Citations

Abstract This literature‐based systematic review and associated guidelines provide evidence‐based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. As is the standard, the previously described American Radium Society Appropriate Use Criteria methodology for this project was followed rigorously, with the Population, Intervention, Comparator, Outcome, Timing, and Study Design framework and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology to assess the evidence. RAND/University of California Los Angeles consensus methodology (modified Delphi) was used to rate the appropriateness of treatment options. Published between January 1, 2013, and July 16, 2025, 116 peer‐reviewed trials provided the evidence: 10 were well‐designed randomized phase 2/3 trials, 29 were moderately well designed trials that accounted for most common biases (matched cohort and phase 2), 76 trials had design limitations (retrospective), and one was a meta‐analysis. Clinical cases were created as examples to illustrate current acceptable management of LRRC. Treatment and prognosis are influenced by prior therapy and the site(s) and extent of LRRC. The ability to achieve a margin‐negative surgical resection is the ultimate determinant of survival and local control. Preoperative systemic therapy, radiation therapy, or a combination of the two can facilitate tumor downsizing and improve the likelihood of a margin‐negative resection. An individualized multidisciplinary approach is required to ensure the best outcome. Although this review does not suggest a major alteration of current practice, it provides reassuring evidence of the importance of combined‐modality therapy.

Background/Objectives: Thoracic aortic aneurysm (TAA) often results from structural degeneration of the aortic wall. Traditional management focuses on hemodynamic control using beta-blockers (BB) and angiotensin receptor blockers (ARBs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for diabetes and weight management, may offer additional vascular protective benefits through anti-inflammatory, antioxidative, and matrix-stabilizing mechanisms. However, their role in reducing mortality and thoracic aortic dissection (TAD) risk in patients with TAA has not been evaluated in human populations. In this study, we aimed to assess the association between GLP-1 RA use and the risks of mortality and thoracic aortic dissection. Methods: We conducted a retrospective cohort study of adults diagnosed with TAA between 2018 and 2024 across three Mayo Clinic sites. Patients receiving GLP-1 RAs were compared with non-users using 1:1 propensity score matching. Outcomes included all-cause mortality, cardiovascular mortality, and incident TAD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: A total of 32,279 patients with TAA, with a median age of 68.0 [IQR: 59.0–76.0] and 70.7% male, were included in a 1:1 propensity score match. This yielded a balanced cohort of 588 GLP-1 RA users and 588 non-users. Through a median follow-up of 4.1 (2.2, 5.9) years, GLP-1 RA use was associated with significantly lower 5-year cumulative incidence of all-cause mortality (5.0% vs. 14.5%, HR: 0.31; 95% CI: 0.19–0.50; p < 0.001), cardiovascular mortality (1.9% vs. 5.5%, HR: 0.30; 95% CI: 0.13–0.70; p = 0.005), and TAD (0.9% vs. 4.0%, HR: 0.19; 95% CI: 0.06–0.60; p < 0.0004). Conclusions: GLP-1 RAs are associated with reduced incidence of all-cause mortality, cardiovascular mortality, and TAD incidence in patients with TAA. Prospective studies are needed to confirm these findings and evaluate effects on aneurysm progression.

Abstract Exposure to asbestos is the primary cause of mesothelioma, however the processes underpinning its initiation and evolutionary trajectory remain elusive. To address this knowledge gap, we conducted whole exome sequencing and phylogenetic analysis of 277 mesotheliomas. Using multidimensional Dirichlet process clustering we inferred phylogenies, uncovering mutation order dominated by early 13q,1p, 8p, 6q and 22q somatic copy number alterations. Mesotheliomas exhibit a spectrum of genomic intra-tumor heterogeneity spanning linear (L) to highly branched (B) tree topologies, quantifiable by the Weighted Shannon Entropy (WSE). Somatic copy number alterations emerge earlier than single nucleotide variants (SNVs), and at a much faster relative rate in L-mesotheliomas. BAP1 is the only positively selected driver in L-mesotheliomas, whereas, B-mesotheliomas harbor multiple positively selected drivers and an aggressive phenotype, including a bias of loss of RPL5, and MTAP deletion linked to breakpoint enriched with long interspersed nuclear elements. L-trees had lower WSE, but greater T-cell inflammation and tertiary lymphoid structures, despite having a lower neoantigen burden. WSE is higher in larger volume, immunologically cold mesotheliomas, and is associated with shorter survival. In summary, progressive genomic heterogeneity is a defining feature of more aggressive mesothelioma yet illuminates opportunities for precision therapeutic intervention.

ABSTRACT Femoral nerve block is an essential regional anesthetic technique for surgery and analgesia of the anterior thigh, hip, and knee. Its effectiveness depends on understanding the femoral nerve's origin, branching pattern, fascial relationships, and common anatomical variations. This review summarizes current anatomical, cadaveric, and imaging studies to clarify the course of the femoral nerve and highlight variations such as high divisions, accessory branches, and vascular overlap that may influence block success. Approaches including landmark, nerve stimulator, and ultrasound‐guided techniques are reviewed with emphasis on procedural anatomy. Ultrasound features of the femoral nerve and fascia iliaca are correlated with cadaveric findings to outline optimal needle placement and spread of injectate. Continuous catheter methods, anesthetic selection, and volume considerations are also described. Comparative evidence indicates that ultrasound guidance improves accuracy, reduces vascular puncture, and decreases local anesthetic requirements compared with blind or stimulator‐based approaches. Clinical applications across orthopedic surgery, trauma care, and multimodal perioperative pathways are discussed, along with potential complications such as nerve injury, hematoma, systemic toxicity, and quadriceps weakness. Specifically, detailed knowledge of the femoral nerve's course beneath the fascia iliaca, its shifting proximity to the femoral vessels, and its variable early branching is the key to accurate needle placement, dependable block success, and fewer procedure‐related complications.

Tumor-associated antigens (TAAs) are non-mutated antigenic peptides expressed in cancer tissue at abnormally high levels but in normal tissue either at negligible levels, during only particular developmental stages, or in a tissue-restricted manner. The shared nature of TAAs across patients makes them attractive targets for off-the-shelf immunotherapies. However, no studies have comprehensively surveyed the TAA potential of all possible wild-type peptides originating from cancer-associated genes. In this study of 16 cancer tissue types and 39 normal tissue types, we analyzed the expression profiles of protein-coding genes to identify those with aberrantly high RNA levels across multiple solid tumor types and low RNA levels across all normal tissue types examined. We then developed a score to quantify tumor specificity of gene expression. Compared to previously reported TAA genes, those we identified exhibited substantially greater tumor specificity. Seven of these genes demonstrated consistently elevated expression in at least five tumor types and minimal expression across all non-immune-privileged normal tissues. To assess Human Leukocyte Antigen (HLA) class I presentation potential of the multi-cancer-associated genes, we computationally predicted the binding affinities between the most common class I HLA alleles and all possible wild-type TAA epitopes of 8–11 amino acids arising from those genes. We then applied rigorous filtering criteria to prioritize the most promising multi-cancer TAA peptide candidates and evaluated their HLA binding and cell-surface presentation using T2 and immunopeptidome analysis. Our results highlight new potential targets for multi-cancer immunotherapies.

Racial minorities remain underrepresented among allied health providers. Pathway programs address this gap by fostering career exposure and mentorship for underrepresented students. A pilot program was designed to increase underrepresented minority (URM) students entering health professions through career exploration and mentorship. High school students were enrolled into a pre-post survey study through a healthcare magnet school having higher proportions of economically disadvantaged students. Career exploration included healthcare presentations and skills sessions. Students were matched with mentors based on career interests. 22 students participated. The program facilitated career exploration sessions, mentor-mentee meetings, and workshops with diverse healthcare professionals. Participants reported increased likelihood towards pursuing healthcare careers. Preliminary findings suggest similar pilot pathway programs may increase URM student interest in healthcare careers.

Reasonable accommodations in higher education are being more frequently requested by graduate occupational and physical therapy students within didactic and clinical contexts. Researchers aimed to describe the experiences of clinical educators in occupational and physical therapy mentoring graduate students with a disclosed accommodation during terminal clinical education, employing a qualitative design. Semi-structured interviews and one-time electronic survey were completed. Reflexive thematic analysis was conducted following the approach described by Braun and Clarke. Twelve occupational or physical therapy clinical educators participated in semi-structured interviews, each having mentored 1–2 students with a disclosed disability accommodation during a terminal clinical education experience. Four major thematic categories regarding accommodation use in terminal clinical emerged: 1) accommodation process, 2) team approach to accommodating, 3) fostering accommodations, and 4) ambiguity in facilitating accommodations. Clinical educators emphasized the importance of being informed about accommodations well in advance, adapting teaching methods, and maintaining regular communication between academic institutions, clinical sites, and students. Training for clinical educators on the disclosure process, legal obligations, and strategies for effective mentorship to ensure alignment of accommodation, academic requirements, and site expectations is essential.

AIMS: Evidence-based medicine (EBM) is a necessary attribute required for quality medical practice. Despite being integral in advancing medicine and improving patient outcomes, research and quality improvement (QI) rarely integrate into medical education. We present our curricular course design and reveal students' perceptions of the implementation of this course. In addition, we compared physician assistant (PA) student perceptions from the first two traditional cohorts (4 years undergraduate before entry to PA program) to the accelerated 3+2 pathway cohorts (3 years pre-PA coursework followed by 2 years PA program). METHODS: Faculty developed an EBM course taught through student participation in QI projects and assessed students' perceptions of discovery, collaboration, cognitive ownership, and global sense toward general outcomes through the implementation and analysis of validated survey instruments. RESULTS: All students contributed to QI projects, achieved Quality Academy Bronze certification and Silver assessment and disseminated their work at peer-reviewed conferences. Over 56.4% earned Silver certification, and 36.2% of students had their project published in a journal. Student perception of experiential impact was positive overall, with 83.3% of students minimally responding 'true' to the prompts. All students indicated that after the experience, they possessed a basic understanding of QI approaches. The accelerated students selected 'true' for all other prompts more frequently than the traditional student population. DISCUSSION: This manuscript presents vital educational strategies, highlighting an approach and plan to extrapolate EBM principles beyond PA students and to generalize to other healthcare professionals and students. Through course completion, students met educational objectives and reaped additional benefits that positively impacted their resume building and future job prospects. By honing these skills, students are better prepared to contribute to patient care and advance the field of medicine. The accelerated students perceived greater course benefit likely due to the life-experience differences between the two cohorts, whereby the traditional students matriculated into the program with a breadth of prior knowledge obtained through years of contributions to education and careers.

The 2026 ASAHP (Association of Schools Advancing Health Professions) Clinical Education Committee recommendations present a framework for advancing clinical education across health professions. This report emphasizes the importance of expanding clinical education settings, integrating artificial intelligence and telehealth into curricula, ensuring alignment of interprofessional competencies with accreditation standards, and continuing to facilitate collaborative practice across disciplines. These efforts are essential to training a workforce that is not only clinically competent but also adaptable, mindful of equity, and capable of thriving in diverse, team-based care settings. Equally critical is the call to elevate research and scholarly activity within clinical education. The report emphasizes the need for academic-clinical partnerships that support and complete an inquiry into the value, effectiveness, and innovation of clinical training. These recommendations aim to advance a responsive, inclusive, and outcomes-driven clinical education system that benefits students, educators, healthcare systems, and the communities they serve. These efforts reflect ASAHP's name and mission to advance health professions.

Abstract Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p < 1 × 10 −5 ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.