Citations

Abstract Peanut allergy is a leading cause of food-induced allergy (prevalence of ∼1%). The diagnosis relies on evaluating clinical symptoms consistent with peanut exposure, supported by the detection of total peanut specific IgE (sIgE) and peanut component IgE antibodies (Ara h1, Ara h2, Ara h3, Ara h6, Ara h8, Ara h9 and Bet v2) through serum or skin testing. However, sensitization patterns across different ages and regions in the United States remain largely unknown. In this study, we investigated regional and demographic patterns of peanut component sensitization in a large U.S. population tested for suspected peanut allergy. Retrospective data were collected from 13,702 individuals tested at Mayo Clinic Laboratories. sIgEs were measured using the ImmunoCAP system (Thermo Fisher Scientific). Samples with detectable total peanut sIgE (≥0.1 kU/L) were reflexed to testing for seven peanut component IgEs. Statistical analyses including linear regression and correlation matrix analysis were conducted using R Studio. Regional differences were assessed using care provider zip code information. Among the study population, 92.0% (12,604 of 13,702) had detectable total peanut sIgE, with the Western U.S. region exhibiting the highest detectable rate (95.6%), and the Southeast the lowest (85.6%) (p < 0.001). On average, 3.38 different component IgEs were detectable per person with a detectable total peanut sIgE; 7.1% (892) had no detectable component IgEs, possibly due to antibodies against other peanut components. Correlation analysis revealed strong associations between Ara h2 and Ara h6 (r = 0.94), with moderate correlations observed between Ara h2, Ara h3, and Ara h6 to Ara h1 (r ranging from 0.72 to 0.77). Age-stratified analysis indicated higher total peanut sIgE detectable rates in children and adolescents (95.2%, ≤18 years) compared to adults (76.5%, >18 years). Interestingly, adults were more likely than children to have negative results for all component IgEs. Sensitization rates to different peanut components varied, with Ara h2 (77.5%) and Ara h6 (73.2%) being the most frequently detected, followed by Ara h1 (56%), and Ara h3 (47.3%). Lower detectable rates were observed for Ara h8, Ara h9, and Bet v2 (34.8%, 26.1% and 22.7%, respectively). Regional analysis showed consistently high detectable rates for Ara h2 and Ara h6 (>70%) across most areas (p < 0.001) with slightly lower rates in the Southwest (<63%). Bet v2, despite its overall low prevalence (<24%), had a relatively higher detectable rate in the Southwest (29%). This study provides valuable insights into potential demographic and geographic factors influencing peanut allergy sensitization. Our study demonstrates that peanut sensitization patterns vary by age and geographic location. Children and adolescents exhibit higher detectable rates for total peanut sIgE and component IgEs compared to adults, with Ara h2 and Ara h6 as the most frequently detected and highly correlated components.

Abstract Introduction/Objective Microglandular adenosis (MGA) of the breast is an uncommon lesion characterized by a benign course. However atypical MGA (AMGA) and MGA-associated carcinoma have been described, suggesting that MGA may represent a non-obligate precursor of carcinoma. We report five cases of MGA-associated breast carcinoma and describe the key pathological features of this entity. Methods/Case Report Five cases of MGA-associated breast carcinoma were identified. Clinical data, histologic and immunohistochemical characteristics were reviewed and analyzed. Results All cases involved women with ages ranging 48 to 75 with a median of 70. Four of five cases demonstrated invasive carcinoma, while one case showed ductal carcinoma in-situ (DCIS). Invasive carcinomas encompassed various histologic types: metaplastic carcinoma with chondromyxoid matrix production (2 cases), invasive carcinoma with secretory features (1 case), and invasive carcinoma of no special type (ductal) (1 case). A morphologic transition from MGA to AMGA to carcinoma was observed in all cases. S100 was consistently positive in all cases. Myoepithelial markers demonstrated the absence of myoepithelial cells in the invasive carcinoma as well as MGA / AMGA component. Conclusion This series highlights the histologic spectrum and key diagnostic features of MGA-associated carcinoma. Awareness of this entity is crucial for appropriate diagnosis and clinical management.

Abstract Introduction/Objective Cervical cancer remains a global health concern, with significantly higher incidence in countries like Peru compared to the U.S. Cytopathology plays a vital role in early detection and prevention, making it an important area of focus for aspiring pathologists. Methods/Case Report A medical student with an interest in pathology participated in a global health rotation in Cusco, Peru, at CerviCusco, a nonprofit clinic dedicated to cervical cancer care. Under the guidance of a trained cytotechnologist, the student engaged in hands-on cytopathology work, including processing and screening SurePath (Franklin Lakes, NJ) slides, and reviewing abnormal cases. The student had access to a microscope and dedicated time developing microscopy skills and learning cervical cytomorphology, with emphasis on identifying significant abnormalities. Results NA Conclusion This experience demonstrates the educational value of incorporating global health electives into medical training, especially in resource-limited settings with high disease burden. Exposure to such environments enhances foundational diagnostic skills and fosters an early appreciation for global health disparities. Expanding similar opportunities can enrich pathology education and inspire future contributions to international health efforts.

Abstract Quantifying urine protein is critical for detecting and monitoring kidney disease. However, screens for proteinuria are unable to detect low levels of albuminuria. For this reason, our institution has long measured urinary total protein and osmolality on routine urinalysis specimens (RUS) and calculated a predicted 24-hour protein excretion (PER) based upon the protein to osmolality ratio (POR). Within the last decade, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been approved by the United States Food and Drug Administration (FDA) as a treatment for adults with type 2 diabetes mellitus, and these agents appear to be beneficial for many forms of proteinuric renal disease and confer renal protection. Therefore, we investigated whether the expected glucosuria and increase in urine osmolality while on SGLT2i would significantly alter the POR, and hence predicted PER, via a retrospective analysis of residual timed and randomly collected urine specimens. Between January 1st, 2014, until January 29th, 2025, 5820 patients with nearly contemporaneous (collected within one week of each other) timed collections and RUS were identified that included 5656 not on SGLT2i (Cohort A) and 164 patients prescribed SGLT2i (Cohort B). Total protein concentrations were assessed using a Roche Cobas c701 by using benzethonium chloride. The osmolality was determined via freezing point depression using a Precision Systems Inc Multi-OSMETTE, whereas glucose measurements were made using either an Arkray AX-4030 with AUTION Stick 9EB test strips or a Clinitek Status with Multistix 10 SG reagent strips. Predicted 24-hour protein results were then calculated from the POR using a published formula based upon prior clinical studies: 10(x·[log(protein/osmolality)]+y where x is 0.908 or 0.953 for males and females, respectively, and y is 2.8254 or 2.9739 for males and females, respectively. In Cohort A, there was good correlation between the predicted and measured 24-hour PER (Spearman correlation coefficient, ρ = 0.78), although the predicted PER underestimated the measured PER (Passing-Bablok regression, y = 1.54x-20.97 mg/24 hr). Importantly, a strong correlation (ρ = 0.93) and similar distribution (p=0.17) were found between the predicted and measured PER in Cohort B, with a much-reduced proportional bias (y = 1.06x+62.96 mg/24 hr). Furthermore, comparison of the difference between the predicted and measured PER between the two cohorts demonstrated the same prediction accuracy (p = 0.65), with a median difference (interquartile range) of 79 mg/24 hr (256) and 109 mg/24 hr (480) for Cohort A and B, respectively. Finally, a strong correlation (ρ = 0.85), similar distribution (p = 0.23), and little bias (y = 0.96x+28.14 mg/24 hr) existed between the predicted and measured PER for all patients with overt glucosuria (urine glucose ≥1000 mg/dL, n = 348). In summary, these data suggest that the established formula for predicted PER on RUS is equally valid for patients on or off SGLT2i, and that this result is a useful clinical estimating tool.

Abstract Introduction/Objective Burnout among trainers can lead to increased human-derived laboratory errors (HDLEs), which can negatively affect patient outcomes. Through implemented improvement strategies, trainer burnout and HDLEs were reduced without impacting the trainee burnout by creating a core training group to ensure consistency in training and providing additional training tools. Methods/Case Report Burnout was assessed using a survey from the Burnout Assessment Tool1. This survey indicates burnout as a numerical score and was given to trainers and trainees at 3 intervals. Pre-implementation concluded trainer burnout average score was 2.47. HDLEs were categorized and totaled in conjunction with the burnout surveys. Pre-implementation data for HDLEs showed 14% were associated with a training event and 14% were associated with a process change that did not have a training event. Results: Conclusion Final data showed a decrease in average burnout score for trainers (pre=2.47, post=2.26). Trainee score was not statistically different. Post-implementation data of HDLEs showed 6% were associated with a training event and 0% were associated with a process change that didn’t have a training event. In review of the project, standardization of training, proper communication of process changes decreases average burnout of trainers and reduces the amount of HDLEs associated with training and process changes.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented. Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair. Study Design: Prospective cohort study; Level of evidence, 2. Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 were selected. Six-year follow-up was obtained to determine whether any subsequent surgery had occurred since their initial revision ACLR. If so, operative reports were obtained, whenever possible, to verify pathological condition and treatment. Results: In total, 221 patients from 1234 revision ACLRs underwent concurrent primary meniscal repairs (18% of the cohort). There were 238 repairs performed: 173 medial and 65 lateral. The majority of these repairs (n = 181; 76%) were performed with an all-inside technique. Six-year surgical follow-up was obtained in 77% (171/221) of the cohort, or 189 of 238 (79%) of the repairs (136 medial, 53 lateral). The meniscal repair failure rate, defined as reoperation, was 16% (31/189) at 6 years. Of the 31 failures, 28 were medial (24 all-inside, 4 inside-out; 28/136 = 20.6% failure rate) and 3 were lateral (2 all-inside, 1 inside-out; 3/53 = 5.7% failure rate). Three medial failures were treated in conjunction with a subsequent repeat revision ACLR. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears (20.6% vs 5.7%; P = .01) and had a significantly shorter survival time compared with lateral tears ( P = .02). No difference was found between the failure and nonfailure groups when it came to tear type, tear length, repair technique utilized, suture/implant type, or number of sutures used between the 2 groups. Conclusion: Meniscal repair in the revision ACLR setting has a 16% failure rate at 6 years. Failure rates for medial tears (20.6%) were found to be higher than that for lateral tears (5.7%), which aligns with previous studies in both the revision and primary ACLR setting.

ABSTRACT Solid tissue‐derived extracellular vesicles (ST‐EVs) are extracellular vesicles (EVs) separated directly from solid tissues of both vertebrates and invertebrates. ST‐EVs provide a physiologically relevant snapshot of tissue‐specific molecular dynamics and can be enriched directly in situ, from tissues in their natural state, preserving the native characteristics of ST‐EVs. However, their enrichment presents unique technical challenges compared to EVs derived from biofluids or cell culture media. The need for transparent reporting in ST‐EV research is crucial to enhance the reproducibility, comparability, and reliability of research findings. The Solid Tissue Task Force, part of the Scientific Reproducibility Subcommittee of International Society for Extracellular Vesicles, aims to recommend reporting parameters and identify outstanding questions related to the pre‐analytical and analytical handling of solid tissues, as well as ST‐EV separation and characterization. These steps are essential for advancing the understanding of the biological roles of ST‐EVs and their potential clinical applications.

Background Transthyretin amyloid cardiomyopathy (ATTR‐CM) has a specific pathophysiology, with myocardial stiffening and systolic dysfunction only in advanced stages. We aimed to investigate the response to cardiac resynchronization therapy (CRT) in ATTR‐CM compared with heart failure. Methods In this multicenter, observational study, patients with ATTR‐CM receiving CRT (n=101) were matched to patients without amyloid cardiomyopathy by sex, age, and implantation type (CRT with versus without defibrillator versus conduction system pacing, upgrade versus first implant). We evaluated changes in QRS duration and echocardiographic parameters following CRT implantation and at the most recent available assessments. The study end points were all‐cause death alone or combined with heart failure hospitalization. Results Patients with ATTR‐CM (median age, 76 [interquartile range, 72–83] years, 98% men, left ventricular (LV) ejection fraction 30% [26–33]) showed greater QRS shortening after CRT implantation ( P =0.012), but not after a median of around 1 year ( P =0.152). There were no significant differences in the absolute LV ejection fraction changes immediately after implantation (+7 [+2/+10] versus +3 [0/+9] units; P =0.124), or to the last echo ( P =0.796), which was performed after 1.3 years in patients with ATTR‐CM and 2.9 years in patients without amyloid cardiomyopathy. Patients with ATTR‐CM had a shorter survival than controls ( P <0.001 for both end points). Patients with ATTR‐CM experiencing an early improvement in LV ejection fraction had a longer survival (log‐rank, 4.3; P =0.038). Conclusions Following CRT implantation, patients with ATTR‐CM show QRS narrowing and improvement in LV ejection fraction, not different from patients without amyloid cardiomyopathy. Early favorable LV remodeling seems to be associated with a lower risk of all‐cause death.

Abstract Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of liquid tumors but faces many challenges against solid tumors including T cell exhaustion and poor CAR durability. Here, we show that engaging the CAR T cell endogenous TCR using an oncolytic virus (OV) enhances CAR T cell functionality, durability, and therapy. Upon combination therapy of solid tumors with CAR T cells and vesicular stomatitis virus (VSV), a subpopulation of antiviral, TCR-primed CAR T cells was generated with enhanced effector functions, altered activation states, and differential gene and protein expression when compared to CAR T cells that do not undergo TCR priming. Single cell RNA-sequencing showed clonal expansion of anti-VSV CAR T cells, selective avoidance of exhaustion, and enhancement of effector-associated genes with VSV-mediated CAR T cell expansion. CD4 T cells played a pivotal role in both the generation and polarization of these TCR-primed CAR T cells. These results provide a strong rationale both for a novel use of intravenous administration of oncolytic viruses with separate applications from their direct oncolytic activity and for directly exploiting the TCR and its endogenous interactions as tools for fine tuning the phenotype and function of CAR T cells, with particular efficacy against solid tumors.