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Abstract Context Point-of-care ultrasound (POCUS) has diverse applications across various clinical specialties, serving as an adjunct to clinical findings and as a tool for increasing the quality of patient care. Owing to its multifunctionality, a growing number of medical schools are increasingly incorporating POCUS training into their curriculum, some offering hands-on training during the first 2 years of didactics and others utilizing a longitudinal exposure model integrated into all 4 years of medical school education. Midwestern University Arizona College of Osteopathic Medicine (MWU-AZCOM) adopted a 4-year longitudinal approach to include POCUS education in 2017. There is a small body of published research supporting this educational model, but there is not much data regarding how this approach with ultrasound curriculum translates to real-world changes in POCUS use by graduate student clinicians having received this model of education. Objectives The objectives of this study are to determine the frequency of POCUS use by MWU-AZCOM graduates and to assess how a 4-year longitudinal ultrasound curriculum may enhance the abilities of MWU-AZCOM graduates to perform and interpret ultrasound imaging in specific residency programs. Methods The study was approved by the MWU Institutional Review Board (#IRBAZ-5169, approval date October 3, 2022). An anonymous novel 12-question survey was conducted utilizing Research Electronic Data Capture (REDCap), a secure online platform, and distributed to MWU-AZCOM 2021 and 2022 graduates via email. Survey questions were aimed at assessing frequency of use, utilization of different imaging modalities, reasons for utilizing POCUS, barriers/enablers to utilizing POCUS, ultrasound training, and confidence in performing scans and interpreting POCUS imaging. All of the 104 surveys returned were included in the study. Statistical software R version 4.3 was utilized to conduct statistical analyses. Results Of the 484 surveys distributed, 104 were completed (21.5 % response rate). Responses came from residents working in 14 different specialties, 50 in primary care and 54 in nonprimary care. Of all respondents, 85.6 % currently utilize POCUS in their practice on at least a monthly basis and 77.0 % believe that their POCUS training in medical school enriches their current practice in residency. The top five modalities utilized by residents were procedures (89.9 %), cardiac (88.8 %), pulmonary (82.0 %), Focused Assessment with Sonography for Trauma (FAST, 73.0 %), and vascular (71.9 %). Respondents recognized POCUS as a beneficial diagnostic tool (97.8 %) and reported enhancements in physical examination skills (58.4 %) and professional growth (61.8 %). Facilitators for POCUS adoption included cost-effectiveness (82.0 %), diagnostic differentiation (78.7 %), and safety (79.8 %). Barriers included a lack of trained faculty (27.9 %), absence of necessary equipment (26.9 %), and cost of equipment (22.1 %). Participants demonstrated high confidence levels in performing (74.0 %) and interpreting (76.0 %) POCUS, with 43.3 % believing that their POCUS training enhanced their attractiveness as residency candidates. Conclusions This study supports the positive impact of a 4-year longitudinal POCUS curriculum on graduates’ practice. It emphasizes the link between MWU-AZCOM’s curriculum and real-world clinical needs. Addressing identified barriers and advancing hands-on training can further enhance POCUS understanding, ensuring that future physicians are well-prepared to leverage its diagnostic potential across medical specialties.

AbstractBackgroundAlthough the rate of Alzheimer’s disease (AD) in African‐ancestry (AA) Americans is higher than that of persons from European‐ancestry (EA) populations, AA participants have been underrepresented in AD neuropathological studies.MethodUtilizing the AD Research Centers (ADRC) infrastructure, we obtained AA donor pre‐frontal cortex (PFC) tissue from brain repositories of 12 ADRC and generated bulk RNA sequencing (RNA‐seq) data for 179 samples that met QC and inclusion criteria. Previously generated PFC RNAseq data were obtained for 28 additional AA donors from the Columbia University ADRC. Differential gene expression was evaluated among 125 donors with a neuropathological diagnosis of AD (NIA‐Reagan intermediate or high likelihood) and 82 neuropathologically confirmed controls using regression models including covariates for age at death, sex, cell‐type frequencies, and RNA integrity number (RIN) calculated with Limma. FDR‐corrected p‐values (padj) were calculated to control for the 33,611 genes examined.ResultA total of 482 genes surpassed the multiple‐testing threshold. The most significant, ADAMTS2 (p = 2.96 × 10‐8, padj = 0.001), showed increased expression in AD cases (see Table/Figure). We note that ADAMTS2 was differentially expressed in a prior EA study of neuropathologically confirmed AD cases and controls (Panitch et al. Molecular Psychiatry 2021). Additionally, a recent analysis of cognitive resilience in EA neuropathological AD cases identified a strong association with ADAMTS2 (See Li et al. AAIC2024 abstract). Of the differentially expressed genes observed in the Panitch et al. EA study, 385 (35%) were nominally significant,65 (5.8%) were corrected significant, and most (89%) of these genes had the same effect direction in the AA cohort. Some of the observed associations appear to be AA specific (e.g., EFR3B, IRS4, and CA12; see Table). Additionally, we found nominally significant (p<0.05) associations with expression of APOE (Log2 fold change [L2FC = ‐0.20, p = 0.012) and several other established AD genes including SORL1 (L2FC = ‐0.10, p = 0.014) and IGF1R(L2FC = 0.11, p = 0.0013).ConclusionThis largest‐ever (to our knowledge) gene expression study of AD in postmortem brain tissue from AA donors implicates many more genes as having a role in AD in this population than previously identified in genome‐wide association studies and provides insight into trans‐ancestry differences risk for AD.

Introduction: Trust and rapport between patients and physicians form the cornerstone of effective medical practice. A key factor influencing this trust is the patient’s perception of the physician’s appearance. Women physicians often face more rigorous expectations concerning their physical appearance compared to men physicians, creating a need to balance traditional professional attire with maintaining femininity and individuality. This review explores the unique challenges women physicians encounter in presenting a professional image. Methods: A narrative review was conducted using PubMed and Google Scholar to identify studies addressing both patient and physician perceptions of physician appearance. The search was limited to studies conducted in the United States and published between 2004 and 2024. Seven articles met the inclusion criteria and were selected for analysis. Results: The findings suggest that professional attire, particularly when combined with a white coat, is associated with higher perceptions of competence and professionalism. However, women physicians face ambiguity in meeting these expectations compared with men. In addition, women are more frequently mistaken for nurses, phlebotomists, or support staff based on their attire and appearance. Discussion: Overall, patients tend to prefer professional attire to physicians, but these preferences are influenced by cultural, demographic, and age-related factors. Women physicians, in particular, experience heightened scrutiny regarding their appearance and are subject to stricter norms than men physicians. This challenge is further amplified for young women trainees, who may struggle to convey professionalism due to their youthful appearance.

Background: The purpose of this study was to report on 2-year results of vertebral body tethering (VBT), performed under a Food and Drug Administration protocol, to obtain insight into outcomes and complications. Methods: Forty prospectively enrolled patients with adolescent idiopathic scoliosis (AIS) who had a Sanders score of ≤4 or a Risser score of ≤2 underwent VBT for curves between 40° and 70°. Surgical, radiographic, and patient-reported outcomes were reviewed at a minimum 2-year follow-up. Results: Mean age at surgery was 13 (range, 10 to 16) years. The 40 patients were 90% female; 95% White, 2.5% other, and 2.5% unreported; and 92.5% non-Hispanic, 5% Hispanic, and 2.5% unreported. A mean of 8 (range, 5 to 12) levels were instrumented. Most patients were at Sanders 4 (65%) and Risser 0 (63%). Mean length of stay was 3 ± 1 days, estimated blood loss was 236 ± 158 (range, 25 to 740) mL, and operative time was 4.4 ± 1.4 hours. Mean correction of the major curve was 44% (range, 22% to 95%) on the 3-month standing radiograph, 49% at 1 year, and 46% (range, −10% to 93%) at 2 years. The mean major Cobb angle improved from 51° ± 8° (range, 40° to 70°) preoperatively to 27° ± 11° (range, 3° to 56°) at 2 years. Success at 2 years, defined by a Cobb angle of <35° and no reoperation, was seen in 30 patients (75%) and was associated with a mean Cobb angle of <35° on the first postoperative standing radiograph (p < 0.001). Twelve patients (30%) demonstrated improvement in the curve with growth. By 2 years, 2 (5%) of the patients underwent repeat surgery (1 release for overcorrection, 1 lumbar VBT for lumbar curve progression after thoracic VBT). The Scoliosis Research Society (SRS) satisfaction score improved 2 years following surgery (p < 0.001), but other SRS domains only remained stable over time. Beyond 2 years, 1 additional lumbar tether was required after thoracic VBT, 1 implant was removed, and 3 fusions were performed, for a 10% fusion rate and overall 20% reoperation rate at a mean of 3.8 ± 1.1 years of follow-up. The rate of cord breakage in the study population was 20%. Conclusions: In skeletally immature patients treated in the U.S. under a prospective Investigational Device Exemption, there was a 75% rate of successful outcomes at 2 years. Most correction was obtained at the time of surgery, and inadequate intraoperative curve correction was associated with a higher Cobb angle on the first postoperative standing radiograph and failure by 2 years. Level of Evidence: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Introduction: The Mindfulness-Based Stress Reduction program for breast cancer survivors (MBSR [BCs]) is a stress-reducing program designed to increase cognitive functioning through four meditational practices. This randomized clinical trial aimed to determine if improvements in cognitive functioning and perceived cognitive abilities achieved from the MBSR(BC) were mediated through increased mindfulness, decreased rumination, and decreased perceived stress. Methods: Breast cancer survivors (BCSs) who met inclusion criteria of stage I, II, or III BC and received either chemotherapy (CT) or both CT and radiation were randomized to either the 6-week MBSR(BC), or Breast Cancer Education Support (BCES) program, or to a usual care (UC) regimen. Analysis of covariance was first implemented to identify potential mediators, followed by a formal mediational analysis to evaluate the effects of MBSR(BC) on 6-, 12-, and 26-week outcomes. Results: After consent, 212 BCS were randomized to MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31). The mean age was 56.5 and the majority of the BCS, 73.1%, were White and non-Hispanic. Results showed increases in “observing” as part of mindfulness as a potential mediator of MBSR(BC) effects on impairments on quality of life and logical memory at 6 months relative to UC. No mediation effects were identified for outcomes measured at 6 or 12 weeks and also when MBSR(BC) was compared with the BCES program. Discussion: These results partially supported our hypothesis that improvement in cognitive functioning would occur through increased mindfulness. Although few mediating relationships were identified, results showed a relationship between mindfulness and cognitive functioning. Both mediating relationships occurred through increases in “observing,” a subconcept of “mindfulness,” when compared to the MBSR(BC) with UC at 6 months. This study shows that mediators may help “optimize” clinical therapeutic treatment effects, thus contributing to the advancement of science. Trial Registration: ClinicalTrials.gov, www.ClinicalTrials.gov . Registration Number: NCT02786797.

Background: Controversy exists around the optimal timing of resection of nevus sebaceous (NS). The authors aim to determine optimal timing of NS resection and identify predictors of surgical outcomes and secondary intralesional neoplasms. Methods: Retrospective chart review of all patients with biopsy-proven NS diagnosis treated at the authors' institution between 1987 and 2024. Results: A total of 632 patients (317 females) underwent biopsy at a median age of 17 (interquartile range 11.7–36.9) years. Benign secondary intralesional neoplasms were found in 67 (10.6%) patients, with syringocystadenoma papilliferum being the most common. Malignant secondary intralesional neoplasms were diagnosed in 62 (9.8%) patients, with basal cell carcinoma being the most common. The incidence of secondary intralesional neoplasms was 3.9%, 24.4%, 36.05%, and 54%, in patients aged 0 to 20, 20 to 40, 40 to 60, and 60 to 80 years, respectively (P<0.001). Age and NS area were associated with an increased risk of developing benign and malignant intralesional neoplasms (P=0.01). Younger patients were more likely to need general anesthesia for excision (median age 10.42 versus 17 years, P<0.001). Surgical complications occurred in 10 cases, and 6 patients required unanticipated revision surgery. The risk of developing secondary intralesional neoplasms was similar across different NS anatomic regions (log-rank, P=0.09). Conclusion: Surgical excision of NS is safe and has an acceptable risk profile. The findings of this study support our historic practice of NS excision before puberty (before the accelerated growth phase) to reduce the risk of developing secondary intralesional neoplasms.

Purpose: To review cases of lateral brow dermoid cysts and gain insight into the utility of preoperative imaging, incidence of intraorbital extension, and recurrence rate. Methods: This is a retrospective study of all patients who underwent excision of lateral brow dermoid cysts at the authors' academic center over a 37-year period. Results: A total of 136 patients were included. The median age at presentation was 5.6 months [interquartile range (IQR) 3–16.5], and the median age at removal was 1.5 years (IQR 0.9–3.4). Preoperative imaging was performed in 44 patients. Intraorbital communication was predicted in 4 patients who underwent imaging and confirmed in 6 patients (4.4%) intraoperatively. Superficial dermoids were the most common depth (n=79, 58.1%), followed by periosteal (n=37, 27.2%) and intraosseous (n=14, 10.3%). Two patients (1.4%) presented with postoperative hematoma that required surgical evacuation. Recurrence was seen in 2 patients (1.4%). Among those who completed a follow-up, the median follow-up time was 1 month (IQR 0.44–5.8 months). Conclusion: The authors' study revealed that the majority of lateral brow dermoid cysts are either superficial or involve the periosteum, with orbital involvement being rare. None of our patients demonstrated intracranial communication. Imaging did not seem to add clinical value in patients for whom there was no clinical suspicion for the involvement of the deeper tissues, so careful consideration of ordering preoperative imaging would help decrease health care costs and avoid radiation exposure, which is particularly concerning for pediatric patients. The recurrence rate of lateral brow dermoid cyst seems to be low but studies with longer follow-ups are needed.

Background: Venetoclax (Ven), a BCL2 inhibitor, has shown promising responses in multiple myeloma (MM) patients with t(11;14) and/or BCL2 expression. However, consistent benefit in clinical trials remain elusive. This report evaluates the efficacy and safety of Ven combination therapies, including in the non-t(11;14) subgroup, and examines the impact of secondary cytogenetic abnormalities (SGA) on outcomes. Methods: This retrospective study included multiple myeloma (MM) patients without concurrent AL amyloidosis treated with Ven-based combinations at Mayo Clinic sites from January 2015 to December 2023. FISH data was collected at diagnosis and before venetoclax initiation to assess SGAs. Refractoriness was defined by progression on or within 60 days of stopping treatment. Patients refractory to at least one proteasome inhibitor (PI), immunomodulatory drug (ImiD), and anti-CD38 antibody were considered triple-class refractory (TCR). Ven combinations were grouped as: Daratumumab/CD38 antibody (Dara)-Ven based if received Dara ± other drugs, PI-Ven-based without Dara, Ven-dexamethasone (Ven-d), and other combinations (Ven-Misc). BCL2 expression in patients without t(11;14) was determined by immunohistochemistry (IHC). Progression-free survival (PFS) was calculated from treatment initiation to disease progression or last follow-up. Results: We included 232 patients in this study. The median age at diagnosis of MM was 62 years (range 32-87), and the median age at initiation was 68 years (range 35-89). The median time from diagnosis of MM to initiation of Ven was 55 months (95% CI 28, 89 months), and the median follow-up from initiation of Ven-based treatment was 17.2 months (95% CI: 14, 22). Patients had received a median of 3 lines (IQR 4-6); 65% (n=152) of patients were TCR, 71% (n=163) had received autologous stem cell transplant and 7% (n=16) patients had received prior immune effector therapy prior to initiation of Ven-based therapy. The majority (83%, n=190) of the patients harbored a t(11;14); in the patients without t(11;14), a BCL2 expression by IHC was tested in 18 patients and positive in 17 patients. The most common Ven-based combinations included: Dara-Ven-d (19%, n=44), PI-Ven-d (30.2%, n=70), Ven-d (48.3%, n=112), Ven-misc (2.6%, n=6). The overall response rate for the entire cohort was 57% [64% for t(11;14) and 26% for non t(11;14), p&lt;0.0001]. The median PFS for the entire cohort was 9.5 months (95% CI 8.5,13), and the duration of response was 18 months (95% CI 15.2-23.3). The median PFS was 11.8 months (95% CI 9.5-16.7) for patients harboring a t(11;14) compared to 2.9 months (95% CI 1.8, 8.4) for patients without a t(11;14), p&lt;0.0001. Among the non-t(11;14) cohort with BCL2 expression, the median PFS was 1.8 months (95% CI: 1.2-4.2). Among the 190 patients with t(11;14), 18% (34/190) harbored deletion 17p and 32% (60/193) harbored a 1q gain/amplification (referred hereforth as 1q21+) at initiation of Ven-based therapy. In the cohort of patients with t(11;14), the presence of either del17p or 1q21+ (n=85/190) was associated with a significantly inferior PFS [median PFS 8.2 months (95% CI: 5.5,13)] vs. 15.1 months (95% CI: 11.6, 22), p=0.03. At the last follow-up,42 patients had ongoing treatment with ven-based combination. Most common reasons for discontinuation were progression (77% N=140), adverse effect (12%, n=22), patient/provider preference(9%, n=17); 2% (n=4) patients died without progression (3 infection, 1 unclear). The most commonly utilized maximum dose of venetoclax was 400 mg (42%); 15% (n=35) of patients required a dose reduction, and 23% (n=54) received a ramp-up. Tumor lysis syndrome was not noted in any patient. Infectious complications were noted in 23% (n=52). The estimated median OS from initiation of ven-based Rx was 34 months (95%CI 25-47). The estimated median OS for patients without a t(11;14) was 6.2 months (95% CI: 3.3-11.3) compared to 46 months (31.4-54.1), p&lt;0.0001. In the t(11;14) subgroup, the 18-month OS rate was 79% for patients without 1q21+/del17p vs. 50% for patients with a 1q21+/del17p (p=0.002). Conclusion: Venetoclax-based regimens represent an important treatment option for patients harboring a t(11;14). The PFS in patients with BCL2 expression without t(11;14) was poor suggesting lack of efficacy of venetoclax-based regimens for that subgroup. Presence of concurrent del17p and/or 1q21+ with t(11;14) portends an inferior PFS.

Introduction: In recent years, multiple myeloma (MM) research has increasingly focused on unraveling the complex interactions between malignant plasma cells and their surrounding bone marrow microenvironment (BMME). To further elucidate these interactions, we developed a comprehensive single-cell atlas of the MM BMME, integrating both coding and noncoding (ncRNA) transcriptional profiles. By correlating these profiles with specific cytogenetic abnormalities in myeloma cells, we aim to uncover how ncRNAs regulate the phenotypic and functional states of myeloma cells and, consequently, shape the cellular landscape of the BMME. A detailed understanding of how the noncoding transcriptome affects the cellular components and immune landscape of the BMME is essential for advancing our knowledge of MM pathogenesis and identifying novel biomarkers and therapeutic targets. Methods: Our atlas was constructed using single-cell RNA sequencing data from 481 samples of CD138neg cells sorted from bone marrow aspirates of MM patients enrolled in the MMRF CoMMpass study. This dataset includes accompanying whole-genome sequencing and survival data, enabling correlative analysis between transcriptional profiles, cytogenetic abnormalities, and patient outcomes. To generate a combined coding and non-coding transcriptome, we developed an expanded human reference genome by systematically merging mRNA and ncRNA transcripts from the LncBook2.0 and GENECODEv42 reference genomes. The sequencing data was aligned to this expanded genome, followed by quality control processing, batch correction, clustering, and supervised analysis. Results: The resulting coding and non-coding atlas comprises over 1.9 million cells, spanning immune, plasma, and stromal compartments. Remarkably, ncRNAs constituted 46% of the associated genes, including 22,102 long ncRNAs (lncRNAs) and 3,112 small ncRNAs. Subclustering analysis of the major immune compartments (B lymphoid, myeloid, and NK and T lymphoid) yielded 70 subclusters, with ncRNAs representing 24-38% of the top 100 differentially expressed genes within each compartment. This underscores the significant role of ncRNAs in distinguishing immune subpopulations. Moreover, examining the association between specific cytogenetic abnormalities and the immune composition of the BMME, 30 subclusters were found to be differentially abundant (P &lt; 0.05) between cytogenetic abnormalities, supporting our hypothesis that myeloma cell genotypes significantly shape the immune microenvironment. For instance, patients with CCND1 amplification displayed an increase CD4+ central memory T cells with a decrease in CD8+ cytotoxic T cells. Similarly, patients with 1q21 gain exhibited an increase in TGFβ-stimulated monocytes, while a decrease in cytotoxic CD8+ T and CD56dim NK cells was observed in patients with 17p13 deletion. Next, examining which ncRNAs are associated with specific cytogenetic abnormalities, we identified 14 ncRNAs significantly differentially expressed across cytogenetic abnormalities. Increased expression of six of these ncRNAs were associated with poor overall survival both independently and in combination (P &lt; 0.05, HR = 3.7). Notably, three of these ncRNAs have documented roles in cancer progression but have not been previously studied in the context of MM. Subsequently stratifying patients based on their enrichment of these outcome-associated ncRNAs revealed even stronger associations with immune composition, including an increase in CD4+ regulatory T cells (P &lt; 0.05). This further supports our hypothesis that myeloma cell genotypes shape the BMME. Lastly, by constructing a gene regulatory network to predict the interactions between coding and noncoding RNAs, we illustrate the regulatory networks of ncRNAs modulating the phenotypes of myeloma and immune cell subpopulations. Conclusion: In summary, we present the first high-resolution transcriptomic atlas of the MM BMME, integrating both coding and noncoding RNAs. This study reveals distinct immune subpopulations associated with specific myeloma cell genotypes and highlights the central role of ncRNAs in modulating the phenotypic and functional states of both malignant and non-malignant cells in the MM BMME. Our findings emphasize the potential of ncRNAs as therapeutic targets and prognostic markers for MM, offering new avenues for research and clinical intervention.