Citations

Background: The timing of coronary artery bypass grafting (CABG) in patients with non-ST-elevation myocardial infarction (NSTEMI) may critically impact clinical outcomes, yet the ideal surgical window remains unclear. We aimed to evaluate the association between time-to-CABG and in-hospital outcomes among NSTEMI admissions undergoing CABG. Methods: This retrospective cohort study utilized the US National Inpatient Sample database from 2017 to 2021 to evaluate the association between time-to-CABG and key in-hospital outcomes, including mortality, cardiac arrest, cardiogenic shock, ischemic stroke, acute kidney injury, and blood transfusion rates, while assessing length of stay (LOS) and hospital charges exclusively among survivors. Adult admissions with principal diagnosis of NSTEMI who underwent CABG without prior interhospital transfer were grouped by the calendar day of CABG from admission (0, 1, 2, 3, 4, 5, 6, and ≥7). Multivariate regression models were used to assess the outcomes across these eight groups. Results: Of 142,200 included admissions, same-day CABG (hospital day 0) was associated with the highest rates of in-hospital mortality, cardiac arrest, cardiogenic shock, and ischemic stroke. The adjusted odds of mortality, cardiac arrest, and cardiogenic shock were lower among admissions undergoing CABG between days 2 and 5. Likewise, the adjusted odds of ischemic stroke were lowest when CABG occurred on days 2 to 4. The odds of AKI increased when CABG was delayed beyond day 6, whereas blood transfusion rates showed no statistically significant association with time-to-CABG. Among survivors, LOS and hospital charges progressively increased with delayed CABGs. Conclusions: Among NSTEMI admissions undergoing CABG, CABG performed on hospital days 2 to 4 was associated with lower adjusted odds of several adverse in-hospital outcomes compared with same-day CABG. Further prospective studies are needed to validate these results and guide clinical decision-making.

Introduction Individuals with inborn errors of immunity (IEI) are increasingly reaching reproductive age, yet guidance on fertility preservation, genetic counseling, medication adjustments in pregnancy and breastfeeding, monitoring for complications, and multidisciplinary coordination is lacking. This joint effort between two committees of the Clinical Immunology Society (CIS), the Women of the Clinical Immunology Society (WCIS) and the Adult Immune Deficiency Committee (AID) survey aimed to characterize current reproductive care practices for IEI patients. Methods A survey was disseminated to 809 CIS members. The response rate was 6.43% (52 respondents). The 24-item questionnaire addressed management of pregnancy in IEI, medications adjustment, participation in hematopoietic stem cell transplant (HSCT) care and fertility preservation, and maternal/neonatal outcomes. Results Because survey items were optional, the number of respondents varies by question. Forty-two participants completed core items: 64% (27/42) allergists/immunologists, 71% (30/42) practicing at academic centers, and 48% (20/42) with >50% immunology-focused practices. Most respondents (78%, 41/52) currently or previously cared for pregnant/planning IEI patients. Preconception counseling was common (90%, 37/41), yet only 2% (1/41) have access to a formal reproductive multidisciplinary team. Among clinicians involved in HSCT care, 45% (13/29) referred patients for fertility preservation. More than half, 52% (22/42), observed reduced fertility in IEI patients, and 56% (20/36) observed adverse maternal outcomes. Medication management varied: 61% (24/39) discontinued known teratogenic medications, and 64% (25/39) adjusted dosing during pregnancy. Regarding immunoglobulin replacement therapy, 79% adjusted dosing based on IgG levels and 42% increased dosing by trimester. Conclusions This CIS survey reveals practice variability and notable gaps in reproductive health support for individuals with IEIs. Due to the relatively low response rate, generalizability across providers and practice settings is challenging. However, the results of this survey suggest that although most clinicians provide preconception counseling and manage IgG and immunomodulatory therapy during pregnancy, formal multidisciplinary structures are rare. High rates of reported fertility concerns and maternal complications underscore the need for enhanced collaboration with obstetrics/gynecology and the development of structured, evidence-based, multidisciplinary guidelines for reproductive care in IEI. Tabular data are included as downloadable supplement files.

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.

Retrieval-augmented generation (RAG) is rapidly emerging as a transformative paradigm for large language models (LLMs), especially in high-stakes domains like oncology that demand precision, factual grounding, and up-to-date knowledge. By pairing LLMs with external knowledge repositories, RAG systems explicitly ground model outputs in relevant retrieved documents, helping to reduce hallucinations and ensure responses reflect current evidence. In oncology, where clinical knowledge evolves continually with new research and drug approvals, RAG offers a way to integrate the latest data (e.g., trial results, guidelines, genomic databases) into decision-making. This review synthesizes the technical foundations of RAG, including its architecture and key components, and examines current applications in oncology such as clinical decision support, patient education, radiology reporting, pathology analysis, and genomics-driven precision medicine. We highlight recent studies that demonstrate RAG’s potential—for instance, improving treatment recommendations by incorporating genetic profiles and literature, and enhancing diagnostic accuracy by integrating guidelines. We also discuss emerging developments like multimodal RAG (combining text with imaging or other data), ensemble model approaches, and new explainability tools that trace model outputs to sources. Finally, we critically analyze the limitations and challenges of deploying RAG in healthcare, including computational costs, retrieval errors, noise or conflicts in retrieved information, and ethical and regulatory considerations. While RAG-based systems show promise in augmenting oncologists’ expertise with timely knowledge, careful implementation, high-quality curation of knowledge bases, and human oversight will be crucial for safe and effective adoption in clinical practice.

INTRODUCTION: Nosocomial infections (NIs) in cirrhosis are associated with high mortality but could be preventable. Logistic regression (LR) models have failed to identify high-risk patients. We aimed to develop machine learning (ML) models to predict NI. METHODS: The CLEARED consortium consists of prospectively enrolled cirrhosis inpatients from >120 centers. Using day-of-admission clinical data, 3 ML approaches (random forest [RF], extreme gradient boosting, and neural networks [NNs]) were used to predict NI. Data were split 80:20 for training and testing stratified by the outcome. Models were compared using area under the receiver operating characteristic curve (AUC). RESULTS: In total, 8,263 patients (55.90 ± 13.34 years; 64.1% men) from 127 centers in 37 countries were included. NI developed in 869 (10.5%), a median of 6 (4–11) days of postadmission. Major NIs were respiratory (29.6%) and urinary tract infection (15.7%), and spontaneous bacterial peritonitis (13.5%). NIs occurred more frequently in patients from low/low-middle income countries and those with severe liver disease, alcohol etiology, and admission infections. NIs were associated with inpatient mortality (31.9% vs 8.1%, P < 0.001) and liver transplantation (4.8% vs 1.9%, P < 0.001). Although the RF model (AUC 0.69) showed good calibration (Brier score 0.09), outperforming extreme gradient boosting, neural network, and LR models (AUC 0.66 for all; LR comparison P = 0.043), no model achieved AUC ≥0.80 for clinical utility. At 10% predicted probability threshold, the RF model demonstrated only 75.4% sensitivity, 52.9% specificity, and 15.9% positive predictive value (PPV). DISCUSSION: NIs cannot be accurately predicted from day-of-admission data using ML models, even in a large, prospective, global cirrhosis cohort. Every hospitalized patient with cirrhosis should receive protocolized infection control measures.

53BP1 nuclear bodies are dynamic structures with properties resembling biomolecular condensates, but the molecular determinants that govern 53BP1 higher-order assembly at DNA double-strand breaks (DSBs) remain to be established. Here, we show that 53BP1 condensation is stimulated by phosphatidylinositol 3-phosphate (PI(3)P) in vitro through a highly specific interaction with its C-terminal tandem BRCT domain (tBRCT). Consequently, mutational inactivation of the 53BP1 tBRCT domain compromised PI(3)P binding and suppressed 53BP1 optodroplet formation in vivo. We further show that rapid 53BP1 clustering following DNA damage precedes its stable assembly on DSB-flanking chromatin, requires its tBRCT, and is suppressed by sequestration of nuclear PI(3)P. Taken together, our findings identify PI(3)P binding as a mechanism that promotes the formation and maturation of 53BP1 condensate-like assemblies on damaged chromatin.

The 6th edition of the WHO Classification of Breast Tumours introduces both major and minor changes based on recent advances in our understanding of breast biology, developments in diagnostic modalities, identification of specific molecular targets and new treatment regimens necessitating modifications to pathology reporting and tumour biomarker categorisation. This review summarises the main changes that strive towards a classification of global relevance. In invasive carcinoma, predictive factors increasingly inform modern breast cancer treatment. The 6th edition provides an update on HER2 reporting categories following the DESTINY‐Breast 04 and 06 trials. Terminologies used to classify invasive tumours are clarified, with the term ‘variant’ now reserved for molecular/genetic alterations. Invasive lobular carcinoma (ILC) with extracellular mucin is recognised as a new diagnostic entity with prognostic implications. The diagnosis of mucinous carcinoma (MC) is reserved for mucin secreting carcinomas with grade 1 or 2 morphology and a favourable biomarker profile. The diagnosis of malignant phyllodes tumours requires only four of the original five adverse histological criteria. Classification of neuroendocrine tumours (NETs) is revised, recognising that the unified model, promoted in the 5th edition, is difficult to apply to the breast. New approaches to the classification of adenomyoepithelioma are discussed but the 5th edition system is broadly retained. A new section on ‘Small Diagnostic Samples’ outlines the merits of non‐operative biopsy diagnosis, the B coding system and the importance of multidisciplinary review. Changes to diagnostic practice and the emerging role of artificial intelligence, with advantages and challenges, are discussed in a new section on ‘Digital Pathology’.

Background The PREPARE trial (Pragmatic Randomized trial Evaluating Pre-operative Alcohol skin solutions in Fractured Extremities), published in February 2024, demonstrated that 0.7% iodine povacrylex in 74% isopropyl alcohol reduced surgical site infections in patients with closed fractures compared with chlorhexidine gluconate in 70% isopropyl alcohol. Prior studies have shown that the translation of clinical trial findings into routine clinical practice and surgical procedures frequently takes longer than a decade, and strategies to accelerate implementation in orthopaedic surgery remain poorly defined. Engaging in a multifaceted implementation strategy with minimal barriers to entry for providers may be able to reduce this time to widespread adoption. Questions/purposes (1) Can the low-cost single-center dissemination efforts of the PREPARE trial results change antiseptic usage? (2) If a true practice change occurs, can the change be sustained over time without additional dissemination efforts? (3) Does the adoption of new evidence vary between fellowship-trained orthopaedic trauma surgeons and orthopaedic trauma surgeons who are not fellowship-trained? (4) What is the economic impact of a practice change to iodine povacrylex on hospital purchasing costs? Methods This was a retrospective, historically controlled comparative study of patients who underwent operative treatment of an extremity fracture at a single, urban, Level I academic trauma center before and after a dissemination effort aimed at increasing PREPARE trial awareness. A multifaceted dissemination strategy consisting of surgeon and nursing education, posted reminders, and supply chain support was implemented at the study site in February 2024. Patients were analyzed across three time periods: before dissemination (January 2020 to January 2024), during the transition (February 2024), and after dissemination (March 2024 to July 2025). An electronic medical record query identified patients with operative fracture management procedural codes who had a recorded antiseptic skin prep in the surgical flow sheet between January 2020 and July 2025. A total of 4822 patients were identified, and 222 duplicate entries were excluded, leaving 4600 patients for analysis (3351 before dissemination, 49 transitional, and 1200 after dissemination). To validate the completeness of our electronic health record query, we performed manual random sampling of monthly operative case logs, confirming that this query strategy successfully identified all patients with the relevant Current Procedural Terminology codes (that is, there were no exclusions for lack of antiseptic documentation). There were no differences in patient demographics, including sex, ethnicity, open fractures, or the distribution of upper and lower extremity fractures. Choice of surgical skin antiseptic was compared before and after dissemination using a log-binomial model. Results Dissemination efforts changed antiseptic use patterns with an immediate increase in iodine povacrylex use from 0.8% (27 of 3351) before intervention to 86% (1033 of 1200) after intervention (OR 765 [95% confidence interval 488 to 1197]; p < 0.001). This high level of use remained stable throughout the 17-month postintervention period without any additional dissemination efforts (p = 0.20 for trend). Adoption was higher among fellowship-trained trauma surgeons (94.8% increase) compared with surgeons without trauma fellowship training (34.7% increase). Hospital antiseptic product purchasing data, which reflect usage and restocking and were used as a secondary metric of practice change, also demonstrated an increase in iodine povacrylex demand and decline in chlorhexidine demand. Conclusion A targeted and multifaceted dissemination strategy led to rapid adoption of iodine povacrylex for use as the preferred surgical skin antisepsis in fracture surgery at our institution, which was sustained over the 17-month postintervention period. This finding contrasts with a historically slow uptake of surgical trial evidence into clinical practice. Pragmatic, low-cost approaches such as surgeon leadership, team-based multidisciplinary education, workflow reminders, and supply chain readiness may help to accelerate translation of evidence into orthopaedic practice. Future studies should evaluate the long-term sustainability of practice changes, surgical site infection outcomes, and generalizability across institutions. Level of Evidence Level III, therapeutic study.

Background/Aims: Infections with drug-resistant organisms (DROs) are associated with poor outcomes in cirrhosis. Rifaximin, widely used for hepatic encephalopathy (HE), could promote cross-resistance, but data regarding clinical impact are conflicting. Aim: Determine predictors of DROs in a global cirrhosis inpatient cohort focusing on preadmission rifaximin use.Methods: From the global CLEARED consortium, we focused on cirrhosis inpatients with infections on/during admission. Clinical/demographic/medication, especially rifaximin details were recorded. The primary outcome was DRO development. Multivariable regression for DRO including clinical, medications, and country income was performed.Results: 2,949 infected inpatients (55.3 years, 62.9% male) were included. 12.2% of all and 24.4% of culture-positive infections developed DROs; these patients had higher HE (39 vs. 31%, <i>P</i>=0.003), hepatorenal syndrome (25 vs. 19%, <i>P</i>=0.006), lactulose (55 vs. 47%, <i>P</i>=0.008) and rifaximin use (34 vs. 27%, <i>P</i>=0.006) on crude comparisons but country-income distributions were similar. 29.7% were on pre-admission rifaximin, mostly HE-related; they had more advanced cirrhosis and from low/low-middle-income countries. Daptomycin was used in 1.5%, linked with DROs (5.0 vs. 1.0%, <i>P</i><0.0001) without a difference in rifaximin use (1.4 vs.1.7%, <i>P</i>=0.61). On adjusted analysis, MELD-Na (1.03, 95% CI 1.02–1.04, <i>P</i><0.001) increased, whereas male sex (0.73, 95% CI 0.58–0.92, <i>P</i>=0.008) and hepatitis-B (0.65, 95% CI 0.45–0.92, <i>P</i>=0.020) decreased DRO. Rifaximin was not associated with DROs overall (OR 1.07, 95% CI 0.80–1.43, <i>P</i>=0.65) or within income strata (high: 1.07, 95% CI 0.59–1.92, <i>P</i>=0.82, upper-middle: 1.18, 95% CI 0.74–1.85, <i>P</i>=0.49, low/low-middle: 1.04, 95% CI 0.60–1.81, <i>P</i>=0.90) despite sensitivity analyses.Conclusions: In this large global cohort of hospitalized patients with cirrhosis and infections, 12% developed infections involving DROs. 30% had pre-admission rifaximin use which was not linked with daptomycin use or with DRO development on adjusted analysis overall or across country income groups.