Citations

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.

Objectives: There are few studies that have closely evaluated the outcomes of ulnar collateral ligament repair and reconstruction (UCLR) in position players (PP). The objective of this study was to determine the outcome of UCLR in professional baseball players who play in non-pitcher positions, i.e. PP. Methods: The approval of the Major League Baseball (MLB) Research Committee was obtained. All PP who underwent surgery for their UCL while active on an MLB or Minor League Baseball (MiLB) team were identified using The MLB Health and Injury Tracking System. PP who underwent UCLR from 2010 to 2023 were analyzes, however for data that concerned PP time to return to professional play, only players who underwent UCL surgery from 2010 to 2021 were evaluated in order to ensure the presence of a minimum of 2-year follow-up data. Return to play (RTP) was defined as a player who played in at least 1 game at any professional level (A, AA, AAA, or MLB). Players were deemed to return to the same level of play (RTSLP) if they played in at least 1 game at the same competition level or higher that they played in prior to their UCL surgery. PP who had a time to RTP or a time to RTSLP that exceeded 800 days were excluded from any analysis that concerned the time to return to play. PPs were also compared to a cohort of professional baseball pitchers who had also undergone UCL surgery. Results: From 2010 to 2023, 241 PP underwent surgery for their UCL at a mean age of 23.4 ± 4.3 years old (Table 1). Overall, PP had their UCL surgery at approximately a mean of 3.7 ± 3.3 years after the start of their professional career (Table 1). Further, apart from the year 2020, the annual number of UCL surgeries performed in MLB and MiLB PP demonstrated an upward trend from 2010 to 2023, although no trends in the distribution of UCL surgeries across position type or between major and minor players exist. No statistically significant differences in RTP nor RTSLP rates following UCL surgery in PP existed when comparing across position type (catcher vs. infielder vs. outfielder) and across surgery type (repair vs. reconstruction vs. reconstruction with augmentation) (Table 2). PP who underwent repairs were able to RTP at a median of 221 days (IQR: 81), which was sooner than PP who underwent reconstruction surgery (median: 383 days, IQR: 316) or reconstructions with augmentation (median: 456 days, IQR: 219) (P = 0.002) (Table 3). PP with UCL repairs were also able to RTSLP sooner (median: 234 days, IQR: 64) than PP who underwent reconstructions (median: 394 days, IQR: 305) or reconstructions with augmentation (median: 462 days, IQR: 242) ( P = 0.003) (Table 3). Further, infielders RTP sooner (median: 335 days, IQR: 157) than catchers (median: 396 days, IQR: 283) and outfielders (median: 412 days, IQR: 366) ( P = 0.036) (Table 3). Similarly, infielders RTSLP sooner (median: 334 days, IQR: 162) than catchers (median: 470 days, IQR: 281) and outfielders (median: 426 days, IQR: 354) ( P = 0.016) (Table 3). Following UCL surgery, PP were able to RTSLP, on average, more than 2 months sooner than pitchers (429 ± 177 days for PP vs 499 ± 153 days for pitchers, P < 0.001). PP who underwent repair of their UCL were able to RTSLP over 4.5 months, on average, sooner than pitchers who underwent UCL repair (269 ± 125 days for PPs vs 405 ± 153 days for pitchers, P < 0.001) and PP who underwent reconstruction of their UCL were able to RTSLP just under 50 days sooner than pitchers who had their UCLs reconstructed (450 ± 175 days for PPs vs 498 ± 151 days for pitchers, P < 0.001) (Figure 1). Conclusions: Few studies have examined PP outcome data following UCLR surgery. As such, there is little understanding as to the differences in return to game rates between various baseball non-pitcher positions as well as the differences in the time it takes to RTP and RTSLP. This study highlights that the annual number of UCLR surgeries demonstrates an upward trend. This retrospective analysis also highlights that PP with UCL repairs were able to RTP and RTSLP sooner than PP who underwent UCL reconstructions and UCL reconstructions with augmentation. Furthermore, infielders were able to RTP and RTSLP sooner than catchers as well as outfielders. The results of this study demonstrate that the type of UCL surgery as well as the player’s position does not seem to significantly impact whether or not a player actually returns to playing professional baseball, however it does impact the speed at whichthey are able to return (provided they do return to playing baseball). As such, the results of this study may be used to counsel PP regarding speed at which a return to playing baseball can be expected.

Objectives: The medial ulnar collateral ligament (MUCL) is the primary stabilizer of valgus forces across the elbow. Injury to the MUCL has a large impact on the throwing athlete, particularly in baseball. The incidence of MUCL injury in baseball pitchers is on the rise. Surgical treatment and rehabilitation is evolving to improve outcomes and improve return to sport time frames. The purpose of this study was to highlight the trends in MUCL repair and reconstruction in professional baseball pitchers, describe relevant outcomes such as return to any level of play (RTP) for surgical repair and reconstruction, and distinguish what factors might impact these outcomes. The authors hypothesize that primary and revision MUCL surgery is increasing with revision surgery requiring the greatest time to RTP. Methods: The Major League Baseball (MLB) Health and Injury Tracking System (MLB HITS) database was used to procure data during the targeted study period (2010 – 2023). All professional pitchers who underwent MUCL surgery within the study period were included. Variables analyzed included age, career length, and level of play. Surgical variables included date and type of procedure, RTP status, time required to RTP, return to same level of play (RTSL), career length before and after surgery, number of revision surgeries, and time between surgeries. Successful RTP was designated if a pitcher had returned in at least one professional game after index surgery. Analyses of trends over time were performed. The year 2020 was considered an outlier and omitted from the analysis of trends due to the coronavirus pandemic which limited games played. Results: A total of 2,287 pitchers underwent MUCL surgery during the study period (Table 1). The annual number of MUCL surgeries on all pitchers increased year over year (R 2 = 0.821, p < 0.001), as did the annual number of reconstructions with internal brace (IB) augmentation (R 2 = 0.896, p < 0.001) (Figure 1). The RTP rate (93%) for MLB pitchers was significantly higher compared to the RTSL rate (71%, P < 0.001). This difference was not observed in Minor League Baseball (MiLB) (RTP 76% vs. RTSL 74%, P = 0.142) (Figure 2). The percentage of players who RTP after revision surgery was significantly lower compared to primary surgery (71%vs. 80% respectively, P = 0.020). Mean time to RTP is significantly shorter (470 ± 135 days) compared to the mean time to RTSL (499 ± 153 days, P < 0.001) (Figure 3). The annual number of revision MUCL surgeries on all pitchers increased year over year as well (R 2 = 0.322, p = 0.043). Conclusions: MUCL surgery continues to increase, also leading to increasing numbers of revisions in professional pitchers. Overall, 80% of pitchers were able to RTP at a mean of 470 days (15.5 months), while only 71% were able to RTSL at a mean of 499 days (16.5 months), but this varied based on level of play. Surgical techniques continue to evolve as MUCL repairs and reconstructions with IB augmentation have increased significantly in recent years. This study will help guide athlete expectations and surgeon decision-making.