Citations

Importance The definition of cure in stage II to III colon cancer (CC) remains unclear due to limitations in conventional end points, which include deaths and second primary tumors as events. These can complicate communication with patients regarding long-term outcomes. Objective To distinguish relapses from competing health-related events to classify long-term outcomes years after surgery and explore when the incidence of true relapses of the initial CC approaches 0% to define cure in this disease. Design, Setting, and Participants This pooled analysis of individual patient–level data from 15 phase 3 randomized clinical trials assessed time to CC-related relapse using Kaplan-Meier and Aalen-Johansen methods, with death and second primary tumors treated as competing risks. Cox regression models evaluated prognostic associations, stratified by sex, stage, and tumor. Patients with stage II to III CC who underwent adjuvant chemotherapy were included. All patients had undergone radical surgery for CC and received adjuvant chemotherapy with a median follow-up of at least 6 years. The Adjuvant Colon Cancer Endpoints (ACCENT) and the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) databases included adjuvant studies conducted between 1996 and 2015. Data were analyzed from February 2022 to June 2025. Exposures Adjuvant chemotherapy regimens varied across trials, including fluoropyrimidines alone or in combination with oxaliplatin or biologic agents. Main Outcomes and Measures The primary outcome was time to CC-related recurrence. The predefined threshold for cure was a recurrence risk below 0.5%. Results Of 35 213 included patients, 19 346 (54.9%) were male, and the mean (SD) age was 60.2 (10.8) years. The incidence rate of recurrence peaked at 6.4% (1993 of 31 373) between month 6 and month 12 and decreased continuously until year 10 of follow-up never exceeding 0.5%. Recurrence rate appeared to increase again after year 10 and peaked at 2.0% during year 12.5 to year 13, a pattern observed exclusively in the MOSAIC trial. Competing-event analysis revealed that death and second primary tumors inflated the apparent recurrence rate, especially for older patients. The overall cumulative incidence of relapse with death as competing risk was lower among female patients (hazard ratio, 0.58; 95% CI, 0.45-0.76; P < .001). Conclusions and Relevance In this pooled analysis of phase 3 randomized clinical trials, a recurrence rate less than 0.5% occurred after 6 years from surgery, supporting a practical definition of cure. Recognizing this milestone may improve patient communication, guide follow-up duration, and reduce unnecessary long-term surveillance.

Abstract Medical imaging is undergoing a transformation driven by the advent of new, highly effective, machine learning techniques paired with increases in computational capabilities (Cheng et al. 2021; Gilson et al. 2023; Almeida et al. 2024; Krishna et al. 2024). These advanced algorithms have the potential to improve disease detection, diagnosis, prognosis, and treatment outcomes. However, the complexity of machine learning models, the large amounts of curated and annotated data required by some methods, and the potential for bias and error make it challenging for individuals to safely and effectively leverage these methods (Lin et al. 2024; Guo et al. 2024; Xu et al. 2024; Linguraru et al. 2024; Wood et al. 2019). To address these challenges, the American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), Radiological Society of North America (RSNA), and Society for Imaging Informatics in Medicine (SIIM) have worked together to develop a syllabus detailing a recommended set of competencies for medical imaging professionals interacting with these systems. This guide is aimed at four different personas: users of AI systems, purchasers of AI systems, individuals who provide clinical expertise during the development of AI systems (“clinical collaborators”), and developers of AI systems.1 This is a syllabus, not a curriculum, and is intentional in this scope. Recognizing that individuals may benefit from different presentations of the same material, this work enumerates a series of relevant competencies but does not prescribe, nor offer, a method of instruction (Schuur, Rezazade Mehrizi, and Ranschaert 2021; Garin et al. 2023). By addressing the task‐specific demands of each role, this guide will enable medical imaging professionals to utilize machine learning systems more safely and effectively, ultimately improving patient care and outcomes.

Ischemic cardiomyopathy (ICM) is a leading cause of heart failure characterized by extensive remodeling of the cardiac extracellular matrix (ECM). While initially adaptive, ECM deposition following ischemic injury eventually turns maladaptive, promoting adverse cardiac remodeling. The strong link between the extent of fibrosis and adverse clinical outcomes has led to growing interest in ECM-targeted therapies to prevent or reverse maladaptive cardiac remodeling in ICM; yet, the precise composition of the ECM in ICM remains poorly defined. In this study, we employed sequential protein extraction enabled by the photocleavable surfactant Azo to enrich ECM proteins from left ventricular tissues of patients with end-stage ICM and nonfailing donor hearts. High-resolution mass spectrometry–based quantitative proteomics identified and quantified over 6,000 unique protein groups, including 315 ECM proteins. We discovered significant upregulation of key ECM components, particularly glycoproteins, proteoglycans, collagens, and ECM regulators. Notably, LOXL1 , FBLN1 , and VCAN were among the most differentially expressed. Functional enrichment analyses revealed enhanced TGFB signaling, integrin-mediated adhesion, and complement activation in ICM tissues, suggesting a feedback loop driving continued ECM deposition in the end-stage failing heart. Together, our findings provide a comprehensive proteomic landscape of ECM alterations in the end-stage ICM myocardium and identify promising molecular targets for therapeutic intervention.

Abstract Pancreatic adenocarcinoma (PDA) has poor response to chemotherapy with a strong likelihood of cancer recurrence. While previous studies have examined patient samples collected before and after chemotherapy, few have analyzed matched samples from the same patients that allow us to deconvolute interpatient heterogeneity, a large limitation to PDA studies. Here, we study the effects of chemotherapy on tumor cells and their surrounding microenvironment using scRNA sequencing of matched pre- and post- treatment tissue biopsies from 5 patients. We utilized the Seurat v4 pipeline to observe transcriptomic differences and corresponding putative cellular interactions in both treatment states. Unsurprisingly, we found insufficient tumor epithelial cells post-treatment due to the intended cytotoxic effects of chemotherapy, leading us to focus on the tumor microenvironment where we had sufficient cells to analyze. We identified that immune cells in the TME are heterogeneously affected by chemotherapy treatment with patient specific differences, but we did identify a unanimous increase in CXCR4 in CD4 and CD8 positive T cells after treatment. Analysis of CAFs revealed that a subset of fibroblasts lose myofibroblastic features and increasingly acquire 'neural'-like features after treatment. This suggests that chemotherapy-altered fibroblasts may contribute to a pro-tumor microenvironment that facilitates recurrence through neuron–CAF–tumor interactions. Through inferred ligand-receptor pairs identified with the CellChat v2 pipeline, we observed that increased CXCL12 in these neural CAFs interacts with the increased CXCR4 on T-cells. We validated the expression of these genes in patients by staining human patient PDAC tissues (both treated and treatment naïve tissues) for neural genes that were highly enriched post-treatment in our single cell sequencing dataset. We have also begun inhibiting these genes of interest in CAFs and are exploring the effects of these ‘neural’-CAFs on patient-derived tumor organoids in culture. Citation Format: Aylin Z. Henstridge, Padma Kadiyala, Ahmed Elhoissiny, Jianhua Liu, Georgina Branch, Nandini Arya, Vaibhav Sahai, Nicole Peterson, Jorge Machicado, Richard Kwon, Allison Schulman, Erik Wamsteker, George Phillips, Martin Fernandez-Zapico, Mark Truty, Timothy Frankel, Fillip Bednar, Marina Pasca di Magliano, Costas Lyssiotis, Eileen S. Carpenter. An increase in neural cancer associated fibroblasts following exposure to chemotherapy in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B079.

Objectives: There is a paucity of research comparing the outcomes of medial ulnar collateral ligament (MUCL) repair with internal bracing to isolated MUCL reconstruction in professional baseball players. Further, the practice of supplementing a MUCL reconstruction with an internal brace, a "hybrid" reconstruction, has increased in the surgical treatment of MUCL injuries for professional baseball players, without any currently known published research defining the clinical outcomes of this modification. We sought to investigate the trends and outcomes of MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing. Using a matched cohort analysis, we also sought to compare the clinical outcomes of both MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing to isolated MUCL reconstructions, without internal bracing, in professional baseball players. Methods: The MLB Health and Injury Tracking System was used to identify all professional baseball players who underwent MUCL surgery, regardless of surgery technique, from 2010 to 2023. Professional players of all levels (MLB and MiLB) and players of all positions were included. Player demographics, injury characteristics, surgical details, and postoperative outcomes were obtained. Player demographics included age at surgery, position of play, professional level of play and surgical technique. Outcomes assessed were return to play (RTP) status, time to RTP, return to same level of play (RTSL), time to RTSL, revision MUCL surgery, and time to revision MUCL surgery, with a minimum of 2 years of follow up. Players were considered to have RTP if they participated in at least one game at any professional level. RTSL was defined as returning to the same league of professional play or higher. Patients undergoing MUCL repair and "hybrid" MUCL reconstruction with internal bracing were independently compared to propensity matched patients undergoing isolated MUCL reconstruction, without internal bracing, to assess for a difference in postoperative outcomes. Four subgroup analyses were conducted by further categorizing patients to MLB players, MiLB players, pitchers, and position players. Results: 76 patients underwent MUCL repair with internal bracing from 2016-2021 and were successfully propensity matched to 76 patients undergoing isolated MUCL reconstructions. Baseline patient demographic variables of MUCL repairs were statistically similar to those of controls except for age at time of surgery (24.5 vs 21.8; p<0.001). 81 patients underwent "hybrid" MUCL reconstructions with internal bracing from 2016-2021 and were successfully propensity matched to 81 patients undergoing isolated MUCL reconstructions. Baseline demographic variables of "hybrid" MUCL reconstructions were statistically similar to those of controls except for age at time of surgery (24.3 vs. 23.3; p=0.006). Compared to isolated MUCL reconstruction controls, all patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.2 vs. 546.2 days; p<0.001), shorter time to RTSL (mean 436.2 vs. 558.8 days; p<0.001), and shorter time to revision (mean 465.2 vs.1648 days; p=0.036). The number of patients who RTP at any level, RTSL, and number of revision surgeries were not significantly different. Compared to isolated MUCL reconstruction controls, all patients undergoing "hybrid" MUCL reconstructions demonstrated no significant differences with respect to the number of patients who RTP, time to RTP, number of patients who RTSL, days to RTSL, number of revision surgeries, and time to revision surgery. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 282.8 vs 507.3 days; p=0.008) and shorter time to RTSL (mean 299.7 vs. 598.0 days; p = 0.024). No other outcomes were significant. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 436.2 vs. 525.3 days; p=0.026). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 444.3 vs 550.7 days; p<0.001) and shorter time to RTSL (mean 451.7 vs. 556.5 days; p<0.001). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated no significant differences in outcomes. In evaluating pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.7 vs. 578.6 days; p<0.001), shorter time to RTSL (mean 434.8 vs. 591.6 days; p <0.001), and shorter time to revision surgery (mean 465.2 vs.1648 days; p=0.036). No other outcomes were significant. In pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 488.1 vs. 549.0 days; p=0.013) and shorter time to RTSL (mean 505.7 days vs. 577.0 days, respectively; p=0.021). No other outcomes were significant. Notably, all revision surgeries in occurred in pitchers only. Conclusions: Based on a matched cohort anaylsis of professional baseball players undergoing MUCL surgery, when compared to an isolated MUCL reconstruction, MUCL repair with internal bracing may allow for a shorter time to RTP and RTSL, with a shorter time to revision surgery. For pitchers, "hybrid" MUCL reconstruction may allow for a shorter time to RTP and RTSL. For MLB players, "hybrid" MUCL reconstruction may allow for a shorter RTP.

Objectives: The number of medial ulnar collateral ligament (MUCL) reconstructions are increasing. The epidemiology surrounding revision MUCL reconstructions in professional baseball players has not been well defined. The purpose of this study was to report the epidemiology of revision MUCL reconstruction in professional baseball players. The authors hypothesized that the number of revision MUCL reconstructions would increase over time and that the return to sport rate at the same level of play would be less than 70%. Methods: All professional baseball pitchers who underwent revision MUCL reconstruction between 2010-2023 were identified using the MLB Health and Injury Tracking System (HITS). Rate of return and time to return to play (RTP) and return to same level of play (RTSL) was recorded and analyzed for pitchers with a minimum follow up of 2 years. Surgical variables including technique and graft choice were also recorded. Results: Overall, 191 pitchers (avg age 26.0 years), underwent revision MUCL reconstruction. The average time between primary and revision surgery was 1,381 days (45 months). 130 (68%) of these players were MLB pitchers and the other 61 (32%) were MiLB pitchers. 59% of pitchers were able to RTSL at an average of 604 ± 250 days after surgery. 2023 was the year with most revision MUCL reconstructions (n = 27) and the fewest reconstructions were performed in 2010 and 2011 (n = 4). Monthly distribution demonstrates the highest surgery months to be May (17%), June (20%), and July (17%). Hamstring tendon autograft was found to be the most commonly used graft source (n = 90, 47%), compared to palmaris longus autograft (n = 67, 35%). No significant differences were found in the types of grafts used over time ( P = .238 for palmaris and P = .133 for hamstring). In terms of tunnel configuration, both the Modified Jobe and Docking techniques were used in equal occurrence (n = 70, 37%) Conclusions: Following revision MUCL reconstruction, only 72% of professional baseball pitchers were able to return to play at any level at an average of 556 days (18 months), and only 59% were able to return to the same level of play at an average of 604 days (20 months). The average time between primary and revision MUCL reconstruction was 45 months (3.75 years). Pitchers should be counseled on the relatively low RTSL rate and the prolonged time to RTSL.