Citations

Alzheimer’s disease (AD) is marked by the pathological accumulation of amyloid beta-42 (Aβ42), contributing to synaptic dysfunction and neurodegeneration. While extracellular amyloid plaques are well-studied, increasing evidence highlights intracellular Aβ42 as an early and toxic driver of disease progression. In this study, we present a novel, Generative AI–based drug design approach to promote targeted degradation of Aβ42 via the ubiquitin–proteasome system (UPS), using E3 ligase–directed molecular glues. We systematically evaluated the ternary complex formation potential of Aβ42 with three E3 ligases (CRBN, VHL, and MDM2) through structure-based modeling, ADMET screening, and docking. We then developed a Ligase-Conditioned Junction Tree Variational Autoencoder (LC-JT-VAE) to generate ligase-specific small molecules, incorporating protein sequence embeddings and torsional angle-aware molecular graphs. Our results demonstrate that this generative model can produce chemically valid, novel, and target-specific molecular glues capable of facilitating Aβ42 degradation. This integrated approach offers a promising framework for designing UPS-targeted therapies for neurodegenerative diseases.

Background: Over 2.3 million liposuctions are performed annually with a complication rate of approximately 5%, including a death rate of 1 in 5000 because of blood loss. Artificial intelligence models offer potential for improving blood loss prediction and management in these procedures, analyzing extensive data to identify risk factors and accurately estimate blood loss. Methods: Data from 721 large-volume liposuction patients at 2 centers in Bogotá, Colombia, and Loja, Ecuador, between 2019 and 2023 were evaluated. Both centers followed identical perioperative protocols. The data set was split into training (621 patients) and testing (100 patients) sets. A supervised machine learning model was trained to predict blood loss. Model predictions were compared with clinical data using statistical validation metrics. Results: Most patients were women (79.2%), with median values of age of 37 years; weight, 65 kg; height, 165 cm; body mass index, 24.34 kg/m²; volemia, 3924.41 mL; infiltrated volume, 5800 mL; and aspirated volume, 3900 mL. Previous liposuction was noted in 32%. No significant differences were found between training and testing cohorts. The model achieved a mean absolute error of 22.09 mL, root mean square error of 34.13 mL, and an R ² value of 0.974, indicating high predictive accuracy and excellent model fit. Conclusions: The authors’ study has developed and validated an accurate artificial intelligence–based model to predict blood loss in large-volume liposuction, showing 94.1% accuracy. The authors’ model enhances preoperative planning and intraoperative management, potentially reducing complications and improving outcomes.

BACKGROUND: Rising health care costs necessitate a reassessment of routine preoperative practices. Despite low transfusion rates in elective colorectal operations, many hospitals continue to perform routine preoperative type and screen testing. OBJECTIVE: To assess perioperative blood transfusion rates and determine preoperative and surgical factors associated with transfusions to determine whether the routine preoperative type and screen testing are necessary for elective abdominal colorectal surgeries, particularly in the setting of minimally invasive surgery. DESIGN: Retrospective cohort study. SETTINGS: Mayo Clinic, 2019–2023. PATIENTS: Adult patients undergoing elective abdominal colorectal operations. Exclusion criteria included emergent operations and nonabdominal procedures. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was the incidence of intraoperative and immediate postoperative (≤72 hours) blood product transfusion. Secondary outcomes assessed associations between transfusion rates, surgical approach, and preoperative variables. RESULTS: Among 4652 patients, 2770 underwent minimally invasive surgery and 1882 underwent open procedures. Perioperative red blood cell transfusion rates were lower in minimally invasive procedures (3.0% colectomy, 4.5% proctectomy) compared to open procedures (8.7% colectomy, 21.5% proctectomy). Open proctectomy was the strongest predictor of transfusion (OR 12.05; 95% CI, 8.94–16.26; p < 0.0001) followed by open colectomy (OR 2.59; 95% CI, 2.04–3.30; p < 0.0001). Preoperative factors including ASA class IV (OR 5.21; 95% CI, 1.09–24.82; p < 0.0382) and anemia (OR 4.14; 95% CI, 3.09–5.55; p < 0.0001) were also significantly associated with red blood cell transfusion. LIMITATIONS: The retrospective nature of the study may introduce selection bias. In addition, institutional practice patterns may limit the generalizability of findings. CONCLUSIONS: Patients undergoing elective minimally invasive colorectal surgery have very low rates of perioperative blood transfusions; thus, routine preoperative type and screen testing is likely unnecessary for this patient cohort. However, patients undergoing planned open operations, likely due to procedural complexity, and those who are ASA class IV, have preoperative anemia, or have anal cancer have higher transfusion risks and may benefit from selective testing. Implementing a risk-stratified approach based on surgical technique and patient comorbidities could potentially reduce unnecessary testing and associated health care costs. See Video Abstract. RE-TIPIFICACIÓN Y EVALUACIÓN PREOPERATORIAS: CÓMO IDENTIFICAR CUÁNDO ES NECESARIA UNA CIRUGÍA COLORRECTAL ELECTIVA ANTECEDENTES: El aumento en los costos de la atención médica exigen la reevaluación de las practicas preoperatorias de rutina. A pesar de las bajas tasas de transfusión en la cirugía colorrectal electiva, muchos hospitales continúan realizando pruebas de tipo y de cribado preoperatorios de forma rutinaria. El poresente estudio evalúa las tasas de transfusiones sanguíneas perioperatorias e identifica los factores asociados con éstas transfusiones para determinar la necesidad de pruebas de tipo y de cribado preoperatorios de forma rutinaria en cirugías colorrectales abdominales electivas. OBJETIVO: Evaluar las tasas de transfusión sanguínea perioperatoria y determinar los factores preoperatorios y quirúrgicos asociados con las transfusiones, con el fin de determinar si las pruebas de tipo y de cribado preoperatorias de forma rutinaria son necesarias en cirugías colorrectales abdominales electivas, en particular en el contexto de la cirugía mínimamente invasiva. DISEÑO: Estudio de cohortes retrospectivo. ESCENARIO: Clínica Mayo, 2019-2023. PACIENTES: Pacientes adultos sometidos a cirugías colorrectales abdominales electivas. Los criterios de exclusión incluyeron operaciones de emergencia y procedimientos no abdominales. INTERVENCIONES: Ninguna. PRINCIPALES MEDIDAS DE RESULTADOS: El resultado primario fue la incidencia de transfusión de hemoderivados intraoperatoriamente y postoperatoria inmediata (≤72 horas). Los resultados secundarios evaluaron la asociación entre las tasas de transfusión, el abordaje quirúrgico y las variables preoperatorias. RESULTADOS: De 4652 pacientes, 2770 se sometieron a cirugía mínimamente invasiva y 1882 a laparotomía. Las tasas de transfusión eritrocitaria perioperatoria fueron menores en los procedimientos mínimamente invasivos (3,0 % colectomía, 4,5 % proctectomía) que en los procedimientos abiertos (8,7 % colectomía, 21,5 % proctectomía). La proctectomía abierta fue el predictor más sólido de transfusión (OR: 12,05; IC del 95 %: 8,94-16,26; p < 0,0001), seguida de la colectomía abierta (OR: 2,59; IC del 95 %: 2,04-3,30; p < 0,0001). Los factores preoperatorios, incluyendo la clase ASA IV (OR 5,21; IC del 95 %: 1,09-24,82; p < 0,0382) y la anemia (OR 4,14; IC del 95 %: 3,09-5,55; p < 0,0001), también se asociaron significativamente con la transfusión de glóbulos rojos. LIMITACIONES: La naturaleza retrospectiva del estudio puede introducir sesgo de selección. Además, los patrones de práctica institucional pueden limitar la generalización de los hallazgos. CONCLUSIONES: Los pacientes sometidos a cirugía colorrectal mínimamente invasiva electiva tienen tasas muy bajas de transfusiones sanguíneas perioperatorias, por lo que las pruebas de detección y tipo de sangre preoperatorias de rutina probablemente sean innecesarias para esta cohorte de pacientes. Sin embargo, los pacientes sometidos a cirugías abiertas planificadas, probablemente debido a la complejidad del procedimiento, y aquellos con clase ASA IV, anemia preoperatoria o cáncer anal, tienen mayor riesgo de transfusión y podrían beneficiarse de pruebas selectivas. La implementación de un enfoque estratificado por riesgo basado en la técnica quirúrgica y las comorbilidades del paciente puede reducir las pruebas innecesarias y los costos de atención médica asociados. (Traducción—Dr. Xavier Delgadillo)

Abstract Objective The successful diagnosis and classification of lymphoid neoplasms in blood and bone marrow is the responsibility of the practicing pathologist. This guide provides a general “roadmap” for this process, from initial case recognition to final classification. Methods The integration of hematologic, morphologic, immunophenotypic, and genetic features for the full spectrum of precursor and mature B-cell, T-cell, and natural killer–cell neoplasms that typically manifest in blood and bone marrow is included. Results Classification systems for lymphoid neoplasms provide criteria for pathologists to render a diagnosis that is optimal for patient care, treatment, and outcome prediction. Conclusions This guide provides diagnostic strategies for lymphoid neoplasms encountered in blood and bone marrow specimens using both the International Consensus Classification and the World Health Organization fifth edition classification systems. Key tips are provided for each entity along with testing requirements, differential diagnosis, nonneoplastic mimics, and other unique features based on the experience of the Bone Marrow Pathology Group members.

Abstract Objective Despite exponential growth in artificial intelligence (AI) research for laboratory medicine and pathology, a significant gap exists between model development and clinical AI implementation. This article introduces a structured framework, the Clinical AI Readiness Evaluator (CARE), to bridge this gap and support the responsible adoption of AI in clinical laboratory settings. Methods Building upon the Machine Learning Technology Readiness Levels framework, we developed CARE specifically for the clinical laboratory environment by incorporating health care–specific requirements, regulatory considerations, and workflow integration needs. This framework was iteratively refined through practical application across diverse AI use cases within laboratory medicine and pathology. Results The CARE framework provides a systematic approach to AI development and implementation through 8 component workstreams: clinical use case, data, data pipeline, code, clinical user experience, clinical technology infrastructure, clinical orchestration, and regulatory compliance. Unlike generic AI frameworks, CARE distinguishes itself by emphasizing both health care and laboratory workflow integration, regulatory requirements, ethical considerations, and comprehensive validation for clinical contexts. The framework accommodates both internally developed models and commercial AI solutions, providing clear guidance through technology readiness levels and structured review processes. Conclusions The CARE framework addresses the unique challenges of implementing AI in laboratory medicine and pathology by providing a comprehensive roadmap from initial concepts through clinical deployment and maintenance. This article, the first in a series of 4, establishes the foundational AI lifecycle framework, while subsequent articles will explore data documentation, ethical AI considerations, and governance structures. By adopting this structured approach, laboratories can responsibly harness AI’s potential to enhance diagnostic accuracy and operational efficiencies and, ultimately, improve patient care.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare diffuse parenchymal lung disease representing 3% of all interstitial lung diseases. PLCH occurs either as part of multi-system Langerhans cell histiocytosis (LCH) or an isolated disease of the lung. Isolated involvement of lungs is observed in approximately 50–70% of LCH cases and the age of onset peaks between 20 and 40 years without gender difference. Cigarette smoking is the only identified environmental risk factor. PLCH is characterized by Langerhans cell infiltrates that in general are in a bronchiolocentric distribution. Pulmonary lesions can occur after chronic systemic disease or are an initial sign of disease. The aims of this study are to (1) report five rare cases of PLCH in adults; (2) discuss the relationship of PLCH with interstitial lung fibrosis; (3) provide a concise review of PLCH epidemiology, pathophysiology, diagnosis, treatment, and prognosis to improve the knowledge of PLCH by pneumologists and internal medicine physicians.

Abstract Background and Objectives Lucid episodes (LEs) in people living with late-stage dementia have been reported anecdotally. However, how this seemingly unexpected phenomenon is experienced by family caregivers is less known. Focusing on the two most common groups of informal caregivers, spouses and adult children, this study examined variability in family caregivers’ experiences with LEs—whether they exhibit differential appraisals of and responses to LEs. Research Design and Methods Using a sample of former/bereaved and current family caregivers from UsAgainstAlzheimer’s A-LIST, we conducted an online survey of spouse and child caregivers (N = 387). We conducted semistructured interviews among a subset of caregivers who witnessed a LE (n = 22). Results Overall, child caregivers were more likely to witness a LE than spouse caregivers. Among former/bereaved caregivers who witnessed a LE (n = 139), spouses were likely to report nonverbal communication during LEs, appraise LEs more negatively, and make changes in care decisions, such as end-of-life planning and financial decisions, compared to adult children. Among current caregivers who witnessed a LE (n = 80), spouses often reported no special circumstances preceding LEs, whereas children linked LEs to friend/family visits. No significant differences were found in positive and negative appraisals of LEs between current spouse and child caregivers. Content analysis of qualitative interviews revealed the contexts underlying these differences. Discussion and Implications Differences between spouses and adult children in their experiences with LEs are related to their different caregiving contexts, including relationship history, living arrangements, expectations, motivations, and caregiving resources.

Inherited platelet disorders (IPDs) are a group of rare conditions affecting platelet number, function, or both. Clinical manifestations vary widely, from asymptomatic cases to patients with severe bleeding, syndromic features, or early-onset blood cancers. Some are diagnosed due to family history. Early and accurate diagnosis—through both clinical and molecular evaluation—is essential for effective patient management and to avoid inappropriate treatments due to misdiagnosis. Genetic confirmation aids in prognosis, follow-up planning, family screening, genetic counseling, and donor selection for stem cell transplantation if required. However, diagnosing IPD is still challenging due to the disorders’ complexity and the limitations of current lab tests. This review outlines the diagnostic process for IPD and provides evidence-based, practical recommendations informed by scientific literature and clinical experience.