Citations

Abstract Background Inadvertent temporary transvenous pacing (TTVP) of left ventricle (LV) is rare and likely underreported, posing significant embolic risk. We present a case of TTVP with atypical trajectory identified on computed tomography (CT) imaging. Summary A 62-year-old male with metastatic renal cell carcinoma on chemotherapy and bifascicular block presented with symptomatic bradycardia and non–ST-elevation myocardial infarction (NSTEMI), raising concerns for complete heart block on ECG. Intermittent asystole occurred during TTVP placement with appropriate capture. Post-procedure, ECG showed ventricular-paced rhythm with pseudo-right bundle branch block, and chest X-ray suggested lead placement in right ventricle; however, suboptimal echocardiography limited lead visualization. Coronary angiography revealed non-obstructive coronary artery disease. Positron emission tomography–computed tomography (PET-CT), performed to evaluate immune checkpoint inhibitor myocarditis, incidentally noted TTVP wire entering right subclavian artery and traversing to LV. Patient underwent TTVP removal, endovascular repair, and pacemaker implantation; however, course was unfortunately complicated by embolic stroke and haemorrhagic conversion. Discussion Early detection and management of lead malposition remain critical to minimizing complications. Management strategies for inadvertent lead malposition (ILM) depend on duration of implantation, clinical presentation, and associated risks. This case highlights importance of recognizing this high-risk complication, preventive strategies, and evidence-based management. While existing data primarily focus on ILM in permanent devices, further research is needed to elucidate incidence, predictors, and outcomes of ILM in TTVP, particularly in resource-limited settings.

Pediatric metabolic dysfunction–associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a lack of accurate non-invasive tests and effective pharmacotherapy, both stemming from a paucity of multicenter clinical trials in pediatric MASLD. We provide clear steps to address this public health emergency by promoting awareness campaigns, educating and empowering patients and families, addressing barriers including access to care, nutritional and exercise support programs, establishing multidisciplinary care, launching community initiatives, and conducting clinical trials in pediatric MASLD for an age-based evaluation of novel diagnostic and therapeutic options. We conclude by highlighting the urgent need for comprehensive public health policies to control the tide of pediatric MASLD and call upon stakeholders to act now.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

ABSTRACT Background The Society of Pediatric Liver Transplantation (SPLIT) has undergone tremendous growth with > 45 sites contributing data focusing on improving outcomes in pediatric liver transplantation (LT). We report and compare outcomes from the SPLIT Registry. Methods Patients < 18 years with first‐time LT only enrolled into the SPLIT Registry between 2011 and 2023 were included. Data was stratified into eras from the last published registry update (era 1: 2011–2018, era 2: 2018–2023). Results Three thousand five hundred four participants from 47 centers were included (era 1: n = 2159; era 2: n = 1345). Age distribution differed with more children < 1 year. of age at LT in era 2 (era 1: 29% vs. era 2: 33%, p = 0.01). Indications for LT were similar, with biliary atresia (38.8%) and metabolic disease (16.0%) being most common. Exception point use was higher in era 2 (era 1: 45% vs. era 2: 56%, p < 0.001). No difference in graft type (deceased: 81% era 1 vs. 78% era 2, p = 0.78), patient survival at 90 days (era 1: 98.7% vs. era 2: 98.3%), 1 year (era 1: 97.2 vs. era 2: 96.8%), or 3 years (era 1: 95.3% vs. era 2: 95.2%) was noted. Rate of hepatic artery thrombosis was lower in era 2 (era 1: 7% vs. era 2: 5%, p = 0.02). Conclusions Trends in pediatric LT within SPLIT note similar LT indications and graft type, higher utilization of exception points, and lower HAT rates despite transplanting more children < 10 kg. This data underscores the evolution of pediatric LT toward higher survivability and overall patient outcomes.

Recent guidelines on biliary cannulation are lacking. This guideline is an initiative of the World Endoscopy Organization (WEO) with the involvement of a panel of experts from Asia, Europe, and America. Relevant clinical questions on four areas (post‐endoscopic retrograde cholangiopancreatography [ERCP] pancreatitis [PEP] prophylaxis, biliary cannulation techniques, sphincterotomy/papillary balloon dilation, and biliary cannulation in special circumstances) were developed and answered after systematic reviews of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Successful biliary cannulation and sphincterotomy are cornerstones of ERCP and are indispensable for almost all therapeutic and advanced diagnostic procedures. However, adverse events, particularly PEP, may commonly occur and impair patients' outcomes. A high cannulation rate and a low rate of PEP are quality indicators for ERCP and should be the goal of all endoscopists. With this guideline we aimed to provide clinical practice advice applicable worldwide, regardless of resources and expertise availability. The main recommendations focus on specific aspects of ERCP, including pre‐, intra‐, and postprocedural measures to reduce the risk of PEP, the technique for an initial biliary cannulation attempt, options for cannulation in cases of difficult biliary access, alternatives to ERCP in case of failure (percutaneous‐ and endoscopic ultrasound‐guided), and biliary access in altered anatomy (periampullary diverticulum and postsurgical anatomy) and in the presence of duodenal stenosis.

ABSTRACT Background Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) are primarily used to manage type 2 diabetes mellitus (T2DM) and heart failure (HF), but their impact on reducing stroke risk in patients with atrial fibrillation (AF) remains underexplored. We aimed to investigate the impact of SGLT2‐Is for stroke risk mitigation in patients with AF. Methods Using the TriNetX database, we performed a retrospective cohort study on patients ≥ 18 years with AF and on anticoagulation. These patients were then classified into two cohorts based on their use of SGLT2‐Is. To balance the baseline demographics, comorbidities, and medication use, propensity score matching (PSM) was used. The primary outcome was ischemic and hemorrhagic strokes, and the secondary outcomes were all‐cause mortality, all‐cause hospitalizations, need for AF cardioversion or antiarrhythmic drug initiation, and cardiac arrest. Adjusted odds ratio (aORs) and hazard ratios (HRs) were estimated for both the primary and secondary outcomes. Results A total of 152,778 patients with 76,389 patients were included in each cohort (SGLT2‐Is users, and non‐users) after PSM. The mean age of both SGLT2‐Is users and non‐users was 72.8 years. For the SGLT2‐Is users, the mean follow‐up period was 317 days, whereas the mean follow‐up period for the non‐users was 306 days. For the primary outcome, we found that SGLT2‐Is users had a lower risk of ischemic stroke (aOR: 0.889; 95% CI: 0.857–0.923) and hemorrhagic stroke (aOR: 0.682; 95% CI: 0.620–0.749) compared to non‐users. Regarding the secondary outcomes, SGLT2‐Is users also had lower risk for all‐cause mortality (aOR: 0.615; 95% CI: 0.595–0.636), all‐cause hospitalizations (aOR: 0.599; 95% CI: 0.587–0.611), need of AF cardioversion (aOR: 0.846; 95% CI: 0.813–0.881), antiarrhythmic drug initiation (aOR: 0.790; 95% CI: 0.766–0.815), and cardiac arrest (aOR: 0.643; 95% CI: 0.601–0.688). Conclusions SGLT2‐I use in patients with AF is associated with lower risks of stroke and other cardiovascular and non‐cardiovascular outcomes. Future prospective research is needed to validate these findings.

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV longitudinal strain (RVLS) in clinical practice. RVLS provides a more sensitive indicator of subtle myocardial dysfunction than conventional parameters for RV function assessment (i.e., tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction), with utility for the risk stratification and surveillance of conditions affecting the right heart. However, accurate interpretation of RVLS requires a comprehensive understanding of RV mechanics, pathology, and loading conditions across various cardiovascular conditions, as well as the effects of image quality and technical aspects of image acquisition and tracking in RV strain measurements. This review provides an updated overview of current practical guidelines for RV strain analysis, current clinical applications, and future directions for its potential use in clinical practice.

TPS3644 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera™, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines v serial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 1-27-2025): 647/1,912. NCT: 05174169. Support: U10 CA180868, -180822; -180888; UG1 CA189867; Natera, Inc. Clinical trial information: NCT05174169 .

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06