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TPS615 Background: The TAILORx and RxPONDER trials demonstrated that RS identifies many postmenopausal pts with node-neg and node-pos BC and RS ≤25, who do not benefit from addition of ACT to endocrine therapy (ET). Both trials also showed that certain subsets of premenopausal pts (node-neg/high clinical risk/RS 16-20, node-neg/RS 21-25, and node-pos/RS ≤25) benefited from adding ACT to ET. Most premenopausal pts in these trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR+/HER2- BC in the SOFT/TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, we developed OFSET, a phase III, multicenter clinical trial comparing OFS+ET v ACT+OFS+ET. Methods: We hypothesize that addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR+/HER2- tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival, overall survival, distant recurrence-free interval, breast cancer-free interval, and health-related quality of life (HRQOL). Pts must be node-neg with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS ≤25. Stratification is by nodal status/RS status (pN0 RS 16-25 v pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 v ≥40). Pts are randomized after surgery to either OFS+ET or ACT+OFS+ET v ET is an aromatase inhibitor (AI). Choice is per investigator discretion; tamoxifen is allowed if AI is not tolerated or if OFS is incomplete. Radiotherapy will be administered per investigator discretion per protocol guidelines. The HRQOL sub-study will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score between arms, as well as increased pain severity (PROMIS). Blood and tumor specimens will be collected for future research. Accrual of 3,960 pts is anticipated to be completed in 7 yrs, 7 mos. Per NSABP B-28 and RxPONDER data, 5yr IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on TAILORx data, 5yr IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of pts to be pN0 and 44% pN1, and a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET v OFS+ET, with one-sided α of 0.025 and 80% power, will require 380 IBCFS events, expected to occur~11 yrs after study initiation. OFSETwas activated Aug 2023. As of 1-6-25, accrual is: 188/3,960. NCT #: NCT05879926. Support: U10CA180868, -80822, UG1CA189867, U24CA196067. Clinical trial information: NCT05879926 .

ABSTRACT Background Advancements in organ transplant technology are pushing global transplant capabilities to new heights. However, challenges persist in pediatric surgical and medical transplant fellowship training, primarily due to a limited number of adequate training programs and gaps in education. Addressing these gaps is essential for improving patient outcomes and advancing the field of pediatric transplantation. Methods An international survey was distributed to 416 pediatric transplant fellows via multiple global transplant associations. The 29‐question survey, available in English and Spanish, assessed current clinical knowledge, training satisfaction, and preferred learning formats. The survey received responses from 237 pediatric transplant fellows. Results One of the key findings was that respondents felt most confident in their pre‐transplantation clinical knowledge. About 75.5% of fellows reported being extremely or very aware of pre‐transplant workups and assessments. However, significant gaps were identified in other areas of training. Notably, 24% of respondents felt extremely knowledgeable about the side effects of immunosuppression, and only 22.8% were very confident in managing acute rejection. Fellows expressed strong interest in dynamic educational formats, particularly clinical case discussions (88.8%). Preferred methods to enhance training included continuing medical education (64.6%), hands‐on workshops, and support for transition protocols and psychosocial counseling. Conclusion This global survey highlights critical educational gaps in pediatric transplant fellowship training and identifies preferred learning methods among fellows. Targeted improvements such as standardized curricula, case‐based learning, interdisciplinary collaboration, and accessible continuing education are essential to enhance training. These strategies will ensure that future transplant professionals are well‐equipped to deliver high‐quality care across diverse healthcare settings.

Abstract Background Classic progressive supranuclear palsy RS syndrome (PSP‐RS) is characterized by early postural instability/falls and vertical supranuclear gaze palsy, although other signs/symptoms can occur, for example, axial rigidity, bradykinesia, and cognitive dysfunction. The Movement Disorders Society‐PSP (MDS‐PSP) criteria consider probable PSP‐RS a homogenous syndrome, but this has not been tested. Objectives We aim to investigate relationships between signs/symptoms of PSP‐RS beyond its core features and determine whether PSP‐RS is a homogeneous syndrome. Methods 118 participants who met MDS‐PSP criteria for probable PSP‐RS were analyzed. All participants received an independent clinical diagnosis based on clinical judgment. We first performed a Network Analysis using qgraph with Spearman's correlation to quantify relationships between 16 signs/symptoms followed by a k‐means clustering analysis using the same signs/symptoms to identify possible heterogeneity of the PSP‐RS designation. Results Five network clusters were identified, reflecting: (1) tremor, (2) sensitivity to bright light, (3) oculomotor function, (4) cognition, and (5) akinetic‐rigidity‐praxis. Worse akinetic‐rigidity was associated with better oculomotor function, but worse cognition. Cluster analysis revealed two clusters. Cluster I ( n = 89) had more severe clinical features than Cluster II ( n = 29). Cluster II had a higher frequency of participants (37.9%) clinically judged as not PSP‐RS: these participants were less likely to have PSP pathology on autopsy ( P = 0.03). Conclusions Some signs/symptoms of PSP‐RS strongly associate and are more likely to co‐occur. PSP‐RS, as defined by the MDS‐PSP criteria includes a subset of participants not clinically judged as PSP‐RS who are less likely to have PSP pathology.

Background: Osteochondral allograft transplant and autograft transplant for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. Purpose: To evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplant for femoral head defects and identify any risk factors that may lead to conversion to total hip arthroplasty (THA). Study Design: Case series; Level of evidence, 4. Methods: All patients who underwent osteochondral allograft or autograft transplant for femoral head defects across 2 institutions were analyzed. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Complications and reoperations were recorded. Patients were assessed radiographically preoperatively and at final follow-up for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplant, 8 osteochondral autograft transplant). The mean follow-up for the allograft and autograft cohorts was 2.8 and 9.5 years, respectively. The mean defect size for patients who underwent allograft and autograft transplant was 2.8 × 2.1 cm and 1.6 × 1.0 cm, respectively. The mean mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, and for the autograft cohort were 87.6, 92.7, 83.1, and 82.0, respectively. No significant difference in outcomes was noted for patients who underwent femoral head allograft versus nonorthotopic femoral condyle allograft transplant. For the allograft cohort, 4 patients (21.1%) underwent conversion to THA at a mean of 1.9 years. Of the remaining 15 allograft patients, only 1 patient (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent conversion to THA. Conclusion: Osteochondral allograft and autograft transplant for femoral head defects demonstrated overall favorable clinical outcomes and rates of conversion to THA. Additionally, nonorthotopic femoral condyle allografts demonstrated similar outcomes to femoral head allografts. Both osteochondral allograft and autograft transplant should be considered for patients with focal femoral head defects.

Abstract Introduction: Chronic Obstructive Pulmonary Disease (COPD) exacerbations increase inflammation, immobilization, and thrombotic risk, leading to a higher incidence of pulmonary embolism (PE). This study evaluates the incidence and risk of PE in patients with acute exacerbations of COPD (AECOPD) compared to those without exacerbations. Methodology: This retrospective cohort study utilized data from 94 healthcare organizations, identifying two cohorts: patients with AECOPD and those without exacerbations. Inclusion was based on ICD-10-CM codes, and individuals with malignancies, coagulation disorders, or prior PE were excluded. Propensity score matching was performed to balance the cohorts on demographics, clinical characteristics, and medications. The primary outcome was PE incidence, analyzed using risk differences, risk ratios, odds ratios, and Kaplan-Meier survival analysis to evaluate mortality outcomes associated with PE. Results: After matching, both cohorts comprised 174,345 patients each. The mean age was approximately 73 years, with a slight female predominance (49.0% in AECOPD vs. 49.3% in non-AECOPD). The incidence of PE was significantly higher in the AECOPD cohort (15%) compared to the non-AECOPD cohort (8%) (p < 0.001). Specifically, 2,162 patients (1.3%) in the AECOPD cohort developed PE, compared to 1,467 patients (0.9%) in the non-AECOPD cohort. The risk difference was 0.004 (95% CI: 0.003, 0.005; p < 0.001). The risk ratio for PE in the AECOPD cohort was 1.477 (95% CI: 1.382, 1.577), and the odds ratio was 1.483 (95% CI: 1.387, 1.585). Survival analysis revealed a probability of 95.23% in the AECOPD cohort and 97.15% in the non-AECOPD cohort, with significant differences (χ² = 153.746, df = 1, p < 0.001). The hazard ratio for mortality associated with PE was 1.517 (95% CI: 1.419, 1.621). Conclusion: Patients with AECOPD have a significantly higher incidence of pulmonary embolism compared to those without exacerbations. PE is often overlooked in AECOPD patients due to the overlap in clinical symptoms, making timely diagnosis and treatment challenging. This can result in delayed management and poor outcomes. Therefore, it is crucial to enhance understanding of the clinical manifestations, diagnosis, and treatment of COPD complicated by PE to improve diagnostic accuracy, ensure timely intervention, and optimize patient prognosis.

Abstract Introduction: Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, particularly in its moderate to severe cases, where effective management is crucial to improving patient outcomes. The integration of inhaled corticosteroids with long-acting β2-adrenoceptor agonists and long-acting muscarinic antagonists in fixed-dose combinations has emerged as a cornerstone of therapy. This study evaluates the efficacy of two triple therapy regimens — Glycopyrrolate, Budesonide, and Formoterol Fumarate (GLY/BUD/FOR) and Fluticasone Furoate, Vilanterol, and Umeclidinium (FF/VI/UMEC) —in adults aged 45 and older with diagnosed COPD with FEV1/FVC < 70% to assess the impact of these regimens on the preventing COPD exacerbations and acute hypoxemic respiratory failure. Methods: A retrospective cohort analysis was conducted using the TriNetX database. Patients with moderate to severe COPD and FEV1/FVC < 70% were identified based on ICD codes, and two cohorts were formed based on the prescribed inhaler therapy: GLY/BUD/FOR and FF/VI/UMEC. Patients with comorbid asthma, heart failure, or pneumonia were excluded. A 1:1 propensity-score matching (PSM) analysis was performed to balance covariates such as age, gender, smoking status, and baseline lung function to minimize confounding and bias. Post-matching, both had 16,052 patients. Ultimately, 23,331 patients (FF/VI/UMEC: 11,234, GLY/BUD/FOR: 12,097) with a mean age of 67.4 ± 10.1 years and 55.3% males were included. Results: Among groups, 10.4% of patients on FF/VI/UMEC experienced COPD exacerbations compared to 6.7% on GLY/BUD/FOR (Risk Ratio: 1.55, 95% CI: 1.42-1.69, p < 0.001). Kaplan-Meier analysis showed a lower survival probability in the FF/VI/UMEC group (77.7% vs. 83.9%, p < 0.001). For acute respiratory failure, 3.5% of patients on FF/VI/UMEC experienced this outcome compared to 2.8% on GLY/BUD/FOR (Risk Ratio: 1.28, 95% CI: 1.12-1.45, p = 0.003). Conclusion: Our study suggests that FF/VI/UMEC demonstrated an increased risk of COPD exacerbations and acute hypoxic respiratory failure compared to the group receiving GLY/BUD/FOR. This indicates that GLY/BUD/FOR may provide enhanced protective benefits in patients with moderate to severe COPD, improving disease management and minimizing healthcare resource utilization. Further studies are warranted to explore the long-term benefits and potential mechanisms underlying the observed differences.

Abstract Background: Pulmonary rehabilitation (PR) is a comprehensive intervention and essential component for integrated care with patients with chronic respiratory diseases, especially Chronic Obstructive Pulmonary Disease (COPD). American Thoracic Society (ATS) strongly recommends PR for patients with COPD after exacerbation. PR has been shown to reduce mortality, improve quality of life, and decrease hospital readmissions in patients with COPD. Despite these benefits, access to PR remains unevenly distributed, particularly among racial and ethnic minorities. This study explores racial and ethnic disparities in PR utilization among COPD patients with a history of exacerbations. Methods: Utilizing data from the TrinetX Research Network, we examined two cohorts of COPD patients. Cohort 1 (N=493) consisted of patients with COPD and prior exacerbations who received PR, while Cohort 2 (N=457,573) included similar patients who did not receive PR. Demographics, specifically, race and ethnicity, were statistically analyzed to assess the presence and significance of disparities, using chi-square tests and standardized mean differences (SMD) to provide a comparative framework.Results:493 patients were in the PR group and 457,573 patients in the non-PR group, comprising 458,066 patients across both cohorts. Among the 493 patients in the PR cohort, the largest group was categorized as Other Race (192 patients, 38.9%, p < 0.001, SMD = 1.040), followed by White patients (154 patients, 31.2%, p < 0.001, SMD = 0.899). Black or African American and Asian patients were both minimally represented, with 10 patients each (2.0%, p < 0.001, SMD = 0.319 and SMD = 0.034, respectively), while 137 patients (27.8%, p < 0.001, SMD = 0.349) were of Unknown Race. In contrast, the non-PR cohort, comprising 470,239 patients, had a substantially higher proportion of White patients (330,409 patients, 72.2%) and a significantly greater representation of Black or African American individuals (42,573 patients, 9.3%, p < 0.001, SMD = 0.319) and Hispanic or Latino individuals (13,709 patients, 3.0%, p < 0.001, SMD = 0.249) compared to the PR cohort. Conclusion: This study highlights significant disparities in the utilization of PR among COPD patients, with underrepresented racial and ethnic groups demonstrating lower access to this intervention. These findings highlight the need for targeted strategies to address potential barriers to PR, promoting equitable access across diverse populations. Further investigation into structural and socioeconomic factors influencing PR access will be crucial to fostering inclusive care and reducing healthcare disparities in COPD management.

Abstract Introduction: Obesity's increasing prevalence significantly impacts Intensive Care Unit (ICU) patient outcomes, especially for those requiring prolonged mechanical ventilation. This study investigates the effect of Body Mass Index (BMI) on mortality and complications—such as acute respiratory distress syndrome (ARDS), pulmonary embolism (PE), and deep vein thrombosis (DVT)—in ICU patients intubated for over 96 hours. Methods: We conducted a retrospective cohort study using the TriNetX database to identify patient populations with relevant ICD codes. Patients who had received anticoagulation and had been on mechanical ventilation for more than 96 hours were included. Cohort 1 consisted of patients with a BMI of 30-44.9 kg/m² (n = 70,379), and Cohort 2 included patients with a BMI of 18.5-29.9 kg/m² (n = 111,054). Both cohorts were matched using propensity score matching (PSM), resulting in balanced groups of 47,233 patients. The mean age was 64.3 ± 15.1 years in Cohort 1 and 64.5 ± 16.5 years in Cohort 2, with a male predominance of 57.9% in both cohorts after matching. Outcomes (mortality, PE, DVT, and ARDS) were identified using ICD-10 codes and analyzed on Days 14, 30, and 90. Results: Higher BMI was associated with increased all-cause mortality across all measured time points. By Day 14, mortality was 23.0% in Cohort 1 versus 19.2% in Cohort 2 (RiskRatio [RR]: 1.196; 95% CI: 1.166-1.226). By Day 90, mortality reached 37.6% in Cohort 1 compared to 32.6% in Cohort 2 (RR: 1.151; 95% CI: 1.132-1.171). Additionally, the risk of developing ARDS was higher in Cohort 1, with statistically significant risk ratios observed on Day 14 (RR: 1.117; 95% CI: 1.020-1.222) and Day 30 (RR: 1.094; 95%CI: 1.010-1.186). PE risk in Cohort 1 significantly increased by Day 30 (RR: 1.119; 95% CI: 1.008-1.243), while DVT risk was also elevated in Cohort 1 at both Day 14 (RR:1.140; 95% CI: 1.037-1.253) and Day 30 (RR: 1.129; 95% CI: 1.040-1.224). Conclusion: Higher BMI in mechanically ventilated ICU patients intubated for more than 96 hours is associated with increased mortality and a higher incidence of complications, including ARDS, PE, and DVT. This study contributes to our understanding of BMI's impact on ICU outcomes, highlighting critical areas for improved clinical management in this population and the need for targeted interventions in obese ICU patients, such as optimized respiratory support and monitoring for thromboemboliccomplications.

Abstract RATIONALE: Many ICU patients experience physical, psychological, and cognitive impairments following resolution of critical illness, collectively referred to as post-intensive care syndrome (PICS). PICS has become widely recognized within the critical care field, but how to screen for PICS does not currently have consensus. Development of a validated, concise PICS screening tool would allow for rapid identification of this vulnerable and understudied population. Therefore, this study's goal was to develop and evaluate a screening tool to identify patients at risk for PICS. METHODS: We performed a prospective cohort study in a quaternary academic hospital. We included adults ≥ 18 years old with ≥48 hours spent in an ICU. Exclusion criteria were admission for suicide attempt, severe cognitive impairment/dementia, life expectancy <3 months, and non-English speaking. We assessed mental, cognitive, and physical function following ICU discharge and at 3 months using Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, Montreal Cognitive Assessment-blind, and Barthel Index. Our team, including critical care physicians, psychiatrists, psychologists, physical and occupational therapists, and nurses, developed a brief 15-item PICS screening tool (5 questions/domain). This tool was administered after patients were discharged from ICU stay to general care to assess its effectiveness in predicting impairments in all 3 domains at discharge and again at three months after hospital discharge, in comparison to previously mentioned validated questionnaires. Youden index statistical methods were used to determine potential “cutoff” values (scores) for the tool to maximize sensitivity and specificity. RESULTS: A total of 194 patients from 6 ICUs were recruited and completed the initial questionnaire, and 109 (56%) patients completed 3-month follow-up. Median age was 65 years (IQR 57-72) and 49% (95/194) were female. Screening tool is depicted in Figure 1. Overall, the screening tool weakly-to-moderately correlated with continuous outcomes of the validated measures upon ICU discharge and 3-month follow-up. When evaluating sensitivity and specificity for individual domains, the tool had an area under the receiver operating curve of >0.7 for the following domains: cognitive, anxiety, and physical impairments, indicating moderate-to-good sensitivity and specificity. CONCLUSIONS: This PICS screening tool was correlated with validated measures of PICS upon ICU discharge and at 3-month follow-up for all three domains. The tool's strength lies in its concise nature, making it easier for those caring for this patient population to screen for long-term effects of an ICU stay. Our proposed next step is validation of the PICS screening tool in an external cohort.

The growing global freshwater scarcity urgently requires innovative wastewater treatment technologies. This study hypothesized that biomimicry-inspired automated machine learning (AML) could effectively manage wastewater variability through adaptive processing techniques. Utilizing decentralized swarm intelligence, specifically the Respected Parametric Insecta Swarm (RPIS), the system demonstrated robust adaptability to fluctuating influent conditions, maintaining stable effluent quality without centralized control. Bio-inspired oscillatory control algorithms maintained stability under dynamic influent scenarios, while adaptive sensor feedback enhanced real-time responsiveness. Machine learning (ML) methods inspired by biological morphological evolution accurately classified influent characteristics (F1 score of 0.91), optimizing resource allocation dynamically. Significant reductions were observed, with chemical consumption decreasing by approximately 11% and additional energy usage declining by 14%. Furthermore, bio-inspired membranes with selective permeability substantially reduced fouling, maintaining minimal fouling for up to 30 days. Polynomial chaos expansions efficiently approximated complex nonlinear interactions, reducing computational overhead by approximately 35% through parallel processing. Decentralized swarm algorithms allowed the rapid recalibration of system parameters, achieving stable pathogen removal and maintaining effluent turbidity near 3.2 NTU (Nephelometric Turbidity Units), with total suspended solids consistently below 8 mg/L. Integrating biomimicry with AML thus significantly advances sustainable wastewater reclamation practices, offering quantifiable improvements critical for resource-efficient water management.