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Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

BACKGROUND: People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS: We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS: Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, −4.1 [95% CI, −6.9 to −1.4] mm Hg; 1-sided P =0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS: People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05869773.

PURPOSE Human epidermal growth factor receptor 2 (HER2), a transmembrane receptor with kinase activity involved in cell signaling through the RAS pathway, is expressed in osteosarcoma (OST). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate with a HER2-targeting monoclonal antibody, trastuzumab, linked to a topoisomerase I inhibitor. We report results of a phase II study of T-DXd in adolescents and young adults with HER2-positive relapsed, unresectable OST (ClinicalTrials.gov identifier: NCT04616560 ). METHODS Patients age 12-39 years with relapsed, unresectable OST were eligible for centrally evaluated HER2 expression screening by immunohistochemistry. Patients with >10% of OST cells with cytoplasmic or membranous HER2 expression of any intensity were eligible to receive T-DXd at 5.4 mg/kg intravenously once every 3 weeks for up to 2 years. The study used a 9 + 15 Simon's optimal two-stage design with a primary end point of event-free survival at 24 weeks. RESULTS Fifty patients were screened for HER2, and 41 met the inclusion criteria of 10% of OST cells having membranous or cytoplasmic HER2 expression. Nine eligible patients, two younger than 18 years, were enrolled and received T-DXd. With a single patient having more than 24 weeks of stable disease (SD) of the nine planned in the first stage, this study did not meet criteria to progress to stage II. The estimated SD rate at 24 weeks is 11.1%. The median (range) number of cycles of therapy was 2 (2-12). Grade 3 and 4 possibly related adverse events occurred in three of nine patients and included nausea, vomiting, tumor hemorrhage, cytopenias (n = 3), wound infection, and hypertension. CONCLUSION T-DXd did not demonstrate sufficient activity to expand enrollment to the planned second stage in patients with OST. No new safety signals were observed.

Abstract Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical–pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease‐modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences. Highlights We celebrate 40 years of NIA‐funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD. Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies. Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease‐modifying therapies. Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics. Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.

ABSTRACT Background Patients with cancer undergoing cardiac implantable electronic device (CIED) implantation face unique challenges. This study evaluates the outcomes and implications of CIED implantation in this population. Methods Using data from the National Readmission Database (NRD) from 2016 to 2019, we analyzed CIED implantations in patients aged ≥18 years, categorized by cancer status: no cancer, historical cancer, and active cancer. Multivariable logistic and linear regression models assessed associations with in‐hospital, 30‐day, and 90‐day outcomes, adjusting for various patient characteristics. Results A total of 748,957 CIED procedures were analyzed among which 13.3% were in patients with historical cancer and 3.8% with active cancer. Active cancer was linked to higher odds of pacemaker implantation but lower odds for ICD and CRT devices. Patients with active cancer experienced higher index hospitalization mortality (aOR 1.68; 1.50–1.89; p < 0.001), major adverse cardiovascular events (aOR 1.07; 1.02–1.14; p = 0.01), bleeding (aOR 1.36; 1.27–1.46; p < 0.01), and sepsis‐related (aOR 1.31; 1.19–1.44; p < 0.01) complications, with increased readmission rates at 30 (aOR 1.37; 1.30–1.44; p < 0.01) and 90 days (aOR 1.37; 1.31–1.44; p < 0.01) compared to those without cancer. Historical cancer was associated with better outcomes. Key predictors of adverse outcomes included chronic heart failure, kidney disease, cerebrovascular disease, and protein‐calorie malnutrition. Conclusions Patients with active cancer undergoing CIED implantation have an increased risk of in‐hospital complications and readmissions as compared to those without cancer.

The treatment landscape of B-cell lymphomas has significantly evolved in recent years with approval of novel targeted therapies. CD3 × CD20 bispecific antibodies and CD19-directed monoclonal antibodies and antibody–drug conjugates have demonstrated efficacy in relapsed/refractory follicular lymphoma (FL). Bruton tyrosine kinase (BTK) inhibitor–based regimens are emerging as effective treatment options for patients with TP53-mutated classical mantle cell lymphoma (MCL). Results from ongoing clinical trials suggest that the addition of CD3 × CD20 bispecific antibodies to chemoimmunotherapy improves outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, MCL, and DLBCL.

ABSTRACT Background Magnetic resonance elastography (MRE) has demonstrated potential in characterizing intracranial tumors, including glioblastoma. The influence of pathology on measurement consistency and interobserver agreement needs evaluation to promote MRE implementation as a quantitative biomarker. Purpose To assess repeatability and interobserver agreement of absolute and normalized magnitude of the complex shear modulus (| G *|), storage modulus ( G ′), and loss modulus ( G ″) in glioblastoma. Study Type Prospective. Population Thirteen adults (5 male, 8 female, mean age 66.23 years) with histopathologically confirmed glioblastoma. Field Strength/Sequence 3 T MRI, modified single‐shot spin‐echo echo‐planar imaging. Assessment Two same‐session MRE acquisitions were performed with patient repositioning. The solid tumor component was independently segmented by 2 observers on contrast‐enhanced T1‐weighted images co‐registered to MRE maps. Statistical Tests Repeatability was assessed using the repeatability coefficient, coefficient of variation, and Bland–Altman plots, and interobserver agreement by the intraclass correlation coefficient. The Wilcoxon signed‐rank test compared parameters and coefficients of variation between tumor‐normal‐appearing white matter and absolute and normalized measurements. Significance was set at 0.05. Results Tumor | G *| and G ′ showed repeatability coefficients of 0.07–0.08 kPa and 0.05 kPa, compared with 0.13 kPa (| G *|) and 0.15–0.16 kPa ( G ′) for normalized measurements. Coefficients of variation in tumor regions were 1.42% ± 1.12%–1.60% ± 1.41% for | G *| and 1.19% ± 0.96%–2.08% ± 2.22% for G ′, significantly lower than normalized values (4.82% ± 4.49%–4.21% ± 4.27% for | G *|; 5.12% ± 5.04%–5.45% ± 4.53% for G ′). Tumor | G *| and G ′ showed excellent interobserver agreement (intraclass correlation coefficients 0.97 and 0.95). Tumor G ″ demonstrated higher variability than | G *| and G ′ (coefficients of variation 8.58% ± 7.69%–7.51% ± 6.73%), with no significant difference between absolute and normalized measurements ( p = 0.14). Data Conclusion Tumor | G *| and G ′ are the most repeatable metrics in glioblastoma. Normalization reduces measurement repeatability due to normal‐appearing white matter variability. The small sample size ( n = 13) limits generalizability. Evidence Level 2. Technical Efficacy Stage 2.

This study examines the relevance of minimum case volume recommendations in contemporary practice.