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Background While rapid response teams (RRT) are widely implemented to address clinical deterioration in hospitalized patients, their impact on goals of care (GOC) discussions remains underexplored. Aims We aimed to evaluate whether RRT activations were associated with subsequent goals of care discussions, code status changes, and clinical outcomes. Methods We conducted a retrospective single-center review of hospitalized adult patients admitted to medicine services who had RRT activations between January and December 2023. The primary outcome was GOC discussion within 72 h of RRT. GOC discussions were identified through EMR documentation of conversations, code status changes, and ACP notes. Secondary outcomes included code status change, transition to comfort care, and 30- and 90-day mortality. Analyses were adjusted using inverse probability of treatment weighting. Results 1823 RRTs among 1677 patients were analyzed; 47% of patients were female and 88% identified as white. Those transferred to the ICU had higher odds of goals of care discussions (OR 1.52, P < 0.001), code status change (OR 2.43, P < 0.001), and transition to comfort care (OR 1.47, P = 0.026) compared to those who remained on the floor. ICU transfer was also associated with increased 30- (OR 1.39, P = 0.006) and 90-day mortality (OR 1.30, P = 0.014). Conclusions ICU transfer following RRT activation is strongly associated with downstream goals of care discussions, changes in code status, comfort-focused care, and higher mortality. This demonstrates the importance of initiating goals of care discussions early and often, regardless of whether clinical decompensation is anticipated.

Previous studies about the COVID-19 pandemic on STEMI patient outcomes have conflicting results. It remains unclear if this may be attributed to regional differences and/or differences during COVID-19 wave periods. Using the American Heart Association Get With The Guidelines–Coronary Artery Disease registry data, we evaluated (1) time metrics related to STEMI system goals and (2) regional variation in STEMI incidence and in-hospital mortality during pandemic wave time periods. The study included all patients 18–100 years old admitted with STEMI (n = 72,516) to 1 of 435 American Heart Association Get With The Guidelines–Coronary Artery Disease hospitals (1 October 2019–31 December 2021). Of these, 70.8% were male and 73.0% non-Hispanic White, with a median age of 63 (IQR 18) years. Compared to pre-pandemic time frames, patients with STEMI had a higher risk profile, delayed time to treatment, were treated with fibrinolytic therapy or primary PCI, and were transferred for primary PCI at similar rates, and had higher adjusted in-hospital mortality (during the second wave in the South and Midwest). Preservation of STEMI systems of care resulted in an overall lower in-hospital mortality rate than predicted, although opportunities exist to improve treatment delays. Regional differences in mortality rates require further study.

Abstract Background Medical chaperones are authorized individuals present during physical examinations involving the genitals, breasts/chest, or anal areas. The use of medical chaperones may provide an opportunity to improve transgender and gender diverse (TGD) patients’ experiences with sensitive examinations. Aim To examine TGD adult patients’ preferences and comfort for having a medical chaperone and whether TGD-specific characteristics, social anxiety symptoms, and feelings of medical mistrust are associated with preference for having a medical chaperone present during a sensitive physical examination. Methods This study used a cross-sectional survey that randomly sampled adult patients from a gender clinic in the Midwest region of the U.S. A total of 420 surveys were mailed. Sixty-two surveys were returned undeliverable, 358 reached recipients; 151 were returned (42.1% response rate). The survey included items related to demographics, gender-related anatomical dysphoria, social anxiety symptoms, feelings of medical mistrust, and preference and comfort towards medical chaperones. Results Among 149 respondents, 74 (49.7%) reported comfort for the idea of having a medical chaperone present during a sensitive physical examination, 50 (33.6%) reported neutral comfort, and 25 (16.8%) reported discomfort. Among 147 respondents, 89 (60.5%) endorsed a preference for a female medical chaperone. We found no associations between gender-related anatomical dysphoria or social anxiety symptoms and comfort for having a medical chaperone, or the gender preference for a medical chaperone. Medical mistrust was associated with lower comfort with having a medical chaperone present during a sensitive physical examination. Clinical Implications Routinely offering medical chaperones, especially female chaperones, is like to be generally acceptable to most TGD patients. These findings may inform clinic policies on providing medical chaperones during sensitive examinations. Strengths and Limitations This study is the first to examine TGD preferences for medical chaperones. Findings are limited by a single site, homogeneous sample, cross-sectional design, and reliance on hypothetical rather than observed examinations. Conclusion TGD adults report comfort with the concept of having a medical chaperone during sensitive examinations and most would prefer the chaperone to be female. Preference for having a medical chaperone present during a sensitive physical exam is not likely influenced by gender dysphoria or social anxiety.

TPS11585 Background: Soft tissue sarcomas (STS) with genomic complexity are often aggressive but may be sensitive to further genotoxic stress. Leiomyosarcoma (LMS), a common STS, frequently harbors genomic complexity and DNA damage response (DDR) dysregulation. Preclinical data showed hyper-dependency on DNA-PK-mediated non-homologous end joining (NHEJ) DDR, and low-dose liposomal doxorubicin (LD-LPD) synergized with the DNA-PK inhibitor peposertib to inhibit tumor growth in LMS models. We hypothesize that a low, sensitizing dose of LPD enhances DNA damage and safely synergizes with peposertib in LMS and other genomically complex STS. Methods: This phase 1, open label, multicenter dose escalation and dose expansion study (NCT05711615) evaluates LD-LPD given intravenously (IV) on day 1 of 28-day cycles with peposertib given orally (PO) twice daily (BID) continuously (Table). Up to 18 patients (pts) over 18 years-old with advanced or unresectable LMS, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, and synovial sarcoma, ECOG performance status ≤2, who received ≥1 prior line of systemic therapy (including anthracycline ≤300 mg/m 2 ) are eligible for dose escalation. Dose expansion will include 12 pts with LMS. The primary objective is to determine the recommended phase 2 dose of LPD+peposertib based on the dose limiting toxicity rate. The Bayesian Optimal Interval (BOIN) design will inform dose escalation decisions. Secondary endpoints for the expansion cohort include adverse event rate, progression-free survival, and objective response rate per RECIST v1.1. Potential predictive biomarkers and changes in DDR biomarkers will be evaluated on biopsies during screening and at cycle 1 day 7. Circulating tumor DNA (ctDNA) collected at baseline (dose escalation and dose expansion), on treatment and at progression (dose expansion) will be correlated with disease activity and response. This trial activated on 8-May-2023 through the Experimental Therapeutics Clinical Trials Network (ETCTN) and is enrolling at select sites in the United States. Dose escalation is ongoing as of January 2025. Clinical trial information: NCT05711615 . Planned dose levels for dose escalation. Dose Escalation Schedule Dose Level Dose Liposomal doxorubicin Peposertib (tablet) -1 10 mg/m 2 IV 50 mg PO BID 0* 10 mg/m 2 IV 100 mg PO BID +1 10 mg/m 2 IV 150 mg PO BID +2 10 mg/m 2 IV 200 mg PO BID +3 15 mg/m 2 IV 200 mg PO BID +4 20 mg/m 2 IV 200 mg PO BID *Starting dose.

e13701 Background: The optimal therapeutic strategy for advanced epithelial ovarian cancer (EOC) — primary debulking surgery (PDS) followed by adjuvant chemotherapy vs. neoadjuvant chemotherapy (NACT) followed by interval debulking surgery — remains debated. NACT is often chosen for unresectable disease, typically identified only during surgery. This study aims to develop a deep learning (DL) model to predict tumor resectability from pre-operative computed tomography (CT) scans. Methods: We retrospectively included EOC patients, FIGO stage III-IV, who underwent PDS between 01/ 2016 and 12/2023 at the European Institute of Oncology, Milan, Italy. The dataset included anonymized portal venous phase contrast-enhanced CT scans. Residual tumor (RT) annotations were extracted from operative reports and categorized as optimal RT (< 1cm) and suboptimal RT (≥1cm). A DL segmentation model (based on open-source TotalSegmentator) was used to identify pelvic/abdominal organ volumes and to remove couch artifacts. The dataset was split into training/validation (80%) and testing (20%) sets. A pre-trained Vision Transformer (ViT) encoder was adapted for 3D imaging, converting CT volumes into features refined by an attention mechanism and classified as optimal RT or suboptimal RT . We trained two ViT configurations (vit-base-patch16-224 and dinov2-small-imagenet1k-1-layer) and compared them with DenseNet121, a widely used Convolutional Neural Network (CNN) for image classification. Performance metrics included accuracy and F1 score. Results: Out of 521 patients, 416 (80%) had optimal RT and 105 (20%) suboptimal RT , the proportion being respected througouth the training/validation and testing groups. The median age at diagnosis was 60.0 years (IQR, 53.0-67.0). ViT models showed better performance compared to CNN in terms of accuracy (0.80 and 0.77 vs. 0.62) and F1 score (0.43 and 0.33 vs. 0.12). Conclusions: A pioneering ViT-based model was capable to predict tumor resectability from pre-operative CT scans in patients with advanced EOC. This improvement in performance, compared to CNN, might be due to the ViTs' ability to capture long-range dependencies and global context, which are crucial for predicting tumor resectability. In contrast, CNNs are limited by localized feature extraction and inductive bias, hindering their ability to capture the complex spatial relationships. By addressing the limitations of current radiological assessments, the model has the potential to serve as a clinical decision-support tool, enabling personalized management strategies for patients. Future work will focus on further improving the model performance.

Background and Objectives The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels and genetic variation related to vitamin D receptor (VDR) binding. The objective was to identify whether VDR binding variants (VDR-BVs) previously implicated in adult-onset MS were associated with pedMS using genetic instrumental variables (GIVs). Methods Using previously identified VDR-BVs to construct individual GIVs with two-sample MR, we investigated associations with pedMS in 725 cases and 592 controls of European ancestry from the US Network of Pediatric MS Centers. Associations between each VDR-BV and pedMS were estimated using logistic regression adjusting for the first three genome-wide principal components. A significant interaction between a VDR-BV and 25(OH)D GIV provided evidence for a causal association unbiased by pleiotropy. Results One VDR-BV, rs2531804, previously associated with adult-onset MS, was also significantly associated with pedMS after multiple testing correction. Discussion This study is the first to use VDR-BVs from previous MR studies to demonstrate causal differences in VDR binding at a locus contributing to pedMS susceptibility.

Abstract Rationale: The Deterioration Index (DTI) may serve as a crucial tool for predicting adverse patient outcomes; however, there is a paucity of literature attempting to externally validate this tool in specific clinical scenarios. In this study, we analyzed the relationship between DTI scores during rapid response team (RRT) activations and subsequent ICU transfer, initiation of goals of care (GOC) conversations, and 90-day mortality. Methods: This was a retrospective single-center review of adult patients who had an RRT activation while hospitalized between January 1, 2023 and December 31, 2023. This study was approved by our hospital institutional review board. Deterioration scores (0-100) were recorded every 15 minutes during the RRT event, and the highest score of each encounter was selected for analysis. The primary outcome was transfer to the ICU as a direct result of the RRT activation. Secondary outcomes included GOC discussions following RRT activation and 90-day mortality. GOC discussions, defined as physician-led conversations that specifically addressed code status, treatment priorities, or broader goals of care, met criteria only if initiated within 72 hours of the analyzed RRT activation. Logistic regression was used to assess the relationship between DTI scores during RRT activations and the aforementioned variables. Results: A total of 1643 patients were included in the analysis. For every 1-point increase in the deterioration score, the odds of ICU transfer increased by 2.7% (OR: 1.027, CI: 1.021-1.034, p&lt;0.0001), the odds of a goals of care discussion within 72 hours increased by 3.3% (OR: 1.033, CI: 1.025-1.040, p&lt;0.0001), and the likelihood of mortality within 90 days increased by 2.6% (OR: 1.026, CI: 1.019-1.033, p&lt;0.0001). Conclusion: Our findings contribute to external validation of DTI predictive value during RRT events. DTI scores were associated with key clinical outcomes, including ICU transfer and 90-day mortality. There was also an association between DTI scores and the likelihood of physician-led GOC discussions, suggesting that DTI may demonstrate predictive value not only of patient outcomes, but also the likelihood of specific non-medical physician actions. Further validation of these scores in prospective studies, specifically in the context of acute decompensation events, could help facilitate the integration of DTI-based RRT interventions into routine hospital practice.

Abstract Rationale: Medical trainees are often involved in the care of hospitalized patients, yet there are minimal data about correlation of trainee involvement with outcomes for patients with rapid response team (RRT) activations. Methods: This was a retrospective single-center review of adult patients on a primary medicine service who had an RRT activation between January 1, 2023 and December 31, 2023. This study was approved by our hospital institutional review board. Patients were included if they were at least 18 years old and had a hospitalization with an RRT activation. Outcomes analyzed included transfer to the ICU, 90-day mortality, and goals of care discussions. A subset analysis was performed of patients who remained on the floor after RRT. Statistical analysis was performed with Pearson's chi-square and Kruskal-Wallis tests. Results: We analyzed 1686 adult patients who had an RRT activation within the study timeframe. Mean age was 67.3 years (SD 16.8), 792 (47.0%) were female, and 1489 (88.3%) identified as white. Trainees were involved with 1016 (60.3%) patients; 935 of these were on an internal medicine team and 81 were on a family medicine team. Patients were more likely to transfer to the ICU if they were on a primary floor team with trainee involvement (p = 0.006). There was no difference in goals of care discussion occurrence prior to RRT (p = 0.257) or 90-day mortality (p = 0.877). Subset analysis of patients who remained on the floor after RRT was performed. There was no difference in occurrence of goals of care discussions after RRT (p = 0.169), code status change (p = 0.237), or transition to comfort care (p = 0.381) for patients on teams with trainee involvement and those without. Of the 925 patients who remained on the floor after RRT, goals of care discussion occurred after RRT in 210 (22.7%). Conclusions: In this study, we demonstrate that trainee involvement does not correlate with occurrence of goals of care discussions either before or after RRT activations. Trainee involvement also does not correlate with 90-day mortality for patients with decompensation events. However, patients on teams with trainee involvement are more likely to transfer to the ICU as the result of an RRT activation. It is possible that this reflects the increased complexity of patients who are admitted to teaching services; however, further investigation is needed.

Abstract Introduction: Differentiation syndrome (DS) is a life-threatening adverse drug reaction caused by differentiating agents, including all-trans retinoic acid, arsenic trioxide, inhibitors of mutant isocitrate dehydrogenase (e.g., enasidenib), and the FLT3 inhibitor gilteritinib. The proliferation of differentiated leukemic cells can alter cytokine balance, leading to tissue inflammation, but the pathogenesis remains incompletely understood. We present a case of severe DS in a patient with AML and multi-organ failure. Case: An 80-year-old female with a history of polycythemia vera and newly diagnosed AML, on decitabine, venetoclax, and enasidenib. She was admitted after her first treatment cycle with weakness, altered mental status, and neutropenic fever. Enasidenib was discontinued due to suspected DS, and she was treated with dexamethasone for five days. Three days after discontinuing steroids, her respiratory and mental status deteriorated, leading to a rapid response call and transfer to the ICU for acute hypoxemic respiratory failure. Point of care ultrasound revealed underfilled ventricles and collapsible IVC on inhalation. She became hypotensive and unresponsive, requiring intubation. Initial P/F was 72. PV tool with recruitment showed no low inflexion point but recruitable lung. Laboratory results revealed a WBC of 68.7 x 10⁹/L with 89% blasts which was increased from prior days and acute liver injury with hyperbilirubinemia. A CT scan revealed bilateral consolidations and pleural effusions with interlobular septal thickening. Despite initial oxygenation improvement with prone positioning, she remained hypotensive requiring norepinephrine, vasopressin, angiotensin II, and hydrocortisone. Methylene blue was administered with a favorable response. Leukocytosis worsened, and decitabine and hydroxyurea were initiated due to concern for uncontrolled acute leukemia. She was started on continuous renal replacement therapy (CRRT) for oliguric renal failure. After the fourth dose of decitabine, her shock resolved, urinary output improved, and leukocytosis decreased. However, in the following days, her oxygen requirements escalated, WBC again increased to 120 x 10⁹/L with 80% blasts, and she became hypotensive with signs of myocardial ischemia. She was ultimately transitioned to comfort care. Discussion: This case highlights severe DS following enasidenib administration, which progressed to multi-organ failure. Prompt initiation of systemic glucocorticoids is critical in the management of DS, and this condition should be considered in patients receiving active treatment for acute leukemia who require ICU-level care. Risk factors for DS development and the role of prophylaxis remain areas requiring further research in the context of acute leukemia treatment.