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Importance Delirium is a state of acute confusion characterized by deficits in attention that occurs commonly during hospitalization and is associated with adverse outcomes; however, the association of delirium with longitudinal cognitive trajectories is not fully understood. Objective To evaluate the association of delirium during hospitalization with subsequent development of mild cognitive impairment (MCI), dementia, and longitudinal cognitive trajectories. Design, Setting, and Participants This cohort study used data from participants with hospitalizations in the Mayo Clinic Study of Aging (MCSA) from October 2004 to December 2023. The MCSA is a prospective, population-based longitudinal study of cognitive aging among residents of Olmsted County, Minnesota. Of participants enrolled in the MCSA between 2004 and 2023, individuals who experienced 1 or more hospitalization prior to their last MCSA encounter were included in this study. Participants with dementia at MCSA enrollment or prior to first hospitalization were excluded. Follow-up continued until development of MCI or dementia, last MCSA visit, or the end of the study. Exposure Delirium was identified using a validated natural language processing algorithm applied to clinical notes from hospitalizations, associated emergency department visits, and follow-up within 30 days after hospitalization. Delirium status was modeled as a time-dependent exposure. Main Outcomes and Measures Incident MCI and dementia were assigned through MCSA expert consensus evaluations, including neuropsychological testing performed every 15 months. Association between delirium and development of MCI or dementia was assessed using Cox proportional hazards regression, adjusted for patient age, sex, level of education, and apolipoprotein E (APOE) ε4 allele carrier status; cognitive trajectories were assessed with linear mixed-effects models. Results Of 7030 participants enrolled in the MCSA, 3542 individuals experienced 1 or more hospitalization prior to their last MCSA encounter and were included, and 41 participants with dementia at enrollment or prior to first hospitalization were excluded. The cohort included 3501 participants with at least 1 hospitalization. Median (IQR) age was 74.1 (66.6-80.9) years, 1676 participants (47.9%) were female, median (IQR) level of education was 14 (12-16) years, and 910 participants (26.0%) were APOE ε4 carriers. During a median (IQR) follow-up of 7.2 (4.1-10.4) years, 75 participants (2.1%) had delirium documented within 30 days of hospitalization. Delirium was associated with increased risk of MCI (adjusted hazard ratio [aHR], 3.67; 95% CI, 2.19-6.15) and dementia (aHR, 5.39; 95% CI, 2.94-9.85) and with accelerated decline in longitudinal cognitive testing. Conclusions and Relevance In this cohort study among adults in the MCSA, including those with unimpaired cognition at baseline, delirium during hospitalization was strongly associated with increased risk of MCI and dementia and accelerated cognitive decline in subsequent years.

Background & Aims: To evaluate safety and efficacy of FGFR1–3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements ( FGFR2 F ), mutations ( FGFR2 M ), or amplifications ( FGFR2 A ), previously treated with chemotherapy. Approach & Results: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2 F (Substudy 1) or FGFR2 M /FGFR A (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent. Conclusions: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.

Abstract Objective In 2024, the US News and World Report (USNWR)'s Best Hospitals began reporting complications following elective outpatient otolaryngology procedures in its ears, nose, and throat (ENT) ranking. However, this methodology has not been clinically adjudicated in a peer‐reviewed domain. We aimed to conduct manual health record adjudication to assess whether the USNWR methodology accurately attributes complications following elective outpatient otolaryngology procedures. Study Design Case‐cohort. Setting A case‐cohort of n = 80 elective, outpatient otolaryngology procedure/complication pairings from January 2019 to October 2023 across four academic medical centers using the 2024 USNWR otolaryngology procedure subgroups and Solventum Ambulatory Potentially Preventable Complications (AM‐PPC) software. Methods We used the AM‐PPC‐defined complication types as our standard of comparison for our clinical adjudication. Using the electronic health record, we adjudicated: (1) Was there agreement (yes/no) on complication type between our clinical adjudication and the Solventum AM‐PPC software? (2) Was the complication clinically related to, or a sequela of, the index otolaryngology procedure (yes/no)? Results The clinical adjudication agreed on complication type in 59/80 (74%) of patients, and 63/80 (79%) were judged to be clinically related to the index otolaryngology procedure. In total, 50/80 (63%) complications were adjudicated to be in agreement on both the complication type and clinical relatedness to the index procedure, while 9/80 (11%) complications did not agree with the complication type nor were clinically related to the index procedure. Conclusion Outpatient complications reported in the USNWR ENT rating lack the specificity to exclude patients whose complications are sequelae of chronic underlying conditions or related to concurrent, non‐otolaryngology procedures.

Systematic reviews of randomized controlled trials (RCTs) support evidence-based clinical advancement. Clinical trial reporting guidelines, including CONSORT, establish common data elements that support systematic synthesis of published trial outcomes. However, the rapid rise of digital health technologies presents new challenges for reporting guidelines, and substantial real-world reporting heterogeneity has been observed. Therefore, machine-assisted evaluation of reporting adherence offers a pathway for more agile information management to accommodate the diverse and disruptive nature of digital health technology-enabled RCTs. Here, we propose an accelerated retrieval-to-abstraction literature synthesis framework to conduct article screening, text and table data preprocessing, and full-text review using an unmodified pretrained large language model. We apply this methodology in two digital health technology-enabled RCT case studies evaluating adherence to technology and digital health equity guideline reporting items. Large language model performance was on par with inter-annotator agreement F1 scores (≥0.9) in both screening and information-extraction tasks. These findings support the scalability and rigor of accelerated evidence synthesis and demonstrate the importance of common reporting elements across digital health technology-enabled RCTs.

AI skill development is essential in health professions education (HPE), yet this type of faculty development is complex to design and implement. While competency frameworks and AI education programs are emerging, many faculty developers are themselves still building AI literacy and confidence, and practical guidance for how to design a faculty development program on AI that is accessible, skill-oriented, and responsive to rapid technological change remains limited. Although webinars and workshops can only do so much, a well-planned faculty development program can provide a great introduction to AI, alleviate fears, and inspire participants to keep growing and learning. Drawing on our experience designing and hosting the AAMC GEA AI Skill-Building Webinar Series and the current literature in AI, this article offers twelve practical tips for faculty developers who are creating AI-focused learning opportunities for everyone involved in HPE. These tips will help readers create robust AI skill-building sessions that move participants beyond awareness of AI and shift their perspectives toward applied, reflective, and responsible use of AI in HPE.

The immune tumor microenvironment (iTME) plays a crucial role in disease biology of plasma cell (PC) dyscrasias, but remains poorly characterized in self-identified Black individuals, a population at increased risk. Mass cytometry and scRNA-seq of 128 bone marrow aspirates revealed significant changes in immune cell composition across the disease spectrum, including shifts from naïve to effector T cells with declines in B cells, MAIT, pDCs, and increases in monocytes with disease progression. Self-identified Black patients had higher relative proportions of terminally differentiated T cells and lower monocytes in newly diagnosed and treated multiple myeloma (MM). ScRNA-seq revealed genes overexpressed in self-identified Black individuals were enriched for E2F targets and G2-M checkpoints, while reduced genes were enriched for TNF-α/NF-kB, interferon and inflammatory responses pathways. These findings were supported by genetic ancestry and validated in an independent dataset of 286 patients with MM from the MMRF Immune Atlas. Self-identified race and African genetic similarity are significantly associated with remodeling the MM iTME, with potential implications for disease biology and treatment response.

Serrated polyposis syndrome (SPS) is the most common polyposis syndrome, yet SPS often goes unrecognized. SPS diagnosis is based on clinical criteria established by the World Health Organization and includes the size, cumulative lifetime number, and location of serrated polyps throughout the colon. Individuals with SPS have an increased risk of prevalent and incident colorectal cancer (CRC). Meticulous inspection, clearing of the colon and frequent surveillance colonoscopy is recommended to decrease incident CRC. Colorectal surgery is indicated for individuals diagnosed with cancer or whose polyp burden cannot be managed endoscopically by expert endoscopists. There is no common germline pathogenic variant associated with SPS. Germline genetic testing is indicated only in individuals who meet criteria for a known hereditary syndrome in the appropriate clinical setting. First-degree relatives of patients with SPS are at heightened risk of CRC and should undergo colonoscopic screening.

Abstract Post-traumatic headache (PTH) is the most common consequence of mild traumatic brain injury (mTBI) and often resembles migraine. In 20% to 30% of migraine patients, headaches are preceded by aura, transient visual or sensory disturbances, which are caused by cortical spreading depression (CSD) that can induce headache pain. However, whether mTBI promotes the development of aura and CSD and their possible contributions to PTH remains unclear. We examined the incidence of new-onset aura in individuals with PTH who had no history of aura. Thirty-two percent (35/108) developed new aura symptoms within 60 days of injury, suggesting that mTBI can sensitize the cortex to the induction of CSD. To test this, we combined electrophysiology, neuroimaging, and behavioral assays in a mouse model of mTBI-induced PTH. After closed-head mTBI, injured mice exhibited a 160% increase in CSD induction probability (ie, lowered threshold) and became sensitized to CSD induction by brief exposure to stress, a common headache trigger. When evoked optogenetically, CSD produced prolonged periorbital and hind paw allodynia, consistent with headache-like pain. Subcutaneous onabotulinumtoxinA administered to the scalp after mTBI did not alter CSD susceptibility but completely abolished optogenetic CSD-induced allodynia. These findings suggest that mTBI elicits sensitization to CSD induction and promotes the emergence of aura in humans, likely contributing to PTH. It is important that, even after mTBI-induced sensitization, onabotulinumtoxinA decoupled CSD from pain behaviors, suggesting efficacy in treating PTH associated with aura.

Background: A growing body of research has connected electronic health record (EHR) workload to physician burnout. In orthopedic surgery, burn-out rates are rising. This study analyzed orthopedic surgeons' EHR use by sex and practice experience. Materials and Methods: EHR activity was analyzed among attending orthopedic surgeons at a single institution from May 2022 to May 2023. Demographic information included self-reported sex and practice years. Outcomes included time spent in notes, orders, clinical review, and in-basket daily; time spent outside of scheduled clinical responsibilities; volume of in-basket messages received daily; and proportion of orders with team contributions. Multivariable linear regression compared outcomes by sex and practice years. Results: A total of 105 orthopedic surgeons were included (91% male; mean 15.5 ± 9.8 practice years). Female surgeons logged 31% more time in the EHR overall (62.2 vs 47.4 minutes daily; P = .05) and on unscheduled days (10.1 additional daily minutes; P = .03), and received more messages from patients (2.4 vs 1.0 messages daily; P = .002) compared to male surgeons. Senior surgeons spent significantly less time on documentation and orders ( P ≤ .048) and on unscheduled days (3.3 less minutes daily per practice decade; P = .013), and had more support with placing orders ( P < .001). Conclusion: Female sex and fewer practice years were associated with increased EHR use. Female orthopedic surgeons tended to have higher patient message volumes, whereas junior surgeons tended to have less team support, spending more time on orders and documentation. Given known factors contributing to burnout, these findings warrant further investigation into targeted interventions to improve physician EHR use.

ABSTRACT Background Evaluating fairness in artificial intelligence (AI) is essential before clinical implementation to prevent unintended harm across diverse patient populations. This study assesses performance differences of an image-based surgical site infection (SSI) detection model across age, gender, geography, race, and skin color. Methods Model development/validation study using retrospective, multicenter data across surgical subspecialties from adults who submitted an image of their incision via the electronic health record within 30 days of their procedure between 2019-2024. Area under receiver operating curve (AUROC) was compared by age (<55 vs. ≥55 years old), gender (male vs. female), geography (Rochester, Minnesota vs. Jacksonville, Florida vs. Scottsdale, Arizona vs. regional Minnesota/Wisconsin areas), race (White/Caucasian vs. non-White/Caucasian), and skin color (Fitpatrick I-III vs. IV-VI and Monk A-E vs. F-J). Results Training data contained 13,702 images from 4,274 patients between 2019-2022 (50.1% ≥55 years old; 63.2% female; 91.6% White/Caucasian; 58.5% Rochester, 17.3% Florida, 10.5% Arizona; 96.3% light skin tone), of which 1,348 images (9.8%) had an SSI. No differences in SSI detection existed for age, gender, race, or skin color (AUROC 0.83-0.87, p>0.09), however geographical differences were significant: lowest AUROC 0.83 (95% CI 0.77-0.88) vs. highest AUROC 0.87 (95% CI 0.84-0.89, p=0.01). Temporal validation using 4,242 images from 1,353 patients between 2022-2023 showed intact fairness across subgroups (ΔAUROC ≤0.06) except geography (ΔAUROC ≤0.16). Conclusions The model behaved fairly across age, gender, race, and skin color, however geographical differences persisted. These findings have practical implications underscoring the importance of evaluating bias in clinical AI before deployment.