," 15 as "lower-risk AI/CALD," and 10 as "at-risk AI/CALD." The framework reclassifies ABCD1 variants based on biochemical risk profiles, reducing false-positive referrals, avoiding unnecessary MRI surveillance, and alleviating parental anxiety by identifying children who are unlikely to develop childhood-onset disease. Integrating biochemical thresholds with genetic and longitudinal clinical data improves the specificity of NBS without compromising its sensitivity. Providing systematic feedback on false-positive cases to screening laboratories will further refine cut-offs. This framework provides a scalable, evidence-based model for interpreting variants and enabling personalized follow-up in ALD and other disorders with a variable age of onset.

Background The management of incidental adnexal lesions encountered at CT depends on the diagnosis, but little evidence supports CT diagnosis of most adnexal lesion types. Purpose To evaluate the interreader agreement and CT diagnosis of incidentally discovered adnexal lesions. Materials and Methods This institutional review board-approved, multi-institutional, multireader retrospective study conducted from January 1, 2022, to June 30, 2023, included patients who had malignant ovarian lesions with metastases (n = 8) and without metastases (n = 8), simple cysts (n = 6), dermoids (n = 9), hydrosalpinx (n = 5), benign cystadenomas and/or cystadenofibromas (n = 10), hemorrhagic cysts (n = 8), endometriomas (n = 6), ovarian fibromas (n = 5), leiomyomas (n = 5), and peritoneal inclusion cysts (n = 5) detected at CT. Nine members of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease-Focused Panel, blinded to the final diagnosis, independently reviewed the CT images and used the American College of Radiology white paper to determine the most likely diagnosis. A 2 × 2 factorial random-effects model was used to calculate the mean adjusted accuracy and disparity among the readers. Interreader agreement was calculated using a Gwet AC1 test. Results In total, 75 patients (mean age, 50 years ± 16 [SD]) were included. The mean adjusted accuracy and interreader agreement were highest for dermoids (99% and 0.97, respectively), malignant ovarian lesions with metastases (94% and 0.90), and simple cysts (86% and 0.64). The mean adjusted accuracy for all other lesion types was less than 72%, with fair to moderate interreader agreement. Overall, readers more accurately diagnosed malignant lesions (82%) than benign lesions (52%) (P < .001). Readers recorded a benign diagnosis when a malignant lesion was present 28% of the time (20 of 72) (P < .001) when there were no metastases. Conclusion Readers' mean adjusted accuracy was greatest for dermoids, malignant ovarian lesions with metastases, and simple cysts at CT, with substantial to almost perfect interreader agreement; all other lesions were challenging, and a substantial number of malignant ovarian lesions were misdiagnosed as benign. © RSNA, 2026.

Thrombosis drives substantial global mortality across atrial fibrillation, venous thromboembolism, and atherosclerosis. However, clinical scores treat risk as a static variable and omit evolving comorbidities, functional biomarkers, anatomy, and treatment exposure, leading to misclassification and preventable events. This statement advances a unified scientific agenda for patient-specific digital twins that dynamically integrate multimodal longitudinal data with mechanistic insight to predict thrombogenesis risks. We position these digital twins as hybrid models anchored in physics and data-driven algorithms that can simulate disease progression and therapy. The goal of this approach is to refine stroke and bleeding estimation beyond current clinical rules. Continuous updating from imaging data, laboratory test results, wearables, and electronic health records supports dynamic risk trajectories and adaptive care pathways, facilitating continuous risk reassessment. This statement analyzes gaps in data quality, calibration, validation, and uncertainty quantification that presently limit the clinical translation of this technology. Research priorities are then proposed for multiscale thrombosis modelling, physics-informed learning, probabilistic forecasting, and regulatory-compliant data stewardship. Finally, we outline translation to in silico trials, regulatory alignment, and hospital workflows that link predictions to decisions. By articulating shared challenges across thrombosis-driven diseases and reframing risk as a time-varying measurable quantity, this statement lays a foundation for developing digital twin approaches that support a shift from population heuristics towards precise, timely thrombosis care. These advances are essential for translating digital twin technology from research to clinical practice, enabling dynamic risk prediction and personalized anticoagulation therapy.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related presence of expanded somatic clones secondary to leukemogenic driver mutations and is associated with cardiovascular (CV) disease and mortality. We sought to evaluate relationships between CHIP with cardiometabolic diseases and incident outcomes in high-risk individuals.

METHODS: CHIP genotyping was performed in 8469 individuals referred for cardiac catheterization at Duke University (CATHGEN study) to identify variants present at a variant allele fraction (VAF) ≥2%. Associations were tested among any CHIP variant, large CHIP clones (VAF > 10%) and individual CHIP genes with prevalent cardiometabolic traits. Cox proportional hazard models tested CHIP associations with time-to-overall mortality and Fine-Gray analyses tested CHIP associations with incident cardiovascular outcomes.

RESULTS: We identified 463 CHIP variants in 427 individuals (5.0%) of which 268 (3.2%) harbored large CHIP clones. CHIP and large CHIP were associated with lower odds of obesity (OR 0.79 [95% CI 0.65-0.98], p = 0.03; OR 0.76 [95% CI 0.57-0.99], p = 0.04, respectively). CHIP was associated with prevalent heart failure (HF, OR 1.25 [95% CI 1.01-1.55], p = 0.04; especially for non-DNMT3A CHIP (OR 1.38 [95% CI 1.04-1.82], p = 0.02). CHIP was also associated with incident events: Non-DNMT3A CHIP was associated with increased risk of time-to-HF hospitalization (HR 1.29 [95% CI 1.02-1.63], p = 0.03).

CONCLUSIONS: In high-risk individuals referred for cardiac catheterization, large CHIP and non-DNTM3A CHIP were associated with obesity, prevalent HF, incident CV events. These findings strengthen the importance of CHIP as a biomarker for CV disease and highlight the contributing risk of large CHIP clones and non-DNMT3A CHIP variants.

Triple-negative breast cancers (TNBCs) lack targeted therapeutics that can inhibit their growth and progression. The long intergenic noncoding RNA LINC01133 promotes TNBC pathogenesis by increasing the abundance of proline-rich protein 5 (PRR5), an mTORC2 component that activates the kinase AKT in a PI3K-independent, mTORC2-dependent manner. Here, however, we found that TNBC cell proliferation was incompletely sensitive to AKT inhibitors alone because PRR5 also stimulated the mitogen-activated protein kinase (MAPK) cascade in an mTORC2-dependent manner. PRR5 associated with and prevented the ubiquitin-dependent proteasomal degradation of IQGAP1, an adaptor protein that promotes activation of the MAP kinase ERK. ERK signaling was essential for LINC01133-mediated TNBC proliferation in two- and three-dimensional cultures, and ERK inhibitors synergized with AKT blockade to suppress LINC01133-induced TNBC cell growth. Furthermore, PRR5 abundance was particularly enriched and correlated with that of phosphorylated ERK in samples from patients with TNBC. Our results highlight cross-talk between mTORC2 and ERK signaling downstream of LINC01133 and PRR5 that may be therapeutically targeted to treat TNBC.

PURPOSE OF REVIEW: We evaluate the converging evidence positioning lithium as a systemic modulator of bone and brain health through shared molecular pathways. This review examines the molecular basis, preclinical data, and clinical observations suggesting that lithium-long established as first-line therapy for bipolar disorder-may simultaneously protect against osteoporosis and neurodegeneration as two clinical conditions increasingly recognized to share biological substrates.

RECENT FINDINGS: Lithium inhibits glycogen synthase kinase-3β (GSK-3β), stabilizes β-catenin, and activates Wnt signaling in neurons and osteoblasts, while also modulating calcium-inositol homeostasis and suppressing NF-κB-mediated inflammation. Large observational studies report lower dementia incidence and reduced fracture risk in long-term lithium users, together with increases in bone mineral density. Declining brain lithium concentrations in patients with Alzheimer's disease raise the hypothesis that lithium may act as an essential micronutrient rather than solely a pharmacological agent. Bidirectional brain-bone crosstalk involving osteocalcin signaling and sclerostin transport across the blood-brain barrier provides a mechanistic basis for these pleiotropic effects. Lithium offers a unique paradigm for understanding and potentially treating age-related decline in multiple organ systems at subclinical dosage and concentration. However, observational study limitations, optimal dose uncertainties, and toxicity related to long-term usage concerns necessitate rigorous randomized controlled trials before broader clinical recommendations can be made. Future research should focus on optimizing formulation and patient selection to realize lithium's dual protective potential for bone and brain while minimizing risk.

BACKGROUND AND OBJECTIVES: Wikipedia has become a widely consulted source for health-related information, including transfusion medicine, by both healthcare professionals and the general public. However, the accuracy and completeness of transfusion-related content on this platform remain understudied. So, we aimed to systematically evaluate the current state and quality of transfusion medicine-related content available on Wikipedia.

MATERIALS AND METHODS: The Wikipedia Subgroup of the Clinical Transfusion Working Party of the International Society of Blood Transfusion (ISBT) conducted a cross-sectional analysis of transfusion medicine-related Wikipedia articles up to 31 December 2024. Articles were identified using the search terms 'Transfusion', 'Blood Components', 'Blood Groups' and related topics. Data extracted and analysed included article metadata, content metrics, visibility indicators and editorial activity.

RESULTS: A total of 190 Wikipedia pages related to transfusion medicine were identified, with an additional 14 domain-specific webpages. The most common categories were blood groups (15.3%), blood components (13.7%) and clinical transfusion medicine (11.6%). Nearly 50% of pages were created between 2006 and 2010. Only 21.6% of pages were classified as complete, while 48.4% remained in the development phase.

CONCLUSION: This study uncovers significant gaps in transfusion medicine content on Wikipedia, with many articles found to be incomplete or poorly maintained. These findings present a clear opportunity for healthcare professionals, particularly members of the ISBT Clinical Transfusion Working Party's Wikipedia Subgroup, to enhance the quality, accuracy and accessibility of transfusion-related information through coordinated, collaborative editing efforts.