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ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Abstract Importance Respiratory syncytial virus (RSV) hospitalization rates are highest among children <2 years of age. RSV immunization with infant monoclonal antibody or maternal vaccine is recommended to protect all U.S. infants in their first RSV season. For certain high-risk children aged 8−19 months entering their second RSV season, the monoclonal antibody nirsevimab is recommended. Little is known regarding preexisting health conditions as risk factors for RSV-associated respiratory failure in children during their second season. Objectives To describe children admitted to the pediatric intensive care unit (PICU) for RSV during their second RSV season by preexisting health conditions, and to compare demographic and clinical characteristics across groups. Design, Setting, and Participants Surveillance registry of children 8-<24 months old admitted to the PICU in 30 pediatric hospitals in the 2023-2024/2024-2025 RSV seasons. All children had an RSV-positive respiratory sample and received respiratory support with high flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation (IMV). Exposure Preexisting health conditions potentially increasing risk of severe RSV disease. Main Outcomes and Measures Patients were classified into four mutually exclusive groups by preexisting health conditions: 1) U.S. nirsevimab eligible criteria, 2) other identified RSV risk conditions (with some evidence of increased risk for severe RSV), 3) other preexisting conditions, and 4) no preexisting conditions. Patient demographic characteristics and level of respiratory support received were compared. Results Among 574 children: 47 (8.2%) had U.S. nirsevimab eligibility criteria, 76 (13.2%) had other RSV risk conditions, 96 (16.7%) had other preexisting conditions, and 355 (61.8%) had none. A higher proportion of children with nirsevimab eligibility factors (40.4%) than those with other identified RSV risk conditions (17.1%) required IMV, which was higher than other (10.4%) or no (5.9%) preexisting health conditions (p trend <0.001). Conclusions and Relevance Approximately 20% of children admitted to the PICU with severe RSV were in the defined groups that met U.S. nirsevimab-eligibility criteria or that had an identified RSV risk condition associated with known risk for severe RSV. A considerable proportion of both groups of children required IMV for respiratory support. These findings may help inform future deliberations regarding U.S. second season nirsevimab-eligibility recommendations. Key Points Question What preexisting health conditions are present in children aged 8–<24 months admitted to the pediatric intensive care unit for severe RSV disease in their second RSV season and how do clinical outcomes differ? Findings Among 574 children, 8% were eligible for nirsevimab in the U.S. and 13% had other preexisting conditions with known risk for severe RSV. Children with preexisting conditions, particularly those eligible for nirsevimab, were more likely to require invasive mechanical ventilation than those without. Meaning These findings may inform future deliberations regarding which children in their second RSV season might benefit from RSV preventive products.

e16159 Background: Pivotal trials established atezolizumab-bevacizumab and durvalumab-tremelimumab as first-line therapies for unresectable hepatocellular carcinoma (HCC). Atezolizumab plus bevacizumab demonstrated superior survival outcomes compared to sorafenib for unresectable HCC in the IMbrave150 trial in 2020, while durvalumab plus tremelimumab showed superior survival in the HIMALAYA trial in 2022. However, data on head-to-head comparison of these two combinations as first-line systemic therapy for the patient with decompensated HCC are limited. This study aims to compare survival outcomes between these two treatment regimens in decompensated HCC patients to address a critical gap in the current literature, as decompensated patients have largely been excluded from clinical trials. Methods: This retrospective study utilized electronic health records from 146 U.S. healthcare organizations within the TriNetX Network. Adults aged ≥21 years diagnosed with decompensated HCC receiving atezolizumab/bevacizumab and durvalumab/tremelimumab from 10/21/2022 to 8/20/2024 were included. The comparison group received atezolizumab/bevacizumab, and the control group received durvalumab/tremelimumab. The primary outcome was all-cause mortality. A 1:1 propensity score matching was conducted to balance baseline characteristics (age, gender, race/ethnicity, lab results including liver function tests, platelet counts, INR, gamma glutamyl transferase, alpha-fetoprotein, and underlying liver diseases). Kaplan–Meier survival analysis and Cox regression was used to estimate the mortality risk. Subgroup analysis was stratified by HCC etiology. Results: A total of 302 and 664 patients received durvalumab/tremelimumab, atezolizumab/bevacizumab, respectively. After propensity matching, 253 patients per group were included. Median OS was 283 days with durvalumab/tremelimumab and 391 days with atezolizumab/bevacizumab. The two treatment regimens showed no significant difference in survival (hazard ratio [HR]: 0.875, 95% confidence intervals [CI] 0.696–1.101, p=0.254). Subgroup analyses demonstrated no significant differences in survival between the two groups of patients in MASLD (HR: 0.698, 95% CI: 0.468–1.040), alcohol associated liver disease (HR: 0.821, 95% CI: 0.603–1.118), and chronic viral hepatitis (HR: 0.852, 95% CI: 0.596–1.219). Conclusions: There was no statistically significant difference in survival outcomes between atezolizumab plus bevacizumab and durvalumab plus tremelimumab in patients with decompensated advanced HCC. These results support current real-world practice in which both regimens may be considered viable first-line treatment options in this high-risk population with liver decompensation.

e12749 Background: Breast cancer (BC) survivors are at higher risk for recurrence or new primary disease and often require complex surveillance imaging. Use of contrast enhanced surveillance imaging modalities with contrast-enhanced digital mammography (CEM) and magnetic resonance imaging (MRI) has increased in recent years. This study evaluates characteristics of those BC survivors who receive contrast enhanced imaging and whether the addition of contrast enhanced imaging affects biopsy outcomes in BC survivors. Methods: An IRB-approved retrospective chart review identified female BC survivors who underwent breast surgery and subsequent surveillance imaging at a single academic center between 2016 and 2025. Surveillance episodes were categorized as mammography alone versus mammography with addition of CEM and/or MRI. Multivariable generalized estimating equations were used to compare patient and tumor characteristics associated with enhanced imaging modality use. Similarly rates of biopsy and cancer were evaluated with enhanced imaging use. Results: A total of 4,050 surveillance imaging episodes in 861 patients were identified and 54 resulted in biopsy-proven malignancy. Mammography alone was performed in 3,459 episodes, while enhanced imaging with CEM or MRI was used in 591 (14.6%) episodes. Use of CEM or MRI for surveillance imaging increased over time. In 2016, surveillance imaging consisted predominantly of mammography alone (93.3%) with 6.6% incorporating MRI or CEM. By 2025, mammography only surveillance decreased to 78.4% while use of MRI or CEM increased to 21.6%. Use of contrast enhanced imaging was associated with higher incidence rate ratios (IRR) for dense breast tissue [IRR 2.33; 95% CI 1.92, 2.82), p < 0.001] and less frequently used among patients aged 65–79 years [IRR 0.60, 95% CI 0.49, 0.74; p < 0.0001] and > = 80 years of age [IRR 0.40; 95% CI 0.24, 0.66; p < 0.001]. Ductal carcinoma in situ (DCIS) (IRR 3.09, p = 0.0061), and immunotherapy use (IRR 2.56, p = 0.0006) also were associated with increased use of CEM/MRI enhanced imaging. Biopsies were performed in 146 (4.2%) mammography alone episodes and 55 (9.3%) enhanced imaging episodes [IRR 2.20; 95% CI 1.63, 2.96; p < 0.001]. Surveillance with mammography yielded malignant biopsy results in 39 (1.1%) episodes, compared with 15 (2.5%) episodes using enhanced imaging [IRR 2.25; 95% CI 1.25, 4.06; p = 0.007). Conclusions: In breast cancer surveillance at our institution, the addition of contrast enhanced imaging modalities were utilized in a minority of surveillance episodes but did increase over time and were higher in patients with dense breasts. CEM or MRI usage demonstrated higher biopsy rates and increased malignancy detection compared with mammography alone, but the incidence of a positive biopsy was low. These findings suggest and are in keeping with 2023 ACR guidelines that enhanced imaging may improve cancer detection in select breast cancer survivors.

639 Background: Large cohort studies have shown a survival benefit with the use of GLP1 receptor agonists (GLP1 RA) in cancer patients. The impact of GLP1 RA usage in breast cancer (BC) and the different subtypes is unknown. To investigate the potential influence of GLP1 RA usage on BC survival, a study was conducted on a large institutional database. Methods: A de-identified institutional database identified newly diagnosed Stage I, II, and III BC patients from 2005 to present and use of GLP1 RA. The study compared survival rates for BC patients with and without GLP1 RA and further stratified by BC subtype [ER+HER2-, HER2+, ER-PR-HER2-(triple negative BC (TNBC))], BMI, and age. Kaplan-Meier survival curves were used to estimate overall survival. This study analyzed de-identified data accessed through Mayo Clinic Platform Discover. Per 45 CFR 46.102, this activity did not require IRB review. Data was extracted using an established privacy-preserving protocol and de-identified via expert determination under the HIPAA Privacy Rule. Raw EHR data and other unreported data cannot be shared due to de-identification parameters. Results: 88015 BC patients were identified, of which 3919 (4.5%) received GLP1 RA. The 5-year survival rate was 98.5% with vs 85.5% without GLP1 RA (p-value <0.0001). The survival benefit persisted for different BMI’s and ages: BMI >30 (98.4% vs 85.1%), >25 (98.4% vs 85.4%), and age <50 (99.5% vs 89.3%) and >50 (98.1% vs 84.8%) [all p<0.0001]. 21770 patients with ER+ disease were identified, of which 1412 (6.5%) received GLP1 RA. The 5-year survival rate was 99.0% vs 87.7% (p-value <0.0001). The survival benefit persisted by BMI and age: BMI >30 (99.0% vs 86.2%), >25 (98.9% vs 87.1%) and age <50 (99.6% vs 90.5%) and >50 (98.7% vs 87.2%) [all p<0.0001]. 3599 patients with HER2+ disease were identified, of which 202 (5.6%) received GLP1 RA. The 5-year survival rate was 99.3% vs 80.1% (p-value <0.0001). The survival benefit persisted by stratification: BMI >30 (100.0% vs 80.0%, p-value <0.0004), and <25 (97.7% vs 76.2%, p-value <0.019), and age <50 (100% vs 87.0%, p-value <0.043) and > 50 (99.0% vs 77.2%, p-value <0.0002). 8389 patients with TNBC disease were identified, of which 360 (4.3%) received GLP1 RA. The 5-year survival rate was 91.0% vs 71.9% (p-value <0.0001). The survival benefit persisted by stratification: BMI >30 (96.4% vs 72.9%, p-value <0.0001), >25 (93.2% vs 71.8%, p-value <0.0001), and age <50 (96.0% vs 73.0%, p-value <0.0028) and >50 (88.9% vs 71.8%, p-value <0.0001). For those TNBC patients who received GLP1 RA, having a BMI >30 conferred a protective effect with a 5-year survival rate was 97.9 vs 89.8% (p-value <0.0014). Conclusions: The study suggests that GLP1-RA improves 5-year survival rates of patients with BC and this applies to all subtypes of BC. These results suggest that further study of the impact of GLP1-RA on BC patients is warranted.

1056 Background: Resistance to HER2-directed therapies remains a major challenge in HER2-positiveMBC. In preclinical models, HER2+ tumors overexpress poly (ADP-ribose) polymerase (PARP), and PARP inhibition induces apoptosis through NF-κB suppression even in the absence of pathogenic mutations in BRCA 1/2 . We evaluated the safety, efficacy, and translational correlates of niraparib combined with trastuzumab in patients (pts) with refractory HER2+ MBC. Methods: This open-label Phase 1b/2 trial (NCT03368729) enrolled pts with HER2+ MBC (IHC 3+ and/or FISH amplified), measurable disease, LVEF ≥50%, and progression on ≥1 prior HER2-targeted therapy; stable CNS disease was allowed. Pts with germline BRCA1/2 mutations or prior PARP inhibitor exposure were excluded. Niraparib 300 mg orally was administered on Days 1–21 of a 21-day cycle with trastuzumab 6 mg/kg IV every 3 weeks (loading dose 8 mg/kg on cycle 1). The Phase 2 portion used a Gehan/Simon two-stage design with early stopping for futility (P0=24%); ≥1 response among the first 20 patients triggered expansion to 40 patients. ORR was assessed by RECIST v1.1, meeting the primary endpoint and allowing response rate estimation with <7% standard error and a two-sided 95% exact CI width of 0.28. Gene expression profiling of paired tumor tissue and peripheral blood mononuclear cells (PBMCs) was performed using the NanoString nCounter Tumor Signaling 360 panel at pretreatment compared to cycle 2. Results: Forty-six pts were enrolled (9/2019–2/2025); 41 were evaluable for response. Pts were heavily pretreated (median 3 prior regimens), including trastuzumab deruxtecan in 22 pts; 33% had brain metastases. Treatment-related adverse events were predominantly grade 1–2 and manageable. Clinical benefit rate (CBR) was 44% (18/41) including 1 complete response, 2 partial responses, and 15 stable disease. Eleven patients achieved disease control ≥ 6 months; 1 patient remained on treatment at data cutoff. Tumor profiling revealed enrichment of a B-cell–driven tertiary lymphoid structure signature with reduced hypoxia signaling in responders. Matched PBMC analyses demonstrated coordinated downregulation of interferon signaling, DNA damage response, metabolic activation, angiogenesis, and resistance pathways in clinical responders, whereas non-responders retained signatures of chronic stress and immune exhaustion. Conclusions: Niraparib plus trastuzumab demonstrated a favorable safety profile and durable clinical benefit in heavily pretreated HER2+ MBC. Integrated tumor and blood-based analyses identify immune-organized tumor microenvironments and systemic immune normalization as key correlates of prolonged response, supporting further investigation of PARP inhibition strategies. Clinical trial information: NCT03368729 .

OBJECTIVES We aimed to characterize the frequency of major complications of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) and adolescents present at 6 months after initial presentation. METHODS The Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) study was a prospective cohort at 20 US pediatric academic medical centers. Individuals aged younger than 21 years meeting any of the following were enrolled: SARS-CoV-2 detection within 7 days, Centers for Disease Control and Prevention (CDC) MIS-C criteria, or CDC MIS-C criteria except having involvement of 1 organ system. The study was designed to assess the proportion of children with major complications (cardiovascular, pulmonary, gastrointestinal/hepatic, renal, and/or neurologic) 6 months after presentation. RESULTS Data were analyzed on 229 hospitalized participants: 59 with COVID-19 (mean age 10.4 years; SD, 5.5) and 170 with MIS-C (mean age 10.1 years; SD, 4.8). Overall, 42.8% were female, making up 55.9% and 38.2% of the COVID-19 and MIS-C groups, respectively. Overall, the frequencies of major complications at 6 months after initial presentation were: 16/195 (8.2%) cardiovascular, 11/154 (7.1%) pulmonary, 11/154 (7.1%) gastrointestinal/hepatic, 3/152 (2.0%) renal, and 3/189 (1.6%) neurologic. Organ system complications did not differ significantly between the COVID-19 and MIS-C groups. Six of 14 (42.9%) COVID-19 and 21/26 (80.7%) MIS-C participants with at least 1 six-month complication had no underlying medical condition that may have been associated with their complication(s). CONCLUSIONS Major complications were infrequent but observed in children without underlying medical conditions, underscoring the importance of prospective follow-up to optimize management and elucidate the complications associated with severe SARS-CoV-2 infection in children.

Abstract Introduction Ultrasonic vaping devices like SURGE are marketed as safer alternatives to conventional coil-based electronic cigarettes like JUUL due to their lower operating temperatures. However, their impact on cardiovascular health has not been fully characterized. Methods Sprague–Dawley rats were exposed daily for 9 weeks to aerosol generated from SURGE, JUUL, or clean air. Heart rate variability was continuously monitored via implanted telemetry. Cardiac fibrosis was quantified using histological analysis. Temperature profiles of SURGE, JUUL, and Nautilus (a coil-based tank device) were recorded. Aerosol samples were analyzed for carbonyl compounds using high-performance liquid chromatography. Results Both SURGE and JUUL exposures significantly reduced heart rate variability (high frequency and total power) compared with air. JUUL exposure significantly increased cardiac fibrosis; SURGE showed a similar mean fibrosis level but greater variability, resulting in a non-significant difference. SURGE devices operated at lower peak temperatures (~131°C) than JUUL (~239°C) and Nautilus (~160–170°C). Despite having the lowest temperature, SURGE emitted higher levels of carbonyl compounds than JUUL, although still substantially lower than Nautilus. Conclusions Although SURGE operates without coils and at lower temperatures than coiled vaping devices, it generates higher levels of carbonyls than some coiled devices and impairs cardiac autonomic regulation, and it can cause cardiac fibrosis comparable with JUUL although with high variability; that is, SURGE does not reliably avoid the increase in fibrosis caused by conventional electronic cigarettes. These findings suggest that non-thermal mechanisms predominate in mediating cardiovascular toxicity associated with ultrasonic vaping, challenging the assumption that coil-free designs are inherently safer. Implications Despite its lower operating temperature and coil-free design, the SURGE ultrasonic vaping device impaired cardiac autonomic function and promoted fibrosis at a mean level comparable to that of JUUL. These findings challenge claims of reduced harm from coil-less vaping technologies and suggest that non-thermal mechanisms may drive toxicity. Regulatory evaluations should consider device emissions and physiological outcomes—not just hardware features. Physicians and policymakers should be aware that coil-less systems may still pose cardiovascular risks, and marketing these devices as inherently safer may mislead users and undermine tobacco harm reduction efforts.

Abstract Background and aims Systemic inflammation has been implicated in cognitive decline and dementia pathogenesis. Interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cardiovascular disease, may play a role in cerebrovascular and neurodegenerative processes. We examined the relationship between IL-6 levels and incident dementia risk using the Atherosclerosis Risk In Communities (ARIC) study. Methods ARIC study participants at Visit 4 (1996-1998) had IL-6 measurements and were followed for incident dementia over 25 years. IL-6 levels were dichotomized at the median value of 1.5 pg/mL. Incident dementia cases were identified through standardized surveillance. Cox proportional hazards regression calculated hazard ratios (HR) with 95% confidence intervals (CI), adjusting for age, race, gender, hypertension, diabetes, obesity, physical activity, smoking, alcohol use, education, income, insurance status, and ApoE-ε4 allele status. Results Participants (n=5,662; mean age 62.4±5.6 years, 55% female, 83% White, 17% Black) were followed for a median of 25 years. Those with IL-6 &gt;1.5 pg/mL demonstrated significantly increased dementia risk versus IL-6 ≤1.5 pg/mL. The crude HR was 1.23 (95% CI 1.11-1.37). After adjustment, the association remained significant with HR 1.13 (95% CI 1.01-1.27). Kaplan-Meier survival curves showed progressive divergence between groups, with lower dementia-free survival in the higher IL-6 group, log-rank p&lt;0.001. Conclusions Elevated mid-life IL-6 levels (&gt;1.5 pg/mL) independently predict increased long-term dementia risk over 25 years, even after adjusting for cardiovascular and sociodemographic confounders. These findings support systemic inflammation's role in dementia pathogenesis and highlight IL-6 as a potential biomarker for dementia risk. Conflict of interest Karly Pikel, Natasha Carmichael, Alana E. Barton, Kevin Moss, Christine Downey, Ryan T. Demmer, Pamela L. Lutsey, Souvik Sen: Nothing to disclose Figure 1 - belongs to Conclusions

Study Design. Subanalysis of a prospective, multicenter, observational study at 72 US adult, pediatric, and mixed trauma centers. Objective. We investigated trauma-related risk factors and patient-level factors associated with multiregional spinal column injury, defined as cervical spine injury (CSI) requiring treatment and thoracolumbar injury (TLI). Summary of Background Data. Traumatic spinal injury causes morbidity and mortality in pediatric patients. Injuries to multiple spinal column regions require early identification and thoughtful management. Methods. All children <18 years undergoing cervical spine evaluation after blunt multisystem trauma were prospectively identified and enrolled. Clinically significant CSI was defined by cervical spine surgery or halo placement. TLI incidence and management was recorded. The primary outcome was multiregional spinal column injury (CSI+TLI). Results. Of 19,651 enrolled patients, 1484 children (7.5%) experienced a TLI, 159 (0.81%) had CSI requiring treatment, and 30 (0.15%) had CSI+TLI. Multivariate analysis revealed that the trauma-related factors mechanism of injury ( P <0.001), rib fractures (odds ratio (OR) 2.8 [2.3-3.4]), hemothorax/pneumothorax (OR 2.0 [1.7-2.4]), bowel injury (OR 4.0 [2.9-5.4]), pelvic fracture (OR 1.5 [1.2-1.9]), and clinically significant CSI (OR 1.9 [1.2-2.9]) were independently associated with TLI. Of the 159 children with clinically significant CSI, 30 also experienced TLI (19%). Multivariate analysis identified prehospitalization intubation (OR 3.1 [1.1-8.4]) and rib fractures (OR 3.9 [1.2-12.8]) as independent associations with CSI+TLI. Conclusions. Of children with CSI requiring treatment, 19% experienced TLI. MOI and various trauma-related injuries were independently associated with TLI, whereas prehospitalization intubation and rib fractures were independent risk factors for CSI+TLI. These factors should trigger screening for multiregional spinal column injury in pediatric trauma patients. Furthermore, if there is known TLI, the cervical spine should be evaluated, and if there is significant CSI, then dedicated imaging of the thoracic and lumbar spine is indicated. Level of Evidence. III