Citations

Effective healthcare referral triage poses a significant challenge, especially extracting referral notes on time for scheduling. To offset this issue, this study aims to develop an optimized Random Forest classifier to recreate the referral notes content and identify patients requiring Spinal Cord Stimulation procedures. A performance index was introduced to improve accuracy, while a consistency index was designed to prevent overfitting. The optimized classifier, with the optimal selection at the number of estimates being 5 trees and tree depth being 4, achieved an accuracy of 0.74 with a lower standard deviation, demonstrating its reliability and effectiveness.

ABSTRACT Osteoporosis is a chronic disease mainly prevalent in older people. A hip fracture, its most devastating complication, is associated with a one in five chance of mortality in the first year. This review discusses emerging risk factors for bone fragility including diabetes, sarcopenia, and bariatric surgery. Recency of fracture represents an imminent risk that deserves prompt recognition. The new FRAXplus calculator accounts for additional risk factors to refine existing risk stratification. Advances in imaging techniques such as trabecular bone score and radiofrequency echographic multi-spectrometry may have potential roles in specific populations. Treatment of osteoporosis requires a multifaceted approach. Non-drug interventions include fall prevention and resistance exercises, supplementation with calcium, vitamin D and possibly vitamin K, and effective bridging of care gaps with fracture liaison services. An overview of drug therapy is provided, drawing attention to the importance of sequential therapy starting with potent anabolic agents for the patients at the highest risk, as opposed to a traditional step-up approach. An individualized, goal directed care plan is necessary for a treat-to-target approach, with total hip bone mineral density being the best specific target. Future research in cellular senescence points to the role of senolytics and senomorphics to alleviate osteoporosis, among other age related conditions.

Abstract INTRODUCTION African American (AA) individuals are underrepresented in biomarker studies for Alzheimer's disease (AD). Biomarkers that reflect the heterogeneity of AD and achieve the greatest accuracy across populations are sorely needed. METHODS Untargeted proteome measurements were obtained using the SomaScan 7k platform to identify novel plasma biomarkers for AD in AA participants with clinical diagnoses of AD dementia ( n = 181) and cognitively unimpaired (CU, n = 142). Machine learning was used to identify a set of plasma proteins that yielded the best classification accuracy. RESULTS A set of 36 proteins achieved an area under the curve (AUC) of 0.94 to classify AD dementia versus CU, a 16% improvement over age, sex, and apolipoprotein E ( APOE) . This finding was replicated in multiple plasma and brain datasets (AUCs 0.73–0.97). Our findings underscore the importance of matrisome and cerebrovascular dysfunction in AD pathophysiology. DISCUSSION This study demonstrates the potential of biomarker discovery through untargeted plasma proteomics and machine learning. Highlights Conducted large‐scale plasma proteomics in Alzheimer's disease (AD) versus cognitively unimpaired controls. Machine learning biomarker discovery was replicated in an independent cohort. Novel set of proteins distinguishes AD versus controls with high accuracy (area under the curve [AUC] = 0.94). Achieved reproducibility across multiple replication cohorts (AUC = 0.73–0.97). Network analyses implicates matrisome biology and cerebrovascular dysfunction.

ABSTRACT Introduction Although liver transplantation (LT) rates have increased globally, the demand for organs still exceeds the supply. This review highlights cultures with significant influences on organ donation and LT. Methods We performed a literature search for articles related to cultures, ethnologies, philosophies, policies, religions, socio‐economic factors, and other influences affecting organ donation in LT around the world. Results There are astonishing similarities between different cultures. In Africa, Asia, and Europe, people often view the postmortem bodies as sacred and believe that their bodies are gifts from “God” or ancestors. To respect the gift of life, to have a chance in reincarnation, or to enjoy life after death, many believe that their bodily sanctity must be preserved. In Asia, Europe, and Latin America, there is a general reluctance to speak about death. Religions also play an important role in people's views on organ donation. Different regions around the world have similar challenges to organ donation, such as misconceptions about organ trafficking, political and economic instability, and a lack of governmental or religious support. Conclusion Addressing the complexities of organ donation and LT requires a multifaceted approach. Culturally sensitive education tailored to diverse communities can dispel myths and misconceptions surrounding organ donation. Fostering partnerships between healthcare providers, religious leaders, community organizations, and policymakers can further facilitate open dialogues and promote organ donation as a noble act to save lives. Social Media Similar cultures around the world post challenges for organ donation. Organizations should foster partnerships between healthcare providers, politicians, and religious leaders to promote donation.

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment. Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials.

Abstract Background The radiation oncology clinical practice involves many steps relying on the dynamic interplay of abundant text data. Large language models have displayed remarkable capabilities in processing complex text information. But their direct applications in specific fields like radiation oncology remain underexplored. Purpose This study aims to investigate whether fine‐tuning LLMs with domain knowledge can improve the performance on Task (1) treatment regimen generation, Task (2) treatment modality selection (photon, proton, electron, or brachytherapy), and Task (3) ICD‐10 code prediction in radiation oncology. Methods Data for 15 724 patient cases were extracted. Cases where patients had a single diagnostic record, and a clearly identifiable primary treatment plan were selected for preprocessing and manual annotation to have 7903 cases of the patient diagnosis, treatment plan, treatment modality, and ICD‐10 code. Each case was used to construct a pair consisting of patient diagnostics details and an answer (treatment regimen, treatment modality, or ICD‐10 code, respectively) for the supervised fine‐tuning of these three tasks. Open source LLaMA2‐7B and Mistral‐7B models were utilized for the fine‐tuning with the Low‐Rank Approximations method. Accuracy and ROUGE‐1 score were reported for the fine‐tuned models and original models. Clinical evaluation was performed on Task (1) by radiation oncologists, while precision, recall, and F‐1 score were evaluated for Task (2) and (3). One‐sided Wilcoxon signed‐rank tests were used to statistically analyze the results. Results Fine‐tuned LLMs outperformed original LLMs across all tasks with p value ≤ 0.001. Clinical evaluation demonstrated that over 60% of the fine‐tuned LLMs‐generated treatment regimens were clinically acceptable. Precision, recall, and F1‐score showed improved performance of fine‐tuned LLMs. Conclusion Fine‐tuned LLMs demonstrated statistically significant improvements over original LLMs upon three clinically important tasks in radiation oncology. This study explored the feasibility of applying fine‐tuned LLMs in radiation oncology, inspiring further development of utilizing LLMs to assist with radiation oncology tasks.

Abstract Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of post-approval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell–associated neurotoxicity syndrome in 11% (2.2% grade ≥3), with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR or better in 45%. With 10.1 months of median follow-up, the estimated median progression-free survival (PFS) was 5.8 months and 12-month overall survival was 61%. Independent predictors of less than very good PR and shorter PFS included BCMA-directed chimeric antigen receptor T-cell therapy in the previous 9 months, high disease burden, lymphopenia, and elevated ferritin. Significance: T cell–engaging bispecific antibodies such as teclistamab represent an important new treatment modality for multiple myeloma and other blood cancers. This study evaluates the real-world safety and efficacy of teclistamab, including its activity in populations not represented in the initial phase I/II study, and identifies clinical variables associated with treatment response. See related commentary by Zweegman et al., p. 542

ImportanceUptake of human papillomavirus (HPV) vaccination varies by characteristics, exposing some children to higher HPV cancer risks than others.ObjectiveTo examine whether the effectiveness of a multilevel intervention on HPV vaccination differed by race and ethnicity, rurality, and Area Deprivation Index (ADI) in children ages 11 to 12 years.Design, Setting, and ParticipantsA stepped-wedge cluster randomized trial was conducted from April 2018 to August 2022 among children at 6 Mayo Clinic primary care practices in Minnesota to improve HPV vaccination. This secondary analysis was performed from March to June 2024.InterventionA multilevel intervention that included parent reminder/recall letters, which alerted parents of children due or past due for vaccination, and health care professional audit/feedback reports, which alerted health care professionals of their own vaccination rates.Main Outcome and MeasureVaccine initiation (first dose of the 2-dose HPV vaccine) and vaccine completion (second dose) were the primary study outcomes. In this secondary analysis, the effect of the intervention on HPV vaccine initiation and completion by race and ethnicity, rurality, and ADI quartiles (Qs) was assessed.ResultsA total of 6232 children aged 11 to 12 years (3285 [52.7%] male; 3481 [55.9%] aged 11 years and 2751 [44.1%] aged 12 years) were included in the analysis. Of the study participants, 304 (4.9%) were Asian, 561 (9.0%) Black, 146 (2.3%) Hispanic, 4501 (72.2%) White, and 720 (11.6%) other, including American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, Other Pacific Islander, Samoan, unable to provide, unknown, chose not to disclose, or other unspecified. A total of 5434 participants (87.2%) were urban residents, and 2794 (44.8%) resided in ADI Q2 areas. With usual care, HPV vaccine initiation and completion rates were significantly lower with each increasing ADI quartile (initiation: Cochran-Armitage test for trend [SE], −0.02 [0.01]; P < .001; completion: Cochran-Armitage test for trend [SE], −0.05 [0.01]; P < .001) but did not differ by children’s race and ethnicity or rurality. With the intervention, vaccine initiation increased significantly for most children (range of rates, 9.2% [95% CI, 5.2%-13.3%] to 24.0% [95% CI, 7.5%-40.6%]) except those with Black race, in rural settings, and in ADI Q4 (highest area deprivation); vaccine completion increased significantly for most children (range of rates, 19.4% [95% CI, 5.5%-33.3%] to 31.2% [95% CI, 12.1%-50.3%]) except for those in ADI Q4.Conclusions and RelevanceIn this secondary analysis of a cluster randomized trial, a multilevel intervention was associated with increased HPV vaccination for most children but had limited effect for those residing in areas of highest deprivation. Future research should explore other intervention strategies that would effectively promote HPV vaccination among families in socioeconomically disadvantaged areas to reduce HPV vaccination disparities.Trial RegistrationClinicalTrials.gov Identifier: NCT03501992

ImportanceEtiologic heterogeneity in breast carcinogenesis needs to be well characterized for targeted prevention. Associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and breast cancer intrinsic-like subtypes are not well understood.ObjectiveTo examine whether exogenous hormone use is differentially associated with breast cancer subtypes and to evaluate heterogeneity by intrinsic-like subtypes.Design, Setting, and ParticipantsThis study pooled data from 31 nested and population-based case-control studies involved in the Breast Cancer Association Consortium. The study population included individuals with breast cancer and control participants from 13 case-control studies nested in prospective cohorts (recruited between 1982 and 2011) and 18 population-based case-control studies (recruited between 1990 and 2013). Data analysis was performed in June 2024.ExposureMHT use (estrogen-progestin therapy [EPT] or estrogen-only therapy [ET]) in postmenopausal women and OC use in premenopausal women (never, past use, or current use).Main Outcomes and MeasuresBreast cancer intrinsic-like subtypes (luminal A–like, luminal B–like, luminal B–ERBB2 [formerly HER2 or HER2/neu]-like, ERBB2 enriched–like, or triple-negative) were determined by immunohistochemistry of tumor sections. Polytomous logistic regression was performed to estimate the association between exogenous hormones and risk of breast cancer by intrinsic-like subtypes. Analyses by subtypes were stratified by body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; healthy weight, 18.5-<25; overweight, 25-<30; or obesity, ≥30).ResultsThis study included 42 269 individuals with breast cancer (11 901 [28.2%] premenopausal and 30 368 [71.8%] postmenopausal; 23 353 [55.2%] had a known intrinsic-like subtype) and 71 072 control participants. The mean (SD) age of all participants was 57.9 (10.9) years. In postmenopausal women, associations between current MHT use (EPT or ET) and breast cancer differed by subtype. Current EPT users with healthy weight were more likely to be diagnosed with luminal A–like (odds ratio [OR], 2.51 [95% CI, 2.26-2.80]) or luminal B–ERBB2-like (OR, 1.95 [95% CI, 1.61-2.37]) subtypes. These associations were attenuated but remained for individuals with overweight (OR, 1.40 [95% CI, 1.02-1.92]) or obesity (OR, 1.68 [95% CI, 1.01-2.78]). EPT use increased the odds of being diagnosed with luminal B–like tumors solely in women with healthy weight (OR, 1.47 [95% CI, 1.17-1.86]). Current ET use was positively associated with luminal A–like disease in women with healthy weight only (OR, 1.16 [95% CI, 1.01-1.32]), showing inverse associations with higher BMI (obesity: OR, 0.65 [95% CI, 0.50-0.85]). In premenopausal women, recent OC use was associated with luminal B–ERBB2-like (OR, 1.50 [95% CI, 1.09-2.08]), ERBB2 enriched–like (OR, 2.33 [95% CI, 1.55-3.51]), and triple-negative (OR, 1.75 [95% CI, 1.33-2.29]; P < .04 for heterogeneity) tumors.Conclusions and RelevanceIn this study, clear differences were observed in associations between current EPT use and luminal-like breast cancer subtypes and other subtypes. EPT users with healthy weight were more likely to be diagnosed with luminal-like breast cancer compared with nonusers. Subtype heterogeneity was less apparent in associations of OC and ET use. Future studies on contemporary formulations, patterns of use, and routes of administration of exogenous hormone usage are warranted.