Citations

Limited information on the business practices of liver transplant (LT) centers worldwide has been published. Characterizing this data could help identify best practices as well as opportunities for improvement. As such, the International Liver Transplant Society (ILTS) Business Practice Committee conducted a global online survey of LT centers, which was sent to the ILTS membership. Questions focused on 5 main domains: transplant practice and volumes, workforce, finances, quality assessment and performance improvement, and overall program function. Data was compared across program geographic regions and transplant volume. A total of 89 discrete centers were represented, of which 76.4% were academic/university-affiliated, and about one-third each were from Europe (36.0%) and North America (31.5%). The top 3 problems programs reported were finances/funding (60.7%), adequate program support/guidance (48.3%), and transplant volumes (43.8%). In all, 59.6% of respondents felt their salary was undercompensated, consistent across geographic regions. In addition, 69.7% felt their center was not adequately funded to meet program goals, with programs in Europe (N=28/32, 87.5%) and Oceania (N=2/3, 66.7%) most impacted. Transplant surgeon retainment was noted as more difficult for lower volume programs (<50 liver transplants/year, N=13/31). Nearly half (42.7%) of all programs felt under-resourced to provide high-quality care, and the majority (80.9%) felt there was room for growth and improvement under their current model. While international concerns varied widely among LT centers, inadequate salary and center funding, low transplant and referral volumes, and staff retainment were persistent themes. Focusing on adopting region-specific best practices and developing transplant systems of care that focus on these elements is critical to provide optimal care to LT patients worldwide.

PURPOSE Despite evidence of diagnostic accuracy but unclear long-term clinical benefit, national utilization patterns of prostate-specific membrane antigen positron emission tomography (PSMA-PET) are undefined. METHODS We conducted a serial cross-sectional study to evaluate the use of PET imaging among commercial insurance beneficiaries with prostate cancer using administrative claims from deidentified Blue Cross Blue Shield Axis database. Eligible patients included prevalent and incident prostate cancer cases. We calculated the proportions undergoing PET imaging in semiannual periods from January 1, 2016, through December 31, 2024. We examined the association between regional-level contextual sociodemographic and health care characteristics, and regional use of PSMA-PET imaging in 2024. RESULTS A total of 514,750 male beneficiaries age 40-89 years with prostate cancer were identified between 2016 and 2024. The proportion of individuals with prostate cancer undergoing PET imaging increased from 4.5 [95% CI, 4.1 to 4.9] per 1,000 in the first half of 2016 to 77.6 (95% CI, 76.2 to 79.1) per 1,000 in the second half of 2024, P < .001. Increases in PET were driven by uptake of PSMA-PET following approval in 2021, which increased from 0.8 (95% CI, 0.6 to 0.9) per 1,000 in the second half of 2021 to 77.0 (95% CI, 75.5 to 78.5) per 1,000 in the second half of 2024, P < .001. PSMA-PET use in 2024 was higher in regions with greater education (99.3 v 114.6 per 1,000 in lowest [Q1] v highest [Q4] educated) and income (95.4 v 112.3 per 1,000 in Q1 v Q4 income) measures, P < .001. CONCLUSION PSMA-PET was rapidly incorporated into clinical practice among commercial insurance beneficiaries with prostate cancer with higher adoption in geographic regions with higher income and education.

ABSTRACT Tumorigenesis and metastasis are frequently attributed to the intricate interplay between cancer cells and the tumor microenvironment (TME). Comprehending the mechanisms and key regulators of cancer‐immune crosstalk in the TME is imperative for developing efficacious immunotherapy. Through a series of in vivo CRISPR screens, we identified tumor‐intrinsic ITGB1 as a critical regulator of triple‐negative breast cancer (TNBC) development and deciphered its underlying mechanisms. Tumoral ITGB1 facilitated the establishment of pro‐tumorigenic TME by orchestrating tumor‐associated myeloid populations. Suppressing ITGB1 favored the enrichment of anti‐tumorigenic myeloid cells and enhanced infiltration of CD4 and CD8 T cells, culminating in superior antitumor effects. CRISPR scanning pinpointed a previously unrecognized functional domain essential for ITGB1's pro‐tumorigenic activity. This domain is distinct from all known ligand‐binding sites in ITGB1. An antibody capable of sterically blocking this domain significantly impaired TNBC progression. These findings position tumoral ITGB1 as a promising therapeutic target for reprogramming the TME from a pro‐ to an anti‐tumorigenic state, thereby effectively inhibiting TNBC development. Our study uncovers a novel mechanism of TNBC development and provides a unique therapeutic strategy for targeting ITGB1 in TNBC treatment.

Abstract High-grade gliomas (HGGs) are aggressive tumors with poor outcomes and limited treatment options. Here, we combined genomic and transcriptomic tumor profiling with drug testing in a patient-derived 3-dimensional culture model to identify individualized treatments and predictive biomarkers. Activity of single agents targeting frequently dysregulated glioma pathways was relatively poor ex vivo and generally reflected historical patient data. However, compounds targeting PI3K, epigenetic, and survival/senescence signaling were effective in some cases. Drug sensitivity correlated with transcriptional rather than genomic features and suggested heterogeneity as a resistance mechanism. Bromodomain and extraterminal domain inhibition was particularly effective in tumors enriched in the mesenchymal transcriptional subtype, promoted proneural transition, and was overcome by upregulated PI3K signaling. Notably, combinations were largely effective, with 6 strategies exhibiting stronger efficacy than corresponding single agents in most cases (58-77%). This study identifies HGG vulnerabilities and associated biomarkers, resistance mechanisms, and effective combination strategies that warrant further clinical validation. Graphical Abstract

Introduction: Underrepresented in family medicine (URiFM) physicians hold 14.42% of US family medicine faculty positions. Scholarship is critical to academic advancement. We explored family medicine department chairs’ racial allyship, their identification of scholarship barriers faced by URiFM faculty, and the existence of initiatives to increase scholarship. Methods: We used the 2022 Council of Academic Family Medicine Educational Research Alliance (CERA) Department Chair survey to examine the percentage of chair-perceived URiFM departmental faculty members and their scholarly productivity and chair-perceived barriers to productivity and initiatives. We measured chairs’ racial allyship. We calculated descriptive statistics, weighted means, and used regression to identify whether chair characteristics or allyship scores were associated with support of URiFM faculty scholarship initiatives and identification of the minority tax. Results: One hundred nine chairs completed the survey (response rate 48.4%); 13.76% identified as URiFM; 6.4% reported they perceived more than 50% of their faculty were URiFM; 90.8% of chairs did not report programs supporting URiFM scholarship; and 44.9% described URiFM faculty scholarly output as minimal or none. Department chairs’ mean allyship score was 2.59 (SD = 0.80) out of 5. Chairs ranked lack of research skills and lack of funding for protected time higher than the minority tax from a list of scholarship barriers. We found no association between chair allyship scores, chair characteristics, total department full-time equivalents, and the existence of a URiFM faculty scholarly support program. Discussion: Despite chairs reporting low URiFM faculty scholarly output, few departments have a dedicated support program. Chair allyship scores were not associated with identification of scholarship barriers or existence of scholarship programs.

Abstract Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for weight management. Although generally well-tolerated, these agents may alter the pharmacokinetics of concurrently administered medications. Case Presentation A 23-year-old male with schizoaffective disorder, bipolar type, developed lithium toxicity shortly after switching from semaglutide to tirzepatide. While taking semaglutide, the patient was started on lithium and titrated to 1800 mg nightly, corresponding to a level of 0.9 mEq/L. Four days after his first dose of tirzepatide, he reported early symptoms of potential lithium toxicity, which progressed significantly after the second dose. Symptoms corresponded to a 15-hour post-dose level of 1.7 mEq/L, despite no changes in renal function, hydration status, or other concurrent medications. Management with intravenous fluids was sufficient, and lithium dose reduction prevented future toxicity. Discussion Application of the Drug Interaction Probability Scale suggests a probable interaction between tirzepatide and lithium. The interaction might be mediated through delayed gastric emptying or other pharmacokinetic changes. Limited reports of GLP-1-modulating agents associated with lithium toxicity have been published and may be an underrecognized phenomenon. To date, no pharmacokinetic studies have been published evaluating this potential drug-drug interaction. Although many other medications seem to be at risk for decreased absorption, tirzepatide may enhance the absorption of lithium. Conclusion Clinicians should be vigilant when initiating or switching GLP-1-modulating agents in patients receiving lithium. Pharmacokinetic studies are needed to clarify the mechanism of this interaction. Until more is known, increased monitoring of lithium levels is warranted, with initiation of a GLP-1-modulating agent, a dose change, or switching to another agent.