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Abstract Rationale Chronic thromboembolic disease (CTED), which is the result of persistent pulmonary vascular obstruction despite 3 months of anticoagulation, can present with significant functional limitations and exercise intolerance despite normal resting hemodynamics. These patients may experience functional impairment due to exercise-induced pulmonary hypertension, impaired stroke volume augmentation with exercise, ventilatory inefficiency, and/or preload insufficiency. Such exercise-induced pathophysiological abnormalities can significantly impair quality of life and contribute to poor long-term outcomes. Although balloon pulmonary angioplasty (BPA) has shown benefit in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its role in CTED patients with normal resting hemodynamics remains uncertain. This systematic review and meta-analysis evaluated the efficacy of BPA in this population. Methods A systematic search of PubMed, Cochrane, Embase, and Scopus was performed from inception through March 1, 2025. A total of 763 studies were screened, of which 42 full-text articles were assessed: six met the inclusion criteria (four retrospective, two prospective), comprising 98 patients. Results Across the included studies, baseline mean values were 20.81 +/- 3.62 mmHg for mean pulmonary arterial pressure (mPAP), 3.49 +/- 1.42 Wood units for pulmonary vascular resistance (PVR), and 405.72 +/- 108.40 m for the 6-minute walk distance (6MWD). Balloon Pulmonary Angioplasty (BPA) was consistently associated with significant improvements in hemodynamic and functional outcomes; BPA reduced mPAP by 3.40 mmHg and PVR by 0.90 WU, while increasing 6MWD by 31.90 m. These changes were also statistically robust across studies, with pooled standardized mean changes (SMC) of -0.88 for mPAP (95% CI, -1.10 to -0.67; P < .05), -0.68 for PVR (95% CI, -0.87 to -0.49; P < .05), and 0.29 for 6MWD (95% CI, 0.13 to 0.45; P < .05). Study-level effect sizes for 6MWD ranged from 0.19 to 0.54 (Figure 1A). Functional improvements were further demonstrated by shifts in NYHA class distribution (Figure 1B). Conclusion BPA was associated with meaningful reductions in mPAP and PVR and significant improvements in functional capacity among patients with CTED. These results indicate that BPA could be an effective treatment for certain patients with CTED, though more research is necessary. This abstract is funded by: None

Abstract Rationale Chronic thromboembolic disease (CTED) is characterized by persistent pulmonary vascular obstruction due to unresolved thromboemboli despite at least three months of anticoagulation. Although resting hemodynamics often remain normal, affected patients frequently develop functional limitation due to exercise-induced pulmonary hypertension, ventilatory inefficiency, limited stroke volume augmentation, or preload insufficiency. Such exercise-induced pathophysiological dysregulation can significantly impair quality of life and contribute to poor long-term outcomes. Pulmonary endarterectomy (PEA) is an established treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), offering significant improvements in hemodynamics and survival. Its role in CTED, however, remains unclear. While CTED has traditionally been managed with anticoagulation and supportive therapy, emerging evidence suggests PEA may provide symptomatic and functional benefit in selected CTED patients. Given the ongoing uncertainty regarding the role of PEA in CTED, we performed a systematic review and meta-analysis to define its safety profile and clinical efficacy in this patient subset. Methods A systematic search of PubMed, Cochrane, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar was conducted from database inception to March 1, 2025. Of 2,244 records screened, 34 full-text articles were assessed, and seven met the inclusion criteria. Results Across the included studies, the pooled baseline mean values were 20.48 ± 3.03 mm Hg for mean pulmonary arterial pressure (mPAP), 2.83 ± 1.11 Wood units for pulmonary vascular resistance (PVR), and 397 ± 100.08 m for the 6-minute walk distance (6MWD). Pulmonary Endarterectomy (PEA) was consistently associated with significant improvements in hemodynamic and functional outcomes; PEA reduced mPAP by 3.58 mmHg (pooled Standardized Mean Change (SMC)=-1.03; 95% CI, -1.23 to -0.83; P < .05), PVR by 0.86 Woods units (pooled SMC=-0.86; 95% CI, -1.05 to -0.67; P < .05), while, conversely, increased 6MWD by 37.49 m (pooled SMC, 0.49; 95% CI, 0.32 to 0.67; P < .05). Study-level effect sizes for 6MWD ranged from 0.21 to 1.47 (Figure 1A). This clinical improvement is further reflected in the enhancement of the NYHA functional class, as illustrated in Figure 1B. Conclusion PEA was associated with significant reductions in mPAP and PVR, as well as a considerable improvement in functional capacity in patients with CTED, with robust results across multiple tests for bias, influence, and sensitivity analyses. These findings support PEA as a viable therapeutic option for selected patients with CTED, although further research is warranted. This abstract is funded by: None

TPS9607 Background: The majority of 100,000 annual new U.S. cases of mel consist of localized early-stage disease that undergo wide local excision (WLE) +/- SLN biopsy (SLNB). The tumor draining lymph node is the initial site of immune response including formation of tumor mediated immune suppression and pre-metastatic niches. SLN positivity is a key prognostic factor in early stage mel. Thus, the SLN is a target for local immune intervention to boost the antitumor response. Vusolimogene oderparepvec (RP1) is an intratumorally administered oncolytic immunotherapy with unique potential for neo-adjuvant therapeutic application. RP1 is constructed from a high potency HSV1 strain (RH018A) modified to replicate selectively in tumors (deletion of neurovirulence factors ICP34.5 and ICP47). RP1 encodes GM-CSF and a fusogenic GALV-GP R- protein to maximize oncolytic potency and induce immunogenic cell death. Preclinical and clinical data demonstrate robust antitumor efficacy (including non-injected lesions) of RP1 alone and in combination with checkpoint inhibitors in advanced mel. This trial addresses a crucial gap in understanding the impact of RP1 on SLN dynamics and preventing disease recurrence in high-risk patients (pts). We hypothesize that in pts with high risk, clinically node negative mel (pT3b-T4b), RP1 will reduce rates of SLN positivity as compared to a historic control by favorably reshaping the immune landscape of the primary tumor, SLN, and the peripheral blood. Methods: This is an investigator-initiated, single arm phase 1/2 trial (NCT06216938) designed to assess efficacy and safety of neo-adjuvant RP1 in high-risk, clinically node-negative, non-uveal mel. Eligibility criteria: pT3b, T4a, or T4b non-uveal mel with visible residual tumor or positive biopsy margins, ECOG ≤1, and no prior oncolytic virus therapy. Pts receive 3 doses of neo-adjuvant RP1 (10e6 PFU day 1, 10e7 PFU on days 15 and 21), injected at the primary tumor site followed by standard WLE and SLNB within 35 days of dose 1. Biopsy of residual tumor or archival tumor tissue is obtained pre-RP1 and archival tissue from WLE and SLNB is obtained post-RP1. Blood samples are obtained with each RP1 dose and 3 months post-therapy. Pts are followed for 3 years. Primary endpoint: rate of SLN positivity in the overall cohort. Secondary endpoints: treatment related adverse events (per CTCAE), recurrence free survival, and overall survival. Exploratory endpoints: immunophenotype and microenvironment of the primary tumor, SLN and peripheral blood pre- and post- RP1 (via IHC, IF, and flow cytometry). The observed rate of SLN positivity will be compared to the predicted rate (Melanoma Institute of Australia Prediction Tool for SLN metastatic risk) with a one-sided, one-sample proportion test. Kaplan-Meier estimates will be provided for survival endpoints. The trial is active with 13 of 25 pts enrolled in January 2025. Clinical trial information: NCT06216938 .

OBJECTIVE Management of locally invasive colorectal carcinoma at any stage currently involves surgical excision followed by chemoradiotherapy; however, the prognosis is poor, with a 5-year overall survival (OS) of only 5%. Failure to achieve gross-total resection is associated with poorer OS, and patients with residual tumor postresection (R1 or R2 resection) have a median OS of 7 months compared with 23 months in those who undergo resection with negative margins (R0 resection). For tumors that have invaded the sacrum, sacrectomy becomes necessary to achieve R0 resection. The objective of this study was to provide a descriptive multicenter account of resection for locally invasive colorectal carcinoma with sacral invasion, focusing on the association of tumor morphometry with surgical planning and perioperative outcomes. METHODS Demographic, comorbidity, clinical, tumor-specific, operative characteristic, and outcome data were collected on all patients who underwent resection of colorectal carcinoma with concurrent sacral resection between January 2005 and May 2022. Patients were grouped into those having undergone surgery for purely palliative intent, or those with resection with attempt at local control and dichotomized into level of osteotomy (either proximal or distal to the S2–3 level). RESULTS Twenty-two patients (median age 50.5 [IQR 43.3–60.0] years, 54.5% female) underwent sacrectomy for colorectal carcinoma. Operative records indicated intent for local control in 14 patients and palliative in the remaining 8 patients. Palliative surgical intent was based primarily on the presence of distant metastases. There was no significant difference in median local progression-free survival between patients undergoing osteotomy proximal to the S2–3 level and those undergoing osteotomy distal to the S2–3 level. CONCLUSIONS En bloc resection is believed to offer the best local control in patients with locally invasive colorectal carcinoma. The present descriptive series highlights outcomes of en bloc resection with partial or full sacrectomy in patients with tumors showing local extension into the sacrum. Complications are common, most often in the form of wound dehiscence or infection, and many patients require placement in a rehabilitation or intermediate-care facility upon discharge. However, for those with stage III (locally aggressive) disease, median OS exceeds 16 years, suggesting that such aggressive management with en bloc resection may be warranted in properly selected patients.

Cancer immunotherapy—including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)—has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies. Recent advancements as well as novel approaches to address the limitations of current treatments are discussed here, with a specific focus on ICI and ACT.

Abstract Background In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS) from initiation of 2L adjuvant dab/tram (RFS-2), analyzed via Kaplan-Meier methods. Results Thirty-eight patients were included (median age 50 years, 63% male, 87% stage III, median follow-up 19 months from 2L dab/tram initiation). Median dab/tram duration was 10.1 months (range: 1 day–22.7 months), with half discontinuing due to progression or adverse events. Median (95% CI) RFS-2 was 18.9 (14.9–28.1) months, with 91%, 81%, and 58% remaining relapse-free at 6, 12, and 18 months, respectively. Most patients remained distant metastasis-free at 6, 12, and 18 months (97%, 85%, and 71%, respectively). Two patients were deceased at the last follow-up, with 97% alive at 18 months. Conclusions Over 80% of patients remained relapse- and metastasis-free at 12 months after 2L dab/tram initiation, with only 2 deaths observed. Dab/tram appears to have activity in the 2L adjuvant setting, although more follow-up is required.

Background: Hip arthroscopy has seen a significant surge in utilization, but complications remain, and optimal functional outcomes are not guaranteed. Artificial intelligence (AI) has emerged as an effective supportive decision-making tool for surgeons. The purpose of this systematic review was to characterize the outcomes, performance, and validity (generalizability) of AI-based prediction models for hip arthroscopy in current literature. Methods: Two reviewers independently completed structured searches using PubMed/MEDLINE and Embase databases on August 10, 2022. The search query used the terms as follows: (artificial intelligence OR machine learning OR deep learning) AND (hip arthroscopy). Studies that investigated AI-based risk prediction models in hip arthroscopy were included. The primary outcomes of interest were the variable(s) predicted by the models, best model performance achieved (primarily based on area under the curve, but also accuracy, etc), and whether the model(s) had been externally validated (generalizable). Results: Seventy-seven studies were identified from the primary search. Thirteen studies were included in the final analysis. Six studies (n = 6,568) applied AI for predicting the achievement of minimal clinically important difference for various patient-reported outcome measures such as the visual analog scale and the International Hip Outcome Tool 12-Item Questionnaire, with area under a receiver-operating characteristic curve (AUC) values ranging from 0.572 to 0.94. Three studies used AI for predicting repeat hip surgery with AUC values between 0.67 and 0.848. Four studies focused on predicting other risks, such as prolonged postoperative opioid use, with AUC values ranging from 0.71 to 0.76. None of the 13 studies assessed the generalizability of their models through external validation. Conclusion: AI is being investigated for predicting clinical outcomes after hip arthroscopy. However, the performance of AI models varies widely, with AUC values ranging from 0.572 to 0.94. Critically, none of the models have undergone external validation, limiting their clinical applicability. Further research is needed to improve model performance and ensure generalizability before these tools can be reliably integrated into patient care. Level of Evidence: Level IV . See Instructions for Authors for a complete description of levels of evidence.

Introduction Revision total elbow arthroplasty (TEA) is indicated for component loosening, periprosthetic joint infection, and fractures. Previous investigations into revision TEA complications have small sample sizes and limited exploration of acute complications. This study aims to characterize the 30-day complications and associated demographics of patients undergoing revision TEA using a large national database. Methods The 2015–2020 American College of Surgeons National Surgical Quality Improvement Program database was used to identify all revision TEA patients. Results The analysis included 158 patients (average age 62.6 years). The overall complication rate was 13.9% ( n = 22). The most common 30-day complications were organ/space surgical site infection (3.8%, n = 6), unplanned readmission (3.2%, n = 5), intraoperative or postoperative transfusion (3.2%, n = 5), and unplanned reoperation (1.9%, n = 3). Patients with a history of dyspnea or steroid/immunosuppressant use for a chronic condition had significantly higher rates of bleeding requiring transfusion ( p = .029 and p = .021, respectively). Additionally, patients aged 80 years or older had a significantly higher rate of unplanned readmission ( p = .032). Conclusion Revision TEA has a 13.9% rate of complications within 30-days of surgery, with most involving surgical site infection, unplanned readmission, and blood transfusion. Level of Evidence IV.

AbstractBackgroundPhosphide metal poisoning results in tens of thousands of fatalities per year worldwide. The mortality in critically ill patients often exceeds 50%. The available treatment is supportive and there is no antidote. Dialysis is recommended to treat advanced complications but has not been prescribed early in the process. In this study we report our experience in using dialysis in the early hours of presentation of the patients and suggest it can favorably improve the prognosis. We also draw attention to the risk of suicide under conditions of chronic conflict such as those in northwestern Syria, and to the lack of necessary mental health support for patients after suicide attempts.MethodsRetrospective review of records of patients poisoned with aluminum phosphide and admitted to critical care facilities in northwestern Syria between July 2022 and June 2023.ResultsDuring the observation period 16 cases were encountered. Suicide was the reason of the poisoning in 15 patients, the median patient age was 18 years and over two thirds of the patients were female. Early dialysis was used in 11 patients who were critically ill and their mortality rate was 18%.ConclusionsPhosphide metal poisoning is common in the disasters stricken area of northwestern Syria. Most cases are suicidal and impact young females. Early dialytic interventions may favorably impact the outcomes.

AbstractBackgroundInvasive hemodynamics are fundamental in assessing patients with advanced heart failure (HF). Several novel hemodynamic parameters have been studied; however, the relative prognostic potential remains ill‐defined.HypothesisAdvanced hemodynamic parameters provide additional prognostication beyond the standard hemodynamic assessment.MethodsPatients from the PRognostic Evaluation During Invasive CaTheterization for Heart Failure (PREDICT‐HF) registry who underwent right heart catheterization (RHC) were included in the analysis. The primary endpoint was survival to orthotopic heart transplant (OHT) or durable left ventricular assist device (LVAD), or death within 6 months of RHC.ResultsOf 846 patients included, 176 (21%) met the primary endpoint. In a multivariate model that included traditional hemodynamic variables, pulmonary capillary wedge pressure (PCWP) (OR: 1.10, 1.04−1.15, p < .001), and cardiac index (CI) (OR: 0.86, 0.81−0.92, p < .001) were shown to be predictive of adverse outcomes. In a separate multivariate model that incorporated advanced hemodynamic parameters, cardiac power output (CPO) (OR: 0.76, 0.71−0.83, p < .001), aortic pulsatility index (API) (OR: 0.94, 0.91−0.96, p < .001), and pulmonary artery pulsatility index (OR: 1.02, 1.00−1.03, p .027) were all significantly associated with the primary outcome. Positively concordant API and CPO afforded the best freedom from the endpoint (94.7%), whilst negatively concordant API and CPO had the worst freedom from the endpoint (61.5%, p < .001). Those with discordant API and CPO had similar freedom from the endpoint.ConclusionThe advanced hemodynamic parameters API and CPO are independently associated with death or the need for OHT or LVAD within 6 months. Further prospective studies are needed to validate these parameters and elucidate their role in patients with advanced HF.