Citations

PURPOSE The feasibility of Oncotype DX Breast Recurrence Score testing on diagnostic core needle biopsy (CNB) samples has been demonstrated through analysis of a large central laboratory experience. However, concordance with paired samples from the same primary breast tumor has not been comprehensively evaluated. The primary objective of this study was to determine the degree of concordance of Recurrence Score (RS) results between paired CNB and surgical excision (SE) specimens from the same untreated primary breast tumor of patients with early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative invasive breast cancer. MATERIALS AND METHODS Patients with a clinical RS result on either a CNB or SE specimen were included. Lin concordance correlation coefficient (CCC) with 95% CIs was estimated to assess agreement of continuous RS results between paired samples. Cohen Kappa with 95% CIs was used to evaluate categorical RS result concordance. RESULTS A total of 134 patients were identified with paired CNB and SE specimens. The median age was 62 years (range, 33-99; 23 patients [17%] were age ≤50 years v 111 [83%] age >50 years). The mean RS results were 15.6 (range, 0-56) for CNB and 16.6 (range, 0-59) for SE ( P = .003), with no statistically significant differences in RS categories. Agreement between continuous RS results from paired samples was strong, with a Lin CCC of 0.86 (95% CI, 0.80 to 0.90). The overall percent agreement in RS categories was 91.8% (95% CI, 87.1 to 96.4). Categorical agreement was further supported by a Cohen Kappa statistic of 0.64 (95% CI, 0.44 to 0.83), indicating substantial agreement between CNB and SE specimens. CONCLUSION The results of this study demonstrate high concordance of RS results between paired samples, which supports the use of CNB for Oncotype DX testing.

Abstract Women remain underrepresented in physical medicine and rehabilitation, comprising only 36%–39% of residents despite evidence that diverse teams improve patient outcomes. Limited early exposure and systemic barriers may contribute to this disparity. In this cross-sectional study, we surveyed 1101 US premedical students from 198 colleges across 40 states and territories to assess perceptions of physical medicine and rehabilitation and identify effective early intervention strategies. While respondents included all gender identities, the analysis focused on the 870 female-identifying students (78.8%) due to the study’s primary aim of addressing gender equity in physical medicine and rehabilitation. Only 30.6% were familiar with physical medicine and rehabilitation, with exposure primarily through social media (42.6%) and personal connections (31.1%); just 9.0% had shadowed a physical medicine and rehabilitation physician. Financial concerns were prevalent, with 68.6% citing medical education costs and 66.4% citing application fees as deterrents. Despite these barriers, 60.6% expressed interest in learning more about physical medicine and rehabilitation. Preferred engagement strategies included shadowing (81.8%), interactive workshops (76.6%), mentorship programs (60.1%), and gender-specific events such as “Women in PM&R” (62.8%). These findings underscore the need for targeted, early outreach initiatives that address both informational and financial barriers, aiming to foster greater awareness and representation of women in physical medicine and rehabilitation and ultimately support a more inclusive physician workforce.

Traumatic brain injury (TBI) is one of the leading causes of death and neurological disability worldwide. The search for biomarkers that indicate TBI severity and prognosis with greater accuracy is ongoing. This study aimed to evaluate the significance of several neuroinflammatory cytokines and chemokines, assessing their potential as biomarkers in pediatric TBI (pTBI). This was an exploratory analysis of inflammatory cytokines and chemokines measured in a subset of 26 children aged 0–18 years with TBI and 21 controls. TBI severity was determined by GCS. The functional outcome was measured via the GOS-E score at 6 weeks and 3, 6, 9, and 12 months post-injury. Serum samples were analyzed for ICAM-1, VCAM-1, SAA, CRP, IFN-g, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8, TNF-a, TNF-b, eotaxin, eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1a, MIP-1b and TARC. Levels of IL-6, IL-10, IL-13, IL-16, MDC, and GM-CSF were increased, and IFN-γ, IL-5, IL-8, and eotaxin-3 were decreased at enrollment when compared with controls. Elevated IL-6 and IL-10 at enrollment were associated with severe TBI (AUC of 1, p = 0.0002 and p = <0.0001, respectively). IL-6, IL-10, IL-16, and TNF-β at enrollment and IL-5 at 24 h were elevated in children with unfavorable outcomes, with an AUC > 0.8, suggesting biomarker potential. Our data indicate that several cytokines and chemokines measured after TBI may aid in the assessment of pTBI severity and prognosis. IL-6, IL-10, and IL-16 may show potential as biomarkers for pTBI severity and outcomes.

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer (SITC) previously published two articles providing best practice guidelines for mIF/IHC staining, image analysis, and data sharing. Here, SITC convened stakeholders to develop the third article in the series, a consensus checklist for scientific reporting of mIF/IHC data to support and complement the best practice guidelines. The checklist includes critical components of mIF/IHC applications to be defined within publications such as detailed descriptions of analytical validation; image acquisition, selection, and registration methods; and cell clustering and spatial analysis strategies, amongst others. Such information will help with data reproducibility and comparison across studies towards future drug and assay development.

Abstract Context Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. Objective This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. Methods The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. Results At week 38, lonapegsomatropin significantly reduced trunk percent fat (−1.68% vs +0.37%; least squares [LS] mean difference −2.04%; P &lt; .001), increased total body lean mass (+1.60 kg vs −0.11 kg; LS mean difference 1.70 kg; P &lt; .0001), and reduced trunk fat mass (−0.48 kg vs +0.22 kg; LS mean difference −0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. Conclusion The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.

Abstract The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer’s disease to explore the brain asymmetry within the Alzheimer’s disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and APOE ε4 status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer’s disease progression in autosomal dominant Alzheimer’s disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

An ST-segment elevation myocardial infarction is a life-threatening condition within the spectrum of acute coronary syndrome, with well-recognized implications for short-term and long-term health outcomes. Retrospective review of our institutional electronic health records identified patterns of inaccurate acute coronary syndrome diagnostic assignment, including the presence of erroneous ST-segment elevation myocardial infarction diagnoses in discharge records. Such erroneous diagnoses in the durable health record may increase risk to patients through inadequate risk assessment and inappropriate follow-up care. Misapplication of a shortcut in our electronic health record system for rapidly ordering emergent cases was identified as a potential cause of the quality gap. To address this issue, a nurse-led quality improvement project was developed by using the define, measure, analyze, improve, and control framework. The project intervention decreased the percentage of patients with erroneous diagnoses from 24% to 7% and marginally improved nursing staff satisfaction. Our project successfully addressed an institutional quality concern. Our goal of reducing erroneous discharge diagnoses with minimal disruption to our existing practice was achieved, positively affecting our patients. Including both nurse leaders and frontline health care workers ensured the success of our project.