Citations

Abstract Background Historically, 25-hydroxyvitamin D (25OHD) assays have under- or over-recovered 25-hydroxyvitamin D2 (25OHD2), but assay manufacturers have modified their reagents to address this problem. In this study, we compared the second- and third-generation Roche assays as well as two contemporary offerings from Diasorin and Beckman against liquid chromatography–tandem mass spectrometry (LC-MS/MS). Methods We identified 50 remnant serum samples with 25OHD concentrations from across the analytical range of the second-generation Roche assay. To increase 25OHD2 representation, we identified 25 additional samples from individuals prescribed high-dose vitamin D2 supplements. We tested samples on Roche assays and circulated to laboratories performing Beckman and Diasorin 25OHD assays. We tested samples by LC-MS/MS to obtain concentrations for 25OHD2 and 25-hydroxyvitamin D3. Results Mean overall bias for each assay was 5.1 ng/mL or less against the LC-MS/MS measurement; mean proportional bias was 8.7% to 12.1%. Some individual specimens had much larger bias. 25OHD2 was under-recovered on average, but the bias for the third-generation Roche assay represents a significant improvement over the previous assay, and mean bias for current generation assays was no worse than −3.2 ng/mL. In most cases, clinical classification by automated assay values agreed with clinical classification by LC-MS/MS; where present, disagreements occurred near classification thresholds. Conclusions Automated 25OHD assays continue to improve, and 25OHD2 recovery no longer appears to be a significant concern for the assays evaluated here. All assays evaluated were adequate for clinical classification of vitamin D nutritional status and are suitable for routine use, including in patients prescribed high-dose vitamin D2.

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from Schwann cells and characterized by marked cellular and molecular heterogeneity. Although bulk multi-omic studies have provided valuable insights into MPNST biology, recent advances in single-cell profiling have deepened our understanding of the tumor microenvironment and molecular mechanisms underlying malignant transformation. Single cell analyses have revealed distinct Schwann cell-like, malignant neural crest-like, immune, and stromal cellular subpopulations within MPNSTs and their precursor lesions. Comparative profiling of MPNSTs, neurofibromas, and atypical neurofibromatous neoplasms of uncertain biologic potential, suggest that MPNST progression involves Schwann cell dedifferentiation into a more primitive, stem-like state. In this review, we summarize key discoveries from single-cell characterization studies, and discuss how these findings illuminate MPNST tumorigenesis, cellular plasticity, and potential therapeutic vulnerabilities.

Background: Discovering risk biomarkers in small benign breast disease (BBD) biopsies is constrained by scarce tissue and microanatomic heterogeneity of terminal duct lobular units (TDLUs). We tested whether tissue-sparing tissue microarray (TMA)–based Digital Spatial Profiling (DSP) can deliver reproducible, biologically coherent protein measurements across benign lobules and breast cancers (BCs), and how well DSP aligns with standard immunoassays. Methods: We performed a pilot using tissues from the Mayo Clinic BBD cohort using TMAs representing four contexts: terminal duct lobular units (TDLUs) from BBD biopsies preceding BC and matched BBD-controls, subsequent BCs, and BC-associated TDLUs. We profiled 79 proteins by DSP (37 retained after QC) and benchmarked against chromogenic IHC and OPAL immunofluorescence. Reproducibility was evaluated using intraclass correlation coefficients (ICCs), cross-platform agreement (weighted kappa), marker correlations, and mixed-effects models with false-discovery-rate (FDR) control. Results: We analyzed 368 BBD-TDLU cores (88 cases; 88 controls), 204 BC cores and 110 BC-associated TDLU cores. ICCs were highest in BC tissues, and lower in BC-associated TDLUs and BBD-TDLUs. Agreement was slight–to-fair in TDLUs but moderate (ER/PR) to substantial (BCL2) in BC. DSP recapitulated expected immunologic correlations (CD45 with T-cell, B-cell, and macrophage markers) and tissue-type gradients (BC > BC-associated TDLUs > BBD-TDLUs). Exploratory case–control differences in BBD-TDLUs did not persist after FDR control. Conclusions: TMA-based DSP is feasible in archival breast tissues and yields biologically coherent, cross-platform-benchmarked profiles that are particularly robust in BC, while conserving scarce TDLUS and clarifying current limits of single-marker risk stratification from benign lobules. These data provide a foundation for refined sampling and expanded panels in future TDLU-focused studies.

ABSTRACT Pharmacists play a critical role in optimizing medication use, especially in vulnerable populations such as those with chronic kidney disease (CKD). Despite strong evidence and recent guideline endorsements, many pharmacists continue to rely on the Cockcroft–Gault (C‐G) equation for medication dosing. This opinion paper issues a call to action for the widespread adoption of a race‐free, body surface area–adjusted estimated glomerular filtration rate (eGFR BSAadj ) for medication‐related decision‐making, as endorsed by the 2024 Kidney Disease: Improving Global Outcomes CKD guidelines and the National Kidney Foundation and the American Society of Nephrology Taskforce. Persistent variability in pharmacy practice, institutional protocols, and pharmacy education underscores the need for coordinated change. We urge health systems to integrate eGFR BSAadj into electronic health records and clinical decision support to enhance medication decision‐making; institutions to align protocols with contemporary eGFR‐based prescribing standards; pharmacy educators to contemporize and standardize education on kidney function assessment and medication dosing; and regulatory bodies to update licensure and board examinations. The pharmacy profession must act decisively in order to align with evidence‐based, equitable kidney‐related dosing practices and ensure optimal medication management for all patients.

ABSTRACT Scapular winging (SW) describes abnormal scapular mechanics from weak stabilizing muscles or altered neural innervation. While electromyography (EMG) helps differentiate between myo‐ or neuropathic SW etiologies and determine the extent of muscle involvement, pediatric EMG may be limited due to the high risk of surrounding structures, small body habitus, and pain tolerance. Herein is a case of pediatric SW following anterior neck lymphadenopathy resection in which EMG was limited. Neuromuscular ultrasound (NMUS) showed asymmetric trapezius thinning and hyperechogenicity, revealing more expansive involvement than was previously known. NMUS is a painless, validated tool to augment the diagnostic capability of EMG and clarify the extent of neuromuscular involvement in SW from both a prognostic and rehabilitation point of view.