Citations

Objective To evaluate the efficacy of cytokine‐directed therapies in VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory somatic) syndrome using previously proposed treatment response criteria. Methods All patients with genetically confirmed VEXAS syndrome who received targeted therapies with JAK inhibitors (JAKi), tumor necrosis factor α inhibitors (TNFαi), or interleukin‐1 (IL‐1) or IL‐6 inhibitors were identified. Clinical and biochemical data were recorded for patients at time of targeted therapy initiation, and at 3‐, 6‐, and 12‐month follow‐up time points. Treatment response was labeled as complete response (CR; normalization of C‐reactive protein [CRP], prednisone <10 mg/day, and resolution of disease activity), partial response (PR; >50% improvement in CRP, >50% prednisone dose reduction, improvement or resolution of disease features), treatment failure (TF; worsening CRP, increasing prednisone, worsening of disease features), or no response (not meeting criteria for CR, PR, or TF). Results Overall, 52 patients received an IL‐1i, IL‐6i, or JAKi therapy. At six‐month follow‐up, 3 of 19 IL‐6i patients experienced CR, 4 of 19 experienced PR, and 7 of 19 experienced TF. 2 of 17 patients receiving JAKi experienced CR, 3 of 17 experienced PR, and 6 of 17 experienced TF. No patients receiving IL‐1i or TNFαi experienced CR, and only 1 of 5 IL‐1i patients experienced PR. Among those still receiving biologic therapy at 12 months, only 1 of 11 receiving IL‐6i and 0 of 7 receiving JAKi experienced CR. Conclusion IL‐6i and JAKi therapies demonstrated limited, unsustained efficacy for management of VEXAS syndrome. IL‐1i and TNFαi therapies were not efficacious. Useful application of previously reported treatment response criteria was demonstrated, but future incorporation of hematologic parameters may be beneficial.

ABSTRACT Background Mobility functional status is inconsistently recorded in electronic health records. Recent advances in Large Language Models (LLMs) enable automated extraction of functional information from unstructured clinical notes. Leveraging a validated functional LLM with high performance in mobility extraction, we aimed to study the association between LLM‐derived mobility functional status and clinical outcomes, including emergency department (ED) visits, hospitalizations, and mortality. Methods Individuals aged 60 years and older enrolled in the Mayo Clinic Study of Aging, with documented clinical notes in 2022 were included. Individuals without any identifiable functional information were excluded. The LLM‐derived mobility functional status categorized mobility as impaired or unimpaired, across the five mobility domains as classified by International Classification of Functioning, Disability, and Health. Clinical outcomes in 2023 were extracted from the Rochester Epidemiology Project database. Logistic regression models assessed associations between mobility impairment and outcomes, adjusted for age, sex, Elixhauser comorbidity index, and education. Results Three thousand three hundred thirty‐seven individuals were screened, of whom three hundred forty‐three had no functional information. Two thousand nine hundred ninety‐four individuals were analyzed. 79.4% had at least one mobility impairment. Higher mobility impairment is associated with older age and greater Elixhauser comorbidity. Individuals with 3 or more impairments had an increased adjusted odds of ED visits (Adjusted Odds Ratio (aOR): 2.18 (1.64, 2.90)) and hospitalizations (aOR: 2.35 (1.51, 3.65)) compared to unimpaired individuals ( p < 0.001), while mortality did not demonstrate a significant association with mobility impairment. Conclusion LLM‐derived mobility functional status assessment was associated with ED visits and hospitalization, but not with all‐cause mortality after adjustment. Prospective validation and evaluation of incremental discrimination, calibration, and clinical utility are needed before clinical implementation.

Objective The aim of this study was to compare infection‐related hospitalization risk among patients with nonrenal systemic lupus erythematosus initiating commonly used immunosuppressants. Methods We emulated a target trial using Optum Labs Data Warehouse claims to compare the risk of infection‐related hospitalization among patients initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAAs) between March 2011 and September 2023. We excluded patients with prior lupus nephritis, solid‐organ or bone marrow transplantation, or rituximab/cyclophosphamide exposure. The primary outcome was time to first infection‐related hospitalization using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. We applied inverse probability of treatment weighting to account for baseline covariates and fitted marginal structural Cox models incorporating time‐varying monthly glucocorticoid dose during follow‐up. Results Among 6,168 patients, 24‐month cumulative incidence of infection‐related hospitalization was 10% (95% confidence interval [CI] 8–12) for azathioprine, 8% (95% CI 5–10) for belimumab, 10% (95% CI 8–11) for methotrexate, and 13% (95% CI 10–15) for MPAAs. In ITT analyses, MPAAs had higher risk than belimumab (hazard ratio [HR] 1.55, 95% CI 1.07–2.25) and methotrexate (HR 1.32, 95% CI 1.04–1.68). In PP analyses, azathioprine (HR 2.04, 95% CI 1.01–4.16) and MPAAs (HR 2.27, 95% CI 1.11–4.62) had higher risk compared with belimumab. After accounting for time‐varying monthly glucocorticoid dose, between‐treatment differences were no longer significant. Conclusion Initial differences in the infection‐related hospitalization risk were attenuated after accounting for time‐varying glucocorticoid exposure. These findings highlight glucocorticoid exposure as an important factor associated with serious infection risk while recognizing that postbaseline glucocorticoid use may reflect both evolving disease activity and a pathway through which therapies influence infection risk. image

Abstract Background Evaluation of middle ear prostheses requires high-resolution imaging to assess position and structural integrity. Purpose To assess the diagnostic performance of photon-counting-detector (PCD)-CT for middle ear prosthesis imaging in cadaveric specimens. Materials and Methods Nine different middle ear prostheses were implanted in five fresh-frozen whole-head specimens, both in correct anatomic position and displaced to mimic malposition. Specimens were scanned on PCD-CT (NAEOTOM Alpha, Siemens) and energy-integrating-detector (EID)-CT (SOMATOM Force, Siemens), reconstructed at 0.2mm and 0.4mm, respectively. Eighteen cases (9 prostheses, 2 positions) per scanner were evaluated by two neuroradiologists (36 readings), blinded to scanner and position, who scored prosthesis position, reader confidence, and overall image quality. Agreement with the reference standard and between readers was compared. Results PCD-CT showed higher diagnostic confidence compared with EID-CT, while accuracy and inter-reader agreement did not demonstrate significant differences between scanners. Correct readings, PCD-CT versus EID-CT: lateral contact, 31/36 (86.1%; 95% CI: 58.3%-94.4%) vs. 29/36 (80.6%; 55.6%-91.7%), p = 0.500; medial contact, 30/36 (83.3%; 55.6%-94.4%) vs. 26/36 (72.2%; 50.0%-83.3%), p = 0.250. PCD-CT identified all cases of complete contact loss (score 3), while EID-CT missed one reading per contact. Inter-reader agreement may be higher with PCD-CT vs EID-CT (lateral: κw: 0.804 [0.578-0.941] vs. 0.571 [0.302-0.778], p = 0.250; medial: 0.684 [0.191-0.934] vs. 0.481 [0.024-0.835], p = 0.250). Reader confidence was significantly higher with PCD-CT; mean paired differences for Readers 1 and 2 were 9.4 (1.8-17.1; Holm-adjusted p = 0.019) and 23.1 points (13.4-32.7; p &lt; 0.001) for lateral contact, and 16.4 (10.0-22.8; p &lt; 0.001) and 17.8 points (6.8-28.8; p = 0.007) for medial contact. Readers preferred PCD-CT image quality in 16/18 (88.9%; 65.3%-98.6%) and 17/18 cases (94.4%; 72.7%-99.9%), respectively. Conclusion PCD-CT was associated with significantly higher reader confidence and preferred image quality, without significant differences in diagnostic accuracy or inter-reader agreement. These findings suggest PCD-CT is a promising modality for postoperative middle ear evaluations that warrants further investigations.

Abstract Objective. Four-dimensional CT (4DCT) enables visualization of dynamic wrist joint pathology but may be compromised by motion artifacts. Deep learning (DL)-assisted motion correction has the potential to enhance wrist 4DCT quality, but model development is hindered by scarce training data. To address this, we developed a model-based motion simulation framework that generated realistic 4DCT data with paired static ground truth images to demonstrate wrist motion correction using a physics-informed DL model trained with simulated data. Approach. Wrist motion was simulated by synchronizing rotational and translational movements of carpal bones and connective tissues. Elastic deformation guided by analytically-derived motion vector fields was applied to static wrist scans at neutral positions to create artifact-free images at multiple angular positions. Virtual motion-corrupted 4DCT images were produced via forward projection and reconstruction with synchronized gantry and wrist motion. Experimental data from 4DCT cadaver scans were collected to validate simulation quality. Low-intensity region score (LIRS), positivity, and entropy were used to assess simulated motion artifacts. A physics-informed motion correction network was adapted exclusively using simulated training data and subsequently deployed on simulated, real cadaveric, and in vivo 4DCT scans. LIRS and structural similarity index (SSIM) were used to evaluate motion correction quality. Wilcoxon signed-rank tests were conducted ( α = 0.05). Results. The simulation method created realistic motion artifacts compared to real scan reference ( p > 0.05). Motion artifacts were effectively mitigated across testing cases demonstrating generalizability. In simulated scans, LIRS improved from 0.55 ± 0.12–0.75 ± 0.04 and SSIM from 0.87 ± 0.08–0.95 ± 0.03 at bone regions (each p < 0.01). In experimental cadaveric scans, LIRS improved from 0.05 ± 0.01–0.31 ± 0.17 in marker regions and from 0.58 ± 0.19–0.77 ± 0.14 in bone regions (each p < 0.01). Significance. Our simulation method facilitates training DL-assisted motion correction algorithms by providing high-quality training data, effectively supporting 4DCT image quality enhancement.

Objective Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population‐based SLE registries, meta‐analyses were performed estimating age‐specific incidence of SLE by sex, race, and ethnicity. Methods The CDC network of SLE registries includes five state‐based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002‐2018. Registries provided age‐specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person‐years, stratified by sex, race, and ethnicity for the meta‐analyses. Results Incidence rates among women were highest for those aged 30‐39 (12.7, 95%CI: 9.5‐16.8), while rates among men were highest for those aged 60‐69 (2.1, 95%CI: 1.3‐3.4). Black women aged 20‐39 had the highest SLE incidence rates (23.6, 95%CI: 20.7‐26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8‐15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4‐15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30‐39 years. Conclusions This study provides comprehensive sex‐ and race‐specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

Background: Telogen effluvium (TE) is one of the most common forms of nonscarring alopecia. TE typically presents as sudden diffuse shedding of hair, and generally occurs 3–4 months after a triggering event such as physiological or psychological stress, certain medications, or hormonal changes. Despite the high prevalence of TE, no standardized clinical guidelines for the management of this condition currently exist. Objective: To address the lack of standard clinical guidelines for the management of TE, a multidisciplinary panel of dermatologists, dermatology advanced practice providers, and primary care providers convened to evaluate current evidence related to the treatment of TE. Methods: The primary research team, composed of 13 individuals, completed a comprehensive literature review of TE treatment. Then an expert panel conducted 2 rounds of article review, assessing each article based on the Strength of Recommendation Taxonomy (SORT) criteria and formulating consensus statements based on this data. An expert panel of 20 clinicians then evaluated the statements utilizing a structured eDelphi consensus process. Results: A total of 18 consensus statements regarding treatment recommendations for TE were reviewed by the expert panel. Of these, 3 statements addressed acute TE, while 15 focused on chronic TE. The panel evaluated each statement through open forum discussion, followed by voting and modification using the eDelphi methodology. Ultimately, 16 statements reached consensus following 2 rounds of the eDelphi survey. Conclusion: The self-limiting nature of acute TE warrants patient education, but no specific therapies were found to improve outcomes compared with placebo. While there is a gap in quality research regarding chronic TE treatment, current evidence suggests that topical minoxidil, vitamin D supplementation, and platelet-rich plasma may provide benefit in chronic TE based on individual clinical judgement.

Background Despite advances in cervical cancer screening, cervical cancer rates have been increasing in the last decade. Hispanic women have higher cervical cancer incidence and mortality rates compared to non-Hispanic women in the United States. These disparities are primarily due to language barriers experienced in this Spanish-preferred population. Our study aims to improve cervical cancer screening rates among Spanish-preferred patients through a Spanish-language multimedia presentation on cervical cancer screening. Methods In patients not adherent to U.S. cervical cancer screening guidelines, we conducted a non-randomized study comparing standard care in Family Medicine (FM) to standard care plus a multimedia presentation with Spanish voiceover intervention in Internal Medicine (IM). We evaluated whether baseline characteristics differed between the two study arms using the Wilcoxon rank sum test and either the Chi-Square test or Fisher’s exact test. For the primary goal, we examined whether there was a difference in screening scheduling rates between the intervention and standard care groups using the Chi-Square test. Using descriptive statistics, we investigated whether there was a difference in characteristics for those who scheduled screening and those who did not. Results We had 52 patients in IM and 58 in FM, differing in age and insurance status, with median ages of 45.5 and 40.0, and percent insured of 65.4% and 82.8%. Post-study, 25.0% (13/52) in IM and 15.5% (9/58) in FM scheduled cervical screening appointments, which was not significantly different, p=0.21. Patients who scheduled screening had higher rates of insurance coverage, at 95.5% compared to 69.3%. Conclusion No statistically significant difference in scheduling rates among Spanish-preferred patients was observed in this study. Further efforts should include larger samples and randomization.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.