Faculty Bibliography

INTRODUCTION/UNASSIGNED:Excess cumulative fluid balance is a common complication impacting critically ill pediatric patients that is associated with worse clinical outcomes. Nevertheless, there are inconsistent practices in recognizing and reducing excess fluid balance. PURPOSE/UNASSIGNED:Assess contextual factors that inform fluid-based practices across four pediatric intensive care units. METHODS/UNASSIGNED:We conducted semi-structured interviews across 4 PICUs from August to October 2025. Through an iterative process informed by prior survey data, we followed the established implementation science Reach, Effectiveness, Adoption, Implementation, Maintenance/Practical Robust Implementation and Sustainability Model framework to develop an interview guide. Questions explored fluid balance recognition and reduction. Participants were recruited using purposive sampling via email recruitment. We used Rapid Assessment Procedures with two independent coders. Thematic saturation was reached within the first round of interviews. RESULTS/UNASSIGNED: = 3). Institutions had balanced numbers of interviews. Theme 1 centered on the limitations of data used for fluid balance recognition, namely that these data are affected by patient variability, rely on subjective exam findings, and depend on inaccurate tools. Theme 2 highlighted insufficient emphasis on limiting unnecessary fluid administration. Theme 3 addressed cultural barriers including educational gaps, lack of standardization, entrenched unit practices, and insufficient communication. DISCUSSION/UNASSIGNED:These themes highlight the need for accurate data reporting, shifts in emphasis of fluid management, and cultural/systemic changes. We theorize that these suboptimal approaches to fluid balance management could inform clinical decision support tools, research priorities, and quality improvement initiatives.

PURPOSE/OBJECTIVE:Mobile health cardiac rehabilitation may improve access to care among older adults with ischemic heart disease, but engagement remains poorly understood. We analyzed weekly engagement data from the RESILIENT (Rehabilitation Using Mobile Health for Older Adults with Ischemic Heart Disease in the Home Setting) trial, a large, randomized trial of mobile health cardiac rehabilitation in older adults conducted in the United States. METHODS:Data from 298 intervention participants were analyzed. Weekly engagement was scored from 0 to 11 based on exercise entry (7 points), communication with exercise therapist (2 points), video viewing (1 point), and blood pressure measurement (1 point). Latent class analysis identified digital engagement phenotypes. Participant characteristics were compared, and multivariable logistic regression identified factors associated with phenotype membership. RESULTS:Median age was 71.0 years, 28% were women, 23% were non-White, and 62% were enrolled after elective percutaneous coronary intervention. Latent class analysis identified 3 phenotypes: persistently low (n = 81), intermediate declining (n = 93), and persistently high (n = 124). Participants with persistently low engagement were more likely to be non-White (48% vs 12% vs 15%, P < .001), Medicaid enrolled (22% vs 8% vs 7%, P = .001), have less than high school education (16% vs 4% vs 3%, P < .001), have frailty phenotype (28% vs 10% vs 7%, P < .001), and have a greater mean number of comorbidities (3.1 vs 3.0 vs 2.6; P = .012). After adjustment, non-White race and frailty remained independently associated with low engagement. Improvement in 6-minute walk test distance varied: 20.8 m (low), 29.7 m (intermediate), and 54.5 m (high) (P = .003). CONCLUSIONS:Three distinct digital engagement phenotypes emerged. Persistently low engagement was more common among non-White and frail participants, underscoring ongoing disparities despite efforts to overcome the digital divide.

PURPOSE/UNASSIGNED:Patients with breast cancer isolated local-regional recurrence (iLRR) can benefit from salvage reirradiation (reRT) to provide durable control and prevent further progression. Conformal radiation techniques like pencil beam scanning (PBS) proton beam therapy (PBT) may improve the reRT therapeutic ratio by limiting cumulative dose and improving target region dose delivery. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients between 8/2019-9/2025 treated with PBS-PBT reRT for breast cancer iLRR with prior dose overlap were identified. Clinicopathologic, treatment, and outcomes details were collected. Associations between clinical/treatment factors and time to recurrence and grade (G) ≥2 adverse events (AEs) were evaluated with Fine-Gray models and logistic regression, respectively. Correlations between DVH metrics and late AEs were assessed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS/UNASSIGNED:Seventy patients were identified with median first course (C1), reRT course (C2), and cumulative doses of 53, 50, and 106Gy(RBE), respectively. During C2, 82.2% received comprehensive nodal irradiation. Median follow-up was 30 months. Two- and three-year rates of any recurrence were 14% and 17%, and OS were 100% and 95%, respectively. Maximum acute G2 and G3 AEs occurred in 50% and 7%, and late G2 and G3 AEs in 34% and 10%, respectively. Rib fractures developed in 21.1% and were associated with C1 and C2 chest wall D200cc and C1 rib D10cc. CONCLUSION/UNASSIGNED:In the largest experience of PBT reRT for breast cancer iLRR to date, we report promising disease control and limited severe AEs despite a high-risk patient cohort. We provide dose metrics that can serve as the foundation for reRT dose constraints and be further refined in future reRT investigations.

AIMS/UNASSIGNED:Proximal junctional kyphosis (PJK) remains a major complication after surgery for adult spinal deformity (ASD). While postoperative alignment is a recognized modifiable risk factor, objective methods for selecting the upper instrumented vertebra (UIV), a key modifiable factor, are lacking. We aimed to determine whether preoperative sagittal alignment, specifically cervicothoracic alignment, predicts the risk of PJK, and whether this risk can be mitigated by UIV selection, focusing on factors available at the time of surgical planning. METHODS/UNASSIGNED:From a multicentre, prospective ASD registry, we identified patients who had undergone fusion to the sacrum or pelvis and had an upper (T1-T5) or lower thoracic (T9-L1) UIV, with a two-year or more radiological follow-up, excluding those with a previous fusion over more than four levels. The primary outcome was PJK within two years. Multivariable logistic regression modelled the risk of PJK by UIV region, preoperative C2-T9 pelvic angle (PA), age, sex, and pelvic incidence, testing for interaction between UIV region and C2-T9 PA. Adjusted absolute risk reduction (ARR) and number needed to be exposed (NNEB) were calculated. Multivariable linear regression estimated two-year patient-reported outcome measures, adjusting for baseline scores, age, UIV, and PJK. RESULTS/UNASSIGNED:A total of 627 patients across 20 centres were included (median age 66 years (IQR 59 to 70); 483 (77%) female). The UIV was lower thoracic in 380 (61%) and upper thoracic in 247 (39%) patients. PJK occurred in 149 (39%) lower thoracic and 38 (15%) upper thoracic UIV patients. There was a significant interaction (p = 0.028) between preoperative C2-T9 PA and UIV region. At a preoperative C2-T9 PA of 14° (cohort median), an upper thoracic UIV had an adjusted ARR of 36% and NNEB was 2.8. Females had an adjusted odds ratio of 1.62 (95% CI 1.03 to 2.59; p = 0.042) for PJK. CONCLUSION/UNASSIGNED:Worse preoperative sagittal malalignment, measured by C2-T9 PA, was associated with a higher risk of PJK and depended on UIV region. An upper thoracic UIV in patients with high preoperative C2-T9 PA may reduce PJK.

Resistance to Bruton's tyrosine kinase inhibitors (BTKi) remains a major therapeutic challenge in B-cell malignancies. Here, we identify chromatin remodeler BRG1-mediated suppression of ferroptosis as a central mechanism of BTKi resistance in mantle cell lymphoma (MCL), in which aberrant BRG1-dependent transcription program protects cells from BTKi-induced ferroptosis by restricting reactive oxygen species (ROS) and labile iron. Mechanistically, BRG1 promotes resistance through regulation of both BTK-dependent survival signaling and a BTK-independent transcriptional program. The latter is mediated by BRG1-driven induction of MEF2B, which upregulates atypical mitochondrial complex I subunit NDUFA4L2. Increased NDUFA4L2 restricts cellular respiration, preemptively limiting mitochondrial ROS generation and activating AMPK signaling, together reducing susceptibility to lipid peroxidation and ferroptosis. Pharmacologic inhibition of BRG1 disrupts these programs, restoring ferroptotic sensitivity and synergizing with BTKi across resistant MCL models. Together, our study establishes BRG1 as a central regulator of BTKi resistance and provides a rationale for co-targeting BRG1 and BTK as a therapeutic strategy for B-cell malignancies.

OBJECTIVE:To describe the use of peripheral nerve stimulation targeting the sacral lateral branches as a treatment for sacroiliac joint mediated low back pain refractory to conventional therapies. METHODS:A 67-year-old female with chronic sacroiliac joint (SIJ)-mediated low back pain, refractory to conservative management and sacral lateral branch radiofrequency ablation, subsequently underwent a trial and implantation of peripheral nerve stimulation (PNS) targeting the sacral lateral branches. RESULTS:The PNS trial achieved 60% pain reduction without adverse events. After permanent implantation, 12-month follow-up showed 70% sustained pain relief and ODI improvement from 68% to 28%. CONCLUSION/CONCLUSIONS:PNS of the sacral lateral branches, performed using a novel technique, appears to be a safe and effective treatment for SIJ-mediated low back pain refractory to standard therapies. Further studies are warranted to validate these findings.