Citations

Abstract OBJECTIVE AND SCOPE A panel of clinicians, subject‐matter experts, and guideline methodologists convened by the Alzheimer's Association conducted a systematic review and formulated evidence‐based recommendations for using blood‐based biomarkers (BBMs) in the diagnostic workup of suspected Alzheimer's disease (AD) within specialized care settings. The scope focuses on individuals with objective cognitive impairment, including those with mild cognitive impairment (MCI) or dementia, who are undergoing evaluation by providers trained and experienced in memory disorders, where AD is the suspected underlying etiology. METHODS The panel conducted a systematic review to assess the diagnostic accuracy of BBMs in detecting AD pathology. The BBMs of interest included plasma phosphorylated‐tau (p‐tau) and amyloid‐beta (Aβ) tests measuring the following analytes: p‐tau217, ratio of p‐tau217 to non‐p‐tau217 ×100 (%p‐tau17), p‐tau181, p‐tau231, and ratio of Aβ42 to Aβ40. The reference standard tests included cerebrospinal fluid (CSF) AD biomarkers, amyloid positron emission tomography (PET), or neuropathology. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence and the GRADE evidence‐to‐decision (EtD) Framework to develop its recommendations. RECOMMENDATIONS The key recommendations in this Clinical Practice Guideline (CPG) are: (1) BBM tests with ≥90% sensitivity and ≥75% specificity can be used as a triaging test and (2) BBM tests with ≥90% sensitivity and specificity can serve as a substitute for amyloid PET imaging or CSF AD biomarker testing in patients with cognitive impairment presenting to specialized care for memory disorders. The panel cautions users of this guideline that there is significant variability in diagnostic test accuracy and many commercially available BBM tests do not meet these thresholds, especially using a single cutoff. Additionally, these tests do not serve as a substitute for comprehensive clinical evaluation by a healthcare professional and should be used only as part of a full diagnostic workup of patients with cognitive impairment presenting to specialized care settings, and with careful consideration of pretest probability of AD pathology. CONCLUSIONS AND PRACTICAL IMPLICATIONS This CPG provides performance‐based, brand‐agnostic recommendations for the use of BBMs in the diagnostic workup of suspected AD within specialized care settings. By linking recommendations to a systematic review and associated living updates, and using a robust and transparent methodology, the guideline ensures scientific rigor, adaptability, and sustained relevance as evidence evolves. Clinicians are encouraged to stay informed about emerging paradigms—such as biomarker combinations or ratios and multi‐threshold testing—that may further refine the diagnostic accuracy of BBMs as the field evolves.

Background: Cholestatic liver diseases, including primary sclerosing cholangitis, are characterized by biliary fibroinflammation. TGFβ-activated cholangiocytes release signals that recruit immune cells and activate myofibroblasts, promoting inflammation and extracellular matrix (ECM) deposition. TGFβ also regulates stearoyl-CoA desaturase (SCD), an enzyme involved in lipid signaling. Yet, the role of SCD or its inhibitor, Aramchol, in biliary fibroinflammation had not been studied. Methods and Results: Mdr2 -/- with established biliary fibrosis and 3,5-diethoxycarboncyl-1,4-dihydrocollidine (DDC) diet-fed mice were treated with Aramchol meglumine (12.5 mg/kg/day). Hepatic fibrosis was assessed by qPCR, Picrosirius red staining, immunofluorescence, and hydroxyproline content. Human H69 or murine large cholangiocyte cell lines stimulated with TGFβ, as well as PSC-derived cholangiocytes (PSC-C), were treated with Aramchol or SCD siRNA. RNA-seq, fibroinflammatory marker expression, peroxisome proliferator-activated receptor (PPAR) activity, and targeted fatty acid profiling were performed. Aramchol treatment significantly reduced hepatic ECM gene expression, inflammatory cytokines ( Il6 , Tnfa ), collagen content, and myofibroblast activation (aSMA staining) in both mouse models. In TGFβ-stimulated H69 cells, Aramchol suppressed hepatic fibrosis pathways and enhanced PPAR signaling. Aramchol also reduced the expression of fibrotic markers, myofibroblast-activating mediators ( VEGFA and PDGFB ), and IL6, mirroring the effects of SCD knockdown. In PSC-C, Aramchol significantly downregulated SCD, VEGFA and IL6 . Conversely, PPARα and -γ activity and fatty acid agonist, linoleic acid levels were increased in cholangiocyte cell lines. Conclusions: Aramchol attenuates and prevents biliary fibrosis in mouse models of cholestatic liver disease by inhibiting TGFβ-induced fibroinflammatory mediators and activating PPARa/γ in cholangiocytes. These findings, combined with its favorable clinical safety profile, support the potential of Aramchol as a therapeutic candidate for PSC.

BACKGROUND/OBJECTIVE Patient- and family-centered rounds (PFCR) have become a pediatric standard of care. However, rounds experiences of families using languages other than English (LOE)—particularly languages other than English or Spanish (LOES; eg, Arabic)—receive less focus. We aimed to identify differences in PFCR communication and engagement by language. METHODS We analyzed postintervention data from a 21-center structured PFCR study, assessing communication practices, quality, and family and nurse engagement during PFCR. Logistic regression adjusted by site compared PFCR between families using (1) LOE vs English, (2) Spanish vs English, and (3) LOES vs English. RESULTS Among 3051 PFCR encounters, 348 (11.4%) involved LOE (Spanish = 260; LOES = 85). Interpretation was not used in 7.2%, 5.8%, and 9.4% of encounters using LOE, Spanish, and LOES, respectively. PFCR in the following groups had lower adjusted odds (adjusted odds ratio [95% CI]) for the following domains: (1) LOE vs English: including providing verbal patient summaries (0.66 [0.46–0.95]), explaining diagnoses and differentials (0.62 [0.44–0.88]), family engagement (0.34 [0.20–0.57]), nursing inclusion (0.75 [0.60–0.93]), and nursing engagement (0.69 [0.52–0.90]). (2) Spanish vs English: diagnoses/differentials being explained (0.56 [0.37–0.85]), family engagement (0.35 [0.18–0.67]), nursing inclusion (0.77 [0.59–1.00]), and nursing engagement (0.68 [0.52–0.89]). (3) LOES vs English: families sharing concerns (0.66 [0.47–0.93]), family engagement (0.30 [0.16–0.54]), and nursing inclusion (0.74 [0.55–0.99]). CONCLUSION Even after implementing a PFCR intervention, families using LOE—especially LOES—experienced significant disparities in communication and engagement. Future approaches to improving PFCR should emphasize language access and promote nurse and family engagement for families using LOE, particularly LOES.

Abstract The initial method of detection (MOD) refers to the first imaging examination, physical symptom, or clinical sign that prompts further investigation and ultimately leads to a new breast cancer diagnosis. The MOD is assigned at the patient level and falls into 1 of 3 categories: screening in asymptomatic patients, detection by patients or health care providers, or neither of the above. The MOD should be assigned prospectively by the radiologist when interpreting an examination with a final BI-RADS category of 4 or 5, before image-guided biopsy and breast cancer diagnosis. The MOD is not assigned to examinations classified as BI-RADS category 0, 1, 2, 3, or 6, nor is it assigned in the setting of an active breast cancer diagnosis. This Clinical Practice article addresses frequently asked questions and challenging clinical scenarios compiled by the American College of Radiology’s Screening and Emerging Technology Committee to guide consistent MOD assignment. For example, if a patient presents with a lump but is ultimately found to have a suspicious finding requiring biopsy in the contralateral breast, the MOD should reflect the reason for presentation, the patient-detected symptom (Pat), even if the cancer itself is asymptomatic. By increasing awareness of MOD and standardizing MOD reporting practices, radiologists can contribute to improved data collection. While MOD is not currently tracked in U.S. cancer registries, its systematic collection may offer valuable insights into screening effectiveness, technology performance, and disparities in cancer detection. Standardized MOD reporting has the potential to strengthen early detection efforts and improve outcomes across diverse clinical settings.

Importance Women diagnosed with breast cancer at a young age are felt to have a higher risk for locoregional recurrence (LRR) regardless of type of local therapy. Objective To assess the long-term incidence of isolated LRR by molecular subtype in a modern multicenter cohort of young women. Design, Setting, and Participants This cohort study, a multicenter prospective study named the Young Women’s Breast Cancer Study, enrolled 1302 women diagnosed with breast cancer at 40 years or younger from 2006 to 2016. Treatment information and incident LRR (ipsilateral breast/chest or lymph node recurrence) were self-reported on study surveys and confirmed with medical record review; molecular subtype was determined by record review. Analysis was reported from February 2023 to May 2025. Main Outcomes and Measures Cumulative incidence of isolated LRR was calculated using the Kaplan-Meier method; hazard ratios were estimated by Cox proportional hazards regression. Results The cohort included 1135 women with stage I through III breast cancer who had a median follow-up of 10.1 years (range, 0.4-16.3 years). The age at diagnosis was younger than 30 years for 145 patients (12.8%), 31 to 35 years for 318 patients (28.0%), and 36 to 40 years for 672 patients (59.2%). There were 59 isolated local recurrences (5.2%) and 4 isolated regional recurrences (0.4%). Among patients with local therapy and subtype data available (n = 1128), 366 (32%) had luminal A–like tumors; 240 (21%), luminal B–like tumors; 231 (20%) luminal ERBB2 positive (+)–like (formerly HER2 positive); 90 (8%) ERBB2 +-like; and 201 (18%) triple negative. A total of 346 women (30%) had breast-conserving therapy (BCT) (98% of whom had radiation), 296 (26%) unilateral mastectomy, and 487 (43%) bilateral mastectomy. Of women who had mastectomy, 425 (54%) had radiation. The cumulative incidence of LRR at 10.1 years by subtype was as follows: luminal A, 4.4% (range, 1.0%-6.9%); luminal B, 4.7% (range 1.8%-7.7%); luminal ERBB2 +, 6.1% (range, 3.1%-8.3%); ERBB2 +, 2.2% (range, 0%-6.3%); and triple negative, 6.5% (range, 4.2%-10.1%). The cumulative incidence of LRR by locoregional treatment type at 10.1 years was 6.7% after BCT (range, 4.3%-10.1%), 6.5% after mastectomy without radiation (range, 0%-7.7%), and 2.4% after mastectomy with radiation (range, 1%-4.2%). Although mastectomy with radiation was associated with the lowest risk of LRR on multivariable analysis, when examined within molecular subtype, there were no differences seen. Conclusions and Relevance In this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumor subtype. Concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.

Objectives: To assess the long-term effects of 4 years of menopausal hormone therapy (mHT) on the brain’s white matter architecture in women who initiated mHT within 3 years of menopause onset. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, double-blind, randomized, placebo-controlled 4-year mHT trial with treatment arms of oral conjugated equine estrogens (oCEE), transdermal 17β-estradiol (tE2), and placebo in recently postmenopausal women. KEEPS Continuation was an observational follow-up of KEEPS participants. White matter integrity was evaluated in KEEPS Continuation participants 10 years after KEEPS completion using white matter hyperintensity volume, diffusion magnetic resonance imaging (dMRI) techniques, and cerebral infarcts. Linear regression models were fitted for each brain region to evaluate if there were differences in white matter between KEEPS treatment arms. Results: There was no evidence to suggest the long-term effects of 4 years of mHT on brain white matter in KEEPS Continuation participants [n=266, mean age 67 (58-73)]. No differences in dMRI metrics were found in each of the treatment arms (oCEE n=70; tE2 n=79) when compared to placebo (n=94), following a false discovery rate adjustment for multiple comparisons. There were no statistically significant differences in white matter hyperintensity volume or infarct occurrence when comparing each of the treatment arms to placebo. Conclusions: We found no evidence of the long-term effect of 4-year mHT on white matter integrity when compared to placebo, consistent with emerging evidence of the safety of short-term use of mHT in recently postmenopausal women.

Abstract Glioblastoma is the most common type of malignant primary brain tumor and a major cause of morbidity and mortality. In 2021, the World Health Organization updated the classification of Central Nervous System (CNS) tumors to restrict glioblastomas to isocitrate dehydrogenase-wildtype (IDHwt) tumors, improving understanding of the prognosis and optimal therapy for these tumors. This revision also enables more homogeneous populations of patients to be enrolled in clinical trials, facilitating the evaluation of novel therapies. In this updated consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of patients with glioblastoma is discussed. In addition, novel therapies such as immunotherapies, viral therapies, targeted molecular therapies, theranostics, and antibody–drug conjugates will be reviewed, as well as the current challenges and future directions for research.