Citations

Abstract Purpose Large language models (LLMs) have proven performance for certain diagnostic tasks; however, limited studies have evaluated their consistency in recommending appropriate medication regimens for a given diagnosis. Medication management is a complex task that requires synthesis of drug formulation and complete order instructions for safe use. Here, the performance of GPT-4o, an LLM available with OpenAI’s ChatGPT, was tested on 3 medication management tasks. Methods GPT-4o performance was tested on 3 medication tasks: identifying available formulations for a given generic drug name, identifying drug-drug interactions (DDIs) for a given medication regimen, and preparing a medication order for a given generic drug name. For each experiment, the model’s raw text response was captured exactly as returned and evaluated using clinician evaluation in addition to standard LLM metrics, including Term Frequency-Inverse Document Frequency (TF-IDF) vectors, normalized Levenshtein similarity, and Recall-Oriented Understudy for Gisting Evaluation (ROUGE-1/ROUGE-L) F1 score between each response and its reference string. Results For the first task of drug-formulation matching, GPT-4o had 49% accuracy for generic medications being matched to all available formulations, with an average of 1.23 omissions per medication and 1.14 hallucinations per medication. For the second task of drug-drug interaction identification, the accuracy was 54.7% for identifying the DDI pair. For the third task, GPT-4o generated order sentences containing no medication or abbreviation errors in 65.8% of the cases. Conclusion Model performance for basic medication tasks was consistently poor. This evaluation highlights the need for domain-specific training through clinician-annotated datasets and a comprehensive evaluation framework for benchmarking performance.

Abstract Background At hospice enrollment, patients are asked preferences regarding antibiotic use. Limited evidence on how these medications impact survival makes it difficult for clinicians to offer clear guidance. To support decision-making and antimicrobial stewardship, we assessed the association between antibiotic use and survival in outpatient hospice patients. Methods The association between antibiotic use and survival was evaluated using a time-dependent Cox proportional hazards model, adjusted for age, sex, Charlson Comorbidity Index, and hospice-qualifying conditions (HQCs). The cohort included patients enrolled in a large health system’s outpatient hospice program between June 20, 2017, and January 1, 2023. Results Among 6169 patients with an HQC, 1233 received at least one antimicrobial prescription during the study period. The median time from hospice enrollment to first prescription was 16 days (IQR 3-83). Antimicrobial prescribing patterns varied by HQC category. In time-dependent Cox models, antibiotic use was associated with increased hazard of death (aHR 1.47; 95% confidence interval [CI], 1.37–1.57).Stratified analyses showed the strongest association with increased mortality in patients with cancer HQCs (aHR 1.67; 95% CI, 1.50–1.87) and a survival benefit in those with infectious HQCs (aHR 0.60; 95% CI, 0.40–0.89). Discussion Physicians, patients, and families often overestimate the benefits of antibiotics near the end of life. The observed increase in mortality shortly after antibiotic initiation suggests that symptoms prompting antibiotic use may reflect the dying process rather than treatable infection. Knowledge of the limited role of antibiotics in prolonging life in hospice settings may improve decision-making and enhance the quality of end-of-life care.

Abstract To characterize invasive neuromodulation for insular drug‐resistant epilepsy, we retrospectively evaluated 22 patients treated with responsive neurostimulation (RNS; n = 14) or chronic subthreshold stimulation (CSS; n = 8). Stereoelectroencephalography was performed in 20 cases (91%). Median baseline seizure frequency was 10.5/month. Forty‐one percent had prior epilepsy surgery. At year 3, median seizure reduction (MSR) was 83% ( p = .01, Wilcoxon signed‐rank test), with a responder rate (RR) of 77%; MSR was 92% for CSS and 75% for RNS. There were no significant differences in MSR ( p ≥ .4) or RR ( p > .9) when comparing RNS versus CSS. Three patients achieved seizure freedom by year 3. Patients undergoing combined insular–thalamic stimulation ( n = 5) demonstrated an MSR of 84%, 86%, and 88% at 1, 2, and 3 years; seizure reduction in thalamocortical versus cortical‐only stimulation was not different ( p ≥ .1). Parasagittal lead trajectories achieved closer insular proximity than transopercular trajectories ( p < .0001, Mann–Whitney U ‐test). Median charge density at last follow‐up was 1.3 μC/cm 2 . There were no acute surgical complications and all stimulation‐related side effects resolved with programming adjustments. This study expands the limited literature on insular neuromodulation by demonstrating effectiveness of RNS and CSS, suggesting potential benefit from combined thalamocortical targeting, and defining parasagittal trajectories as a surgical approach for optimal lead proximity.

ABSTRACT Purpose This study assesses the association between colorectal cancer (CRC) screening and a validated, housing-based measure of individual-level socioeconomic status (SES, called HOUSES hereafter) within rural communities and determines whether HOUSES-integrated geospatial analysis can be used to tailor interventions. Methods We used CRC screening data from a subset of Mayo Clinic Midwest patients living in cities without ready access to routine care in the Mayo Clinic Health System in 2019 to represent rural communities. At the individual level, we assessed the association between CRC screening rates and the HOUSES index, adjusting for age, sex, race/ethnicity, comorbidity, distance from home address to clinic, and area deprivation index, using a multilevel mixed-effects logistic regression model. Additionally, we conducted geospatial analysis to examine the correlation between hotspots of 1) lower CRC screening rates and 2) lower SES of the subject population (HOUSES quartile 1). Findings Among 34,489 individuals (median age 64.0 years, 52.4% female), those with the lowest SES (HOUSES Q1) had 37% lower odds of being CRC screening adherent than those with the highest SES (HOUSES Q4) (adj. OR [95% CI]: 0.63 [0.58-0.69]). In the 14 identified HOUSES Q1 hotspots, there was a significant correlation in counts of HOUSES Q1 and low CRC screening (correlation coefficient=0.81). Conclusion Lower SES was significantly associated with lower CRC screening among rural populations. HOUSES-enabled geospatial analysis identified geographic hotspots with lower CRC screening rates for targeted interventions to address disparities in CRC screening in rural communities. HOUSES may be a useful digital tool for cancer preventive care and research.

Study Design: Retrospective. Objective: To examine the long-term perioperative changes in lumbar bone quality, paraspinal muscle size and fat content, and facet degeneration after hemipelvectomy (HP) and hip disarticulation (HD). Summary of Background Data: Emerging evidence shows that transfemoral (TFA) and transtibial (TTA) amputations may accelerate lumbar modic changes and precipitate axial back pain. TFA and TTA amputation studies demonstrate that the severity of postamputation lower back pain is associated with the amputation type (TFA > TTA) and the degree of alteration in lumbopelvic kinematics. Methods: All patients who underwent HP or HD for malignancy or infection at an academic center between 2003 and 2022 were retrospectively identified. Preoperative to postoperative changes in multifidus, erector spinae, quadratus lumborum, and psoas cross-sectional area (CSA), and Hounsfield units (HU) were calculated on CT for the amputated and contralateral side at the level of the L3–4 disc space. Paired univariate analysis was utilized to compare preoperative and postoperative outcomes. Results: A total of 16 patients (8 HP, 8 HD) met the inclusion/exclusion criteria. The preoperative to postoperative changes in HUs in the L1, L3, and L5 vertebral bodies were −27.0 ( P =0.004), −51.5 ( P =0.002), and −48.1 ( P =0.001), respectively. The decrease in L1 HU was greater for prosthesis nonusers (user: −16.50, nonuser: −51.32, P =0.021). L5–S1 segment facet degeneration increased postoperatively ( P =0.030, n=7 progressed). There were significant preoperative to postoperative changes in psoas CSA (preop: 1063.4, postop: 586.5, P =0.005) and psoas HU (preop: 50.95, postop: 33.55, P <0.001) on the amputated but not the contralateral side. Conclusion: Hind-quarter amputations were associated with decreased lumbar bone quality, progression of facet degeneration, and loss of amputated side psoas muscle tone. Daily prosthesis use was moderately protective for lumbar bone quality following amputation. HP but not HD was associated with postoperative loss of amputated side quadratus lumborum tone. Level of Evidence: Level III.

Purpose Radioligand therapy (RLT) with [ 177 Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [ 177 Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [ 177 Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC. Methods Clinical and imaging data of patients who underwent at least two cycles of [ 177 Lu] Lu-PSMA-617, followed by a second course of treatment with [ 177 Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively. Results A total of 589 patients underwent [ 177 Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 years (range: 63.7–95.2), and the median follow-up was 73.3 months (95% CI, 35.7–77.2 months) after the initial treatment and 21.7 months (95% CI, 16.9–26.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2–6). Following the first course of RLT, 15 patients (75%, 15/20) had exhibited a &gt;50% decline in PSA levels, including 9 who achieved a &gt;90% decrease. Additionally, 12 patients (60%, 12/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3/20) patients had stable disease, and 5 (25%, 5/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1–6), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2–48.9 months; range, 10.7–58.8 months). A PSA decline of ≥50% was observed in 9 out of 20 patients (45%, 9/20). An imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1–17.9 months), and the median rPFS was 8.2 months (95% CI, 3.3–17.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%–94.4%) and 53.7% at 24 months (95% CI, 28.3%–73.7%). Grade 2 renal toxicity was observed in one patient (5%, 1/20). Three patients (15%, 3/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period. Conclusion In our cohort, retreatment with [¹ 77 Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.

The intestinal epithelium is exposed to diverse combinations of microbiota-derived compounds; however, the mechanisms by which the host integrates these signals remain poorly defined. Studying two highly abundant microbial metabolites, we identified the purine metabolite hypoxanthine as an effector metabolite that directly drives signaling and the short-chain fatty acid butyrate as a regulatory metabolite that conditions host responsiveness. Specifically, hypoxanthine activates the adenosine A1 receptor–TRPC4 axis in enterochromaffin (EC) cells, triggering calcium influx and serotonin release resulting in accelerated gastrointestinal transit locally and increased platelet activation systemically. In contrast, butyrate epigenetically upregulates specific G protein–coupled receptors and ion channels to enhance response to hypoxanthine and the neurotransmitters norepinephrine and dopamine. These findings define a cooperative signaling framework and highlight the role of EC cells as a distinct epithelial signaling hub that senses and integrates microbial metabolite signals to drive physiological responses. Our findings provide a mechanistic foundation for therapeutic strategies that leverage combinatorial microbial signaling.