Citations

Abstract Rationale Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic progressive pulmonary fibrosis and high mortality. Genetic markers, summarized into a polygenic risk score (PRS), associate with IPF in well-phenotyped research cohorts. Objectives To evaluate the performance of the PRS using real-world data from routinely captured electronic healthcare records. Methods We conducted an observational study evaluating the association of a PRS for IPF with electronic healthcare record diagnosis of IPF as well as lung transplant-free survival in four independent cohorts; the Mass General Brigham Biobank (MGBB), Mayo Clinic Biobank (MCBB), Mayo Clinic Tapestry Cohort (Tapestry), and U.K. Biobank (UKBB). We used multivariable logistic regression and multivariable Cox proportional hazards models adjusting for age, gender, and principal components of ancestry. The cohorts then underwent fixed and random effects meta-analysis. Measurements and Main Results Of 37,709; 44,195; 43,202; and 447,422 participants from MGBB, MCBB, Tapestry and UKBB respectively, 1,015 (2.7%) 2,879 (6.5%), 1,310 (3.0%), and 2,742 (0.6%) participants had an IPF diagnosis. Meta-analysis demonstrated a high-risk PRS associated with IPF diagnosis, OR 2.88 (95%CI 2.41-3.44) compared to all other individuals. A high-risk PRS also associated with the composite endpoint of mortality or lung transplant among those with an IPF diagnosis, HR 1.23(95%CI 1.11-1.35) compared to all other individuals. Conclusions A PRS can identify those at risk for an IPF diagnosis and mortality in biobank-scale data, which may have implications for clinical decisions. Further work is necessary to evaluate the utility of adding genetics in clinical settings.

ABSTRACT Background and Objectives NCCN guidelines recommend right hemicolectomy (RHC) for appendiceal neuroendocrine tumors (aNETs) > 2 cm and observation for < 1 cm. However, optimal surgical management of 1–2 cm tumors remains controversial. This study compared long‐term survival and recurrence between patients undergoing RHC versus appendectomy (APY) for 1–2 cm aNETs. Methods Patients with pathologically confirmed 1–2 cm aNETs treated at three Mayo Clinic sites (1972–2024) were included. Primary outcomes were recurrence and all‐cause mortality after resection. Associations with lymph node (LN) metastasis were assessed in patients with lymphadenectomy. Results Sixty‐five patients were identified: 29 (45%) underwent APY, 35 (54%) RHC, and one ileocecectomy. Median age at diagnosis was 39 years; 71% were female and 94% white. LN positivity was 15.2% for tumors with nodes examined. Tumor size > 1.5 cm, stage T3/T4, and lymphovascular invasion were not associated with nodal metastasis. No survival differences were observed between APY and RHC. LN positivity did not impact survival. No recurrences occurred during a median follow‐up of 6.25 years (IQR 2.44–12.63). Conclusions Among patients with 1–2 cm aNETs, RHC conferred no survival benefit over APY. Absence of recurrence and the limited prognostic value of nodal disease suggest APY alone may suffice for this population.

Background: Automated discharge instructions are increasingly used to support post-discharge communication, patient education, and nursing follow-up, yet the current state remains unidentified. This systematic review explores the types of automated discharge instructions used and their effectiveness in enhancing patient engagement and reducing readmission, emergency department visits and reoperation rates. Methods: A systematic search was conducted on 15 April 2025, using Embase, PubMed, Scopus, Web of Science, and CINAHL, following PRISMA guidelines. Inclusion criteria required peer-reviewed original research evaluating the utilization of automated patient discharge instructions following hospital admission or surgical stay. Exclusion criteria included correspondence, reviews, educational materials, not peer-reviewed, retracted reports, not retrievable, and no English translation. Risk of bias was assessed independently using NIH, JBI, ROB-2, and ROBINS-I tools. Two investigators independently conducted the screening, extraction, and synthesis of results using Endnote and Microsoft Excel. Results: Of the 1252 records identified, 13 studies were selected for analysis. There was a total of 34,386 patients across a diverse range of healthcare settings and clinical contexts. The average sample size per study was approximately 4912, with study samples ranging from 16 to 13,188 patients. The modalities of discharge instructions included automated phone calls (23.1%) and/or text messages (53.8%), as well as printed out auto-generated summaries (15.4%). Patient engagement was generally high, with automated phone calls showing the most consistent interaction, with completion rates ranging from 44% to 56%, often prompting clinical follow-up. SMS tools demonstrated strong scalability and response rates up to 87%. Two studies reported on hospital readmission outcomes and only a single study reported on emergency department revisit rates, while none assessed reoperation outcomes. Among those reporting readmission, automated phone calls and SMS were associated with lower or proxy-reduced readmission rates. Included studies had low to moderate levels of bias. Conclusions: While evidence on clinical outcomes such as readmissions, emergency department revisits, and reoperations remains limited and inconclusive, automated discharge tools—particularly phone calls and SMS—consistently demonstrated high patient engagement. Automated discharge tools show promise for supporting transitional care, discharge education, and post-discharge monitoring, highlighting the future role of automated tools in nursing workflows to support follow-up, escalation, and continuity of care.

(1) Background: Large language models (LLMs) show promise in healthcare but are constrained by hallucinations, static knowledge, and limited domain specificity. Fine-tuning (FT) and retrieval-augmented generation (RAG) offer complementary solutions, with FT embedding domain reasoning and RAG enabling dynamic, up-to-date knowledge access. Hybrid FT + RAG frameworks have been proposed to improve factual accuracy and clinical reliability. This scoping review synthesizes current evidence on such hybrids in healthcare AI. (2) Methods: The search across PubMed, IEEE Xplore, Google Scholar, and Embase identified studies implementing explicit FT + RAG hybrids in healthcare or biomedical tasks. Eligible studies reported empirical evaluations of LLM performance or behavior. Data were extracted on base models, FT strategies, RAG architectures, applications, and performance outcomes. (3) Results: Seven studies met inclusion criteria. FT + RAG systems consistently outperformed FT-only or RAG-only approaches across QA, clinical summarization, report generation, and decision support tasks. Parameter-efficient FT methods (e.g., LoRA) were common, while RAG implementations varied (dense, hybrid, hierarchical, multimodal, federated). Reported benefits included improved accuracy, reduced hallucination, and greater clinician preference and feasibility in protected settings. (4) Conclusions: FT + RAG frameworks represent a promising direction for clinically grounded healthcare AI, combining domain-specific reasoning with transparent, up-to-date retrieval. Future work should prioritize standardized evaluation, workflow integration, and governance to enable safe deployment.

Background: Generative AI and synthetic media have enabled realistic human Embodied Conversational Agents (ECAs) or avatars. A subset of this technology replicates faces and voices to create realistic likenesses. When combined with avatars, these methods enable the creation of “digital twins” of physicians, offering patients scalable, 24/7 clinical communication outside the immediate clinical environment. This study evaluated surgical patient perceptions of an AI-generated surgeon avatar for postoperative education. Methods: We conducted a pilot feasibility study with 30 plastic surgery patients at Mayo Clinic, USA (July–August 2025). A bespoke interactive surgeon avatar was developed in Python using the HeyGen IV model to reproduce the surgeon’s likeness. Patients interacted with the avatar through natural voice queries, which were mapped to predetermined, pre-recorded video responses covering ten common postoperative topics. Patient perceptions were assessed using validated scales of usability, engagement, trust, eeriness, and realism, supplemented by qualitative feedback. Results: The avatar system reliably answered 297 of 300 patient queries (99%). Usability was excellent (mean System Usability Scale score = 87.7 ± 11.5) and engagement high (mean 4.27 ± 0.23). Trust was the highest-rated domain, with all participants (100%) finding the avatar trustworthy and its information believable. Eeriness was minimal (mean = 1.57 ± 0.48), and 96.7% found the avatar visually pleasing. Most participants (86.6%) recognized the avatar as their surgeon, although many still identified it as artificial; voice resemblance was less convincing (70%). Interestingly, participants with prior exposure to deepfakes demonstrated consistently higher acceptance, rating usability, trust, and engagement 5–10% higher than those without prior exposure. Qualitative feedback highlighted clarity, efficiency, and convenience, while noting limitations in realism and conversational scope. Conclusions: The AI-generated physician avatar achieved high patient acceptance without triggering uncanny valley effects. Transparency about the synthetic nature of the technology enhanced, rather than diminished, trust. Familiarity with the physician and institutional credibility likely played a key role in the high trust scores observed. When implemented transparently and with appropriate safeguards, synthetic physician avatars may offer a scalable solution for postoperative education while preserving trust in clinical relationships.

Background: During postoperative recovery, patients and their caregivers often lack crucial information, leading to numerous repetitive inquiries that burden healthcare providers. Traditional discharge materials, including paper handouts and patient portals, are often static, overwhelming, or underutilized, leading to patient overwhelm and contributing to unnecessary ER visits and overall healthcare overutilization. Conversational chatbots offer a solution, but Natural Language Processing (NLP) systems are often inflexible and limited in understanding, while powerful Large Language Models (LLMs) are prone to generating “hallucinations”. Objective: To combine the deterministic framework of traditional NLP with the probabilistic capabilities of LLMs, we developed the AI Virtual Assistant (AIVA) Platform. This system utilizes a retrieval-augmented generation (RAG) architecture, integrating Gemini 2.0 Flash with a medically verified knowledge base via Google Vertex AI, to safely deliver dynamic, patient-facing postoperative guidance grounded in validated clinical content. Methods: The AIVA Platform was evaluated through 750 simulated patient interactions derived from 250 unique postoperative queries across 20 high-frequency recovery domains. Three blinded physician reviewers assessed formal system performance, evaluating classification metrics (accuracy, precision, recall, F1-score), relevance (SSI Index), completeness, and consistency (5-point Likert scale). Safety guardrails were tested with 120 out-of-scope queries and 30 emergency escalation scenarios. Additionally, groundedness, fluency, and readability were assessed using automated LLM metrics. Results: The system achieved 98.4% classification accuracy (precision 1.0, recall 0.98, F1-score 0.9899). Physician reviews showed high completeness (4.83/5), consistency (4.49/5), and relevance (SSI Index 2.68/3). Safety guardrails successfully identified 100% of out-of-scope and escalation scenarios. Groundedness evaluations demonstrated strong context precision (0.951), recall (0.910), and faithfulness (0.956), with 95.6% verification agreement. While fluency and semantic alignment were high (BERTScore F1 0.9013, ROUGE-1 0.8377), readability was 11th-grade level (Flesch–Kincaid 46.34). Conclusion: The simulated testing demonstrated strong technical accuracy, safety, and clinical relevance in simulated postoperative care. Its architecture effectively balances flexibility and safety, addressing key limitations of standalone NLP and LLMs. While readability remains a challenge, these findings establish a solid foundation, demonstrating readiness for clinical trials and real-world testing within surgical care pathways.

Retrieval-augmented generation (RAG) quality depends on how source documents are segmented before indexing; fixed-length chunks can split concepts or add noise, reducing precision. We evaluated whether proposition, semantic, and adaptive chunking improve accuracy and relevance for safer clinical decision support. Using a curated domain knowledge base with Gemini 1.0 Pro, we built four otherwise identical RAG pipelines that differed only in the chunking strategy: adaptive length, proposition, semantic, and a fixed token-dependent baseline. Thirty common postoperative rhinoplasty questions were submitted to each pipeline. Outcomes included medical accuracy and clinical relevance (3-point Likert scale) and retrieval precision, recall, and F1; group differences were tested with ANOVA and Tukey post hoc analyses. Adaptive chunking achieved the highest accuracy—87% (Likert 2.37 ± 0.72) versus baseline 50% (1.63 ± 0.72; p = 0.001)—and the highest relevance (93%, 2.90 ± 0.40). Retrieval metrics were strongest with adaptive (precision 0.50, recall 0.88, F1 0.64) versus baseline (0.17, 0.40, 0.24). Proposition and semantic strategies improved all metrics relative to baseline, though less than adaptive. Aligning chunks to logical topic boundaries yielded more accurate, relevant answers without modifying the language model, offering a model-agnostic, data-source-neutral lever to enhance the safety and utility of LLM-based clinical decision support.

Importance Contemporary guidelines recommend sentinel lymph node biopsy (SLNB) for patients with melanoma with predicted risk of SLN metastasis greater than 10% and consideration of SLNB when the risk is 5% to 10%. A gene expression profile (GEP)–based test that can accurately identify patients with a low risk of SLN metastasis would refine selection for SLNB. Objective To establish the predictive capability of the combined clinicopathological factors and GEP (CP-GEP) test to identify patients with primary cutaneous melanoma who can safely forgo SLNB and to investigate the prognostic value of CP-GEP regarding the outcome in patients with cutaneous melanoma after a negative SLNB (not reported herein). Design, Setting, and Participants This prognostic study was conducted from September 2021 to June 2024 at 9 academic medical centers with experienced melanoma surgeons. Included were patients with biopsy-proven invasive cutaneous melanoma with T1 to T3 tumors and clinically negative regional LNs. All patients were deemed candidates for SLNB using standard clinical criteria. GEP was performed on formalin-fixed, paraffin-embedded tissue from the primary melanoma biopsy. Analyses were performed from December 2024 to August 2025. Intervention CP-GEP testing to determine risk of having a positive SLNB in patients with T1 to T3 cutaneous melanoma who were considered appropriate candidates for the procedure based on standard clinical parameters. Main Outcomes and Measures CP-GEP results were reported as low risk or high risk; the primary outcome measure was negative predictive value (NPV) in low-risk cases. Analyses included NPV assessment by tumor (T) subcategory, primary site, and age. Results A total of 1761 patients (median [IQR] age, 64 [53-72] years; 997 male [56.6%]) underwent SLNB (310 [17.6%] SLN positive) and had a successful CP-GEP test; GEP was successful in 97.7% of samples. A total of 651 patients (37.0%) were considered low risk by CP-GEP. Among low-risk cases, 46 (7.1%) were SLN positive, and NPV was 92.9% (95% CI, 90.7%-94.8%). High-risk cases had a 23.8% (264 of 1110) SLN-positive rate. The percentage of cases with low-risk CP-GEP declined with increasing T category (T1 = 346 of 507 [68.2%]; T2 = 295 of 897 [32.9%]; T3 = 10 of 357 [2.8%]). CP-GEP results were consistent in discriminating SLN-positive rates across primary sites, histologic subtypes, and mitotic count categories. In 2 large subsets, clinical stage IB (n = 1187) and patients 65 years and older (n = 832), 6.5% (95% CI, 4.6%-8.8%) of low-risk clinical stage IB cases and 6.6% (95% CI, 4.2%-9.7%) of all low-risk cases in patients 65 years and older were SLN positive vs 18.3% (95% CI, 15.3%-21.6%) and 20.3% (95% CI, 16.8%-24.2%) for high-risk cases, respectively. Conclusions and Relevance In this multicenter, prospective, blinded, prognostic study, the CP-GEP test reliably identified patients with melanoma with less than 10% SLN metastasis risk. SLN metastasis rates were approximately 3-fold greater for high-risk vs low-risk CP-GEP cases. In appropriately selected patients, the CP-GEP test may add value for shared patient-surgeon decision-making.

Background: Artificial Intelligence (AI)-driven Decision Support Systems (DSSs) promise improvements in diagnostic accuracy and clinical workflow efficiency, but their adoption is hindered by inadequate confidence calibration, limited transparency, and poor alignment with real-world decision processes, which limit clinician trust and lead to high override rates. Methods: We developed and validated a dynamic scoring framework to enhance trust in AI-generated diagnoses by integrating AI confidence scores, semantic similarity measures, and transparency weighting into the override decision process using 6689 cardiovascular cases from the MIMIC-III dataset. Override thresholds were calibrated and validated across varying transparency and confidence levels, with override rate as the primary acceptance measure. Results: The implementation of this framework reduced the override rate to 33.29%, with high-confidence predictions (90–99%) overridden at a rate of only 1.7%, and low-confidence predictions (70–79%) at a rate of 99.3%. Minimal transparency diagnoses had a 73.9% override rate compared to 49.3% for moderate transparency. Statistical analyses confirmed significant associations between confidence, transparency, and override rates (p < 0.001). Conclusions: These findings suggest that enhanced transparency and confidence calibration can substantially reduce override rates and promote clinician acceptance of AI diagnostics. Future work should focus on clinical validation to optimize patient safety, diagnostic accuracy, and efficiency.

Retrieval-Augmented Generation (RAG) offers a promising strategy to harness large language models (LLMs) for delivering up-to-date, accurate clinical guidance while reducing physicians’ cognitive burden, yet its effectiveness hinges on query clarity and structure. We propose an adaptive Self-Query Retrieval (SQR) framework that integrates three refinement modules—PICOT (Population, Intervention, Comparison, Outcome, Time), SPICE (Setting, Population, Intervention, Comparison, Evaluation), and Iterative Query Refinement (IQR)—to automatically restructure and iteratively enhance clinical questions until they meet predefined retrieval-quality thresholds. Implemented on Gemini-1.0 Pro, we benchmarked SQR using thirty postoperative rhinoplasty queries, evaluating responses for accuracy and relevance on a three-point Likert scale and for retrieval quality via precision, recall, and F1 score; statistical significance was assessed by one-way ANOVA with Tukey post-hoc testing. The full SQR pipeline achieved 87% accuracy (Likert 2.4 ± 0.7) and 100% relevance (Likert 3.0 ± 0.0), significantly outperforming a non-refined RAG baseline (50% accuracy, 80% relevance; p < 0.01 and p = 0.03). Precision, recall, and F1 rose from 0.17, 0.39 and 0.24 to 0.53, 1.00, and 0.70, respectively, while PICOT-only and SPICE-only variants yielded intermediate improvements. These findings demonstrate that automated structuring and iterative enhancement of queries via SQR substantially elevate LLM-based clinical decision support, and its model-agnostic architecture enables rapid adaptation across specialties, data sources, and LLM platforms.