Faculty Bibliography

In the face of a growing mismatch between candidates awaiting transplantation and the supply of conventional donor organs, attention has shifted toward novel methods to increase the donor pool, including the use of donation after circulatory death (DCD) and the refinement of procurement techniques that safeguard graft quality. Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a new strategy, leveraging extracorporeal support to curtail warm-ischemic injury while permitting in situ functional assessment. This review covers the rationale behind the use of TA-NRP, while outlining its use during procurement and the current body of evidence gathered on it implementation in lung transplantation specifically.

Protease-activated receptor 2 (PAR₂) mediates oral cancer pain. Patients with metastatic (N + ) cancers report greater pain. PAR₂ is activated by N-terminal proteolytic cleavage. Here we show that proteases encoded by genes overexpressed in N+ cancers from patients with pain (matrix metallopeptidase 1, MMP1 and serine protease 23, PRSS23) elicit protease-specific receptor redistribution (trafficking) and signaling that differs from that promoted by proteases encoded by genes not differentially expressed (transmembrane serine protease matriptase, ST14 and cathepsin S, CTSS). Mixtures of the proteases prepared to model the oral cancer microenvironment revealed that ST14-mediated PAR₂ activation predominated at low protease concentrations. At high concentrations, MMP1 and PRSS23 prevailed over the greater potency of ST14. We propose that PAR₂ activation in oral N+ cancers from patients with pain is driven by high levels of MMP1 and PRSS23. Our study informs design of signaling and location-specific antagonists to provide more efficacious analgesia.

School-based health centers (SBHCs) play a key role in connecting youth to health services, including primary care. Despite some literature exploring their mental health services, little is known about the role SBHCs play in screening for and treating eating disorders. In this study, we surveyed 56 SBHC providers, assessing their familiarity with providing care and screening for mental health concerns, including eating disorders. We also qualitatively explored areas to improve efforts around mental health care and screening. Results suggest that while the majority of participants indicated that they were familiar with mental health disorders, they were less familiar with eating disorders. Furthermore, despite rating screenings for eating disorders of great importance, the frequency of such screenings was comparably lower. Qualitative findings highlight two emerging themes focused on addressing gaps in mental health care: (a) training, continuing education, and addressing misconceptions around eating disorders; and (b) SBHC staffing and resource constraints.

Background MR enterography (MRE) is increasingly used to guide treatment and improve outcomes in Crohn disease (CD). An abbreviated MRE (A-MRE) protocol-omitting contrast and antiperistaltic agents-may reduce scanning time and cost and improve compliance. Purpose To compare intrareader concordance and interreader agreement in detecting disease activity and disease-related complications using contrast-enhanced MRE (CE-MRE) versus an A-MRE protocol in participants with CD. Materials and Methods In this secondary analysis of a prospective study, 10 abdominal radiologists independently reviewed MRE examinations from a prospective study of participants with CD before and after treatment with biologics, using both A-MRE and CE-MRE protocols, at least 1 month apart. Interreader agreement and intrareader concordance were assessed using Gwet first agreement coefficient (AC1) at both the segment and participant levels for the presence of active inflammation, associated indicative features, and complications. Diagnostic accuracy of the simplified MR index of activity (sMaRIA) was evaluated against ileocolonoscopy when available. Results This study included 60 participants (median age, 36 years [IQR, 28-44 years]; 40 female; 80 examinations). Interreader agreement for detecting intestinal active disease was high and comparable between A-MRE and CE-MRE at the participant level (AC1, 0.87 [95% CI: 0.79, 0.95] vs 0.91 [95% CI: 0.85, 0.97]). For strictures, similar interreader agreement was observed between protocols (AC1: A-MRE, 0.61 [95% CI: 0.47, 0.74] vs CE-MRE, 0.50 [95% CI: 0.35, 0.65]). For penetrating complications, the interreader agreement was also similar between protocols (A-MRE, 0.71 [95% CI: 0.56, 0.86] vs CE-MRE, 0.76 [95% CI: 0.63, 0.90]). The intrareader concordance between protocols for detecting active inflammation and CD complications was almost perfect for all readers (AC1 range, 0.86-1.00). In the terminal ileum, sMaRIA showed high sensitivity (A-MRE, 96.4%; CE-MRE, 98.4%) and specificity (A-MRE, 68.1%; CE-MRE, 71.4%) for detecting inflammation. Conclusion An A-MRE protocol demonstrated comparable interreader agreement to conventional CE-MRE and high intrareader concordance for detecting active CD and related complications in participants with CD. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Ohliger in this issue.

Oncofertility is the practice of joining oncology clinicians with reproductive endocrinologists to assess patients' tumor biology, tumor stage, and mutation analysis to discuss the infertility risks from tumor-directed treatments and provide fertility preservation opportunities to patients who will undergo or have received tumor-directed therapy since cancer treatments can affect fertility. Tumor-directed therapies, such as radiation and antineoplastic agents, have greatly expanded beyond traditional deoxyribonucleic acid (DNA)-damaging agents to encompass pharmacologic agents, such as targeted monoclonal antibodies, kinase inhibitors, and immune activating therapies that may have varying effects on women's fertility. Here, we review the current literature to provide a comprehensive summary on the effect of cancer treatment modalities on female fertility, fertility preservation options in female patients, and the role of pharmacists in oncofertility practice.

Dpep is a cell-penetrating peptide that targets transcription factors ATF5, CEBPB and CEBPD to selectively suppress growth and survival of diverse tumor cell types in vitro and in vivo. Due to these actions and its apparent safety, the peptide has potential as a cancer therapeutic. How Dpep might be combined with other anti-cancer agents to achieve synergistic efficacy and to overcome possible peptide resistance has not been assessed in depth. Based on prior work indicating that Dpep promotes apoptotic cancer cell death and up-regulates multiple pro-apoptotic and tumor suppressor genes, we studied combinations of Dpep with ABT-263, a pro-apoptotic BCL2 family inhibitor, and decitabine, a hypomethylating drug. Combining Dpep with each agent alone or together synergistically suppressed the growth of a range of solid and liquid tumor cell types. Moreover, the combinations synergistically inhibited the growth of cells lines that were selected either in vivo or in vitro for Dpep resistance. Finally, we tested the combination of Dpep with ABT-263 in a mouse melanoma xenograft model. The combination more effectively inhibited tumor growth than either agent alone and, in contrast to vehicle or ABT-263, produced a 40% durable survival rate. Taken together, these observations highlight potential drug partners for the therapeutic development of Dpep.

BACKGROUND:Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, accounting for more than 900,000 deaths a year worldwide. Microbial dysbiosis, including the presence of oral bacteria in the gut, has been linked to CRC. Some mechanisms by which specific microorganisms potentially drive tumorigenesis have been described, but there is a lack of studies elucidating whole microbiota activity in the tumor and their implication for the development of the disease. Here, the metatranscriptomic data of tumor and control tissue-associated microbiota (n = 18 pairs), as well as from subgingival sulcus (n = 15) of CRC patients, was analyzed. RESULTS:We confirmed that Fusobacterium nucleatum was more active in the tumor tissue than in the control gut mucosa. In addition, the activity of this species was positively correlated with other oral bacteria in the tumors, including Parvimonas micra, Peptostreptococcus stomatis, and Granulicatella adiacens, along with gut bacteria like Hungatella hathewayi, suggesting a potential relationship among them. Regarding bacterial gene expression, a change in the functional profile was observed, including a higher expression of genes associated with carbon metabolism in control in contrast to an increase of amino acid-related genes in tumor. Furthermore, genes implicated in the biosynthesis and transport of lipopolysaccharide were increased in tumors. Interestingly, a significantly higher expression in tumor than control tissue of potential virulence factors from F. nucleatum was found, supporting their relevance in niche colonization and tumorigenesis. Correlation analysis of the bacterial activity with the host transcriptional profile showed significant correlations of the Fusobacterium-Peptostreptotoccus-Hungatella cluster with human genes involved in inflammation and metastasis, confirming the association of this microbial consortium with tumor development. For the first time, the gene expression profiles of oral bacteria in the gut and the oral cavity were compared. The cluster of co-active bacteria identified in tumors was partially found in the oral samples, suggesting a stable interaction and potential synergy. Although there were thousands of differentially expressed genes between subgingival sulcus and tumor tissue, the expression of key virulence factors was not significantly different. CONCLUSIONS:In short, this study discovered new traits about tumor microbial-associated composition and activity and its connection with the oral composition that would be essential to unravel the translocation, colonization, and tumorigenesis of the CRC.

STUDY DESIGN/METHODS:Prospective multicenter study. OBJECTIVE:To determine the incidence of all-cause mortality after adult spinal deformity surgery. SUMMARY OF BACKGROUND DATA/BACKGROUND:Patients undergoing adult spinal deformity surgery are often frail and the procedures are invasive. The incidence of all-cause mortality among patients undergoing cervical or thoracolumbar deformity surgery is unclear. METHODS:Using 2 prospective, multicenter databases, we identified patients who underwent surgery for cervical deformity surgery from 2013-2020 (n=169) or thoracolumbar deformity from 2008-2020 (n=1507). Mortality incidence density was calculated as follows: 100 × (number of deaths) / (sum of total years of follow-up for all patients). RESULTS:Of 169 participants in the cervical group (mean±standard deviation age, 61±10 y), death occurred in 19 (11%). The mean time to death was 25±19 months. Mortality incidence density was 4.4 deaths per 100 person-years. The 30-day mortality rate was 0.6% (1/169) and 90-day mortality rate was 1.2% (2/169). The 3 most common causes of death were arrhythmia/cardiac arrest (16%), congestive heart failure (11%), and pneumonia (11%). There were no intraoperative deaths. Of 1507 participants in the thoracolumbar group (mean±standard deviation age, 61±14 y), death occurred in 53 (3.5%). The mean time to death was 32.5±21.5 months. Mean duration of follow-up was 1.8±1.5 years. The mortality incidence density was 0.8 deaths per 100 person-years. The 30-day mortality rate was 0.1% (1/1507) and 90-day mortality rate was 0.3% (4/1507). The 3 most common causes of death were non-spine malignancy (13%), pneumonia (9%), and arrhythmia/cardiac arrest (6%). CONCLUSIONS:The number of deaths per year was higher among cervical deformity patients (4.4 per 100 person-years) than among thoracolumbar deformity patients (0.8 per 100 person-years). Pneumonia and arrhythmia/cardiac arrest were among the most common causes of death in both groups. LEVEL OF EVIDENCE/METHODS:III.

Post-traumatic stress disorder (PTSD) is a maladaptive and debilitating psychiatric disorder that develops after exposure to a severe traumatic event. PTSD is characterized by intrusive re-experiencing of traumatic memories, avoidance of trauma reminders, negative alterations in cognition and mood, and changes in arousal and reactivity. PTSD is prevalent, with tens of millions of patients in the USA alone affected. The lifetime prevalence worldwide is estimated to be about 4-6%, but it can occur in up to 25-30% of people who experience severe psychological trauma, such as combat veterans, refugees and assault victims. PTSD is highly comorbid with major depressive disorder, anxiety disorders and substance use disorders, and it is a leading cause of suicide. PTSD also increases the risk of multiple medical problems including cardiovascular and metabolic disorders. We review the epidemiology and diagnostic aspects of PTSD in adults, the mechanistic and neurobiological understanding of the syndrome - from neural circuitry to genetic mechanisms - as well as medication, psychotherapy and other trauma-informed treatment approaches to PTSD and trauma-related syndromes.