Citations

Abstract Topic Benign Disease: Gastro-Esophageal Reflux and Hiatal Hernia Background Ambulatory reflux monitoring (wireless pH or catheter-based pH-impedance) performed off acid suppression is the gold standard for diagnosing gastroesophageal reflux disease (GERD). Barium esophagram (BE), commonly used to evaluate esophageal symptoms, routinely assesses reflux, yet its diagnostic accuracy relative to ambulatory monitoring remains unclear. Existing studies are limited, relied on outdated reflux criteria, and demonstrated poor concordance with BE-based GERD diagnoses. We aimed to determine whether BE reliably identifies GERD compared with ambulatory reflux monitoring interpreted using updated Lyon 2.0 consensus criteria. Methods Retrospective analysis of adult patients that underwent BE and ambulatory reflux monitoring (wireless pH or pH-impedance) off PPI within an 8-month interval. Patients with a history of fundoplication were excluded. Esophagram was performed with standard technique and reported by radiology, considered positive for GERD if there was reflux above the thoracic inlet with or without provocative maneuvers. Reflux monitoring studies were considered positive or negative for GERD based on Lyon consensus 2.0 recommendations. Inter-rater reliability, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and received operating characteristic (ROC) curve analysis were calculated for esophagram, with reflux monitoring diagnosis as the gold standard. Results 64 patients were included, 31 % male, mean age = 60 years, mean Body Mass Index = 26. GERD was diagnosed by esophagram in 20 patients (31%), and by reflux monitoring in 19 (30%). Compared to reflux monitoring, BE had sensitivity: 47%, specificity: 76%, PPV: 45%, NPV: 77%, and area under the ROC curve: 0.61 (Figure 1). Inter-rater reliability between BE and ambulatory reflux monitoring was poor (Cohen's Kappa = 0.226). Conclusion There was poor concordance between BE and ambulatory reflux monitoring for diagnosing GERD. BE overall had suboptimal diagnostic performance, with low sensitivity, and moderate specificity. Furthermore, the area under the ROC curve indicates limited ability to distinguish correctly between patients with and without GERD. These findings indicate that barium esophagram should not be relied upon as a diagnostic tool for GERD.

Abstract Topic Benign Disease: Gastro-Esophageal Reflux and Hiatal Hernia Background Ambulatory reflux monitoring off acid suppression is the gold standard for diagnosing gastroesophageal reflux disease (GERD). Barium esophagram (BE) routinely evaluates reflux, but its diagnostic accuracy remains uncertain. We assessed whether BE reliably identifies GERD compared with ambulatory reflux monitoring interpreted using updated Lyon 2.0 consensus criteria. Methods Retrospective analysis of adult patients that underwent BE and ambulatory reflux monitoring (wireless pH or pH-impedance) off PPI within an 8-month interval. Patients with a history of fundoplication were excluded. Esophagram was performed with standard technique and reported by radiology, considered positive for GERD if there was reflux above the thoracic inlet with or without provocative maneuvers. Reflux monitoring studies were considered positive or negative for GERD based on Lyon consensus 2.0 recommendations. Inter-rater reliability, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and received operating characteristic (ROC) curve analysis were calculated for esophagram, with reflux monitoring diagnosis as the gold standard. Results 64 patients were included, 31 % male, mean age = 60 years, mean Body Mass Index = 26. GERD was diagnosed by esophagram in 20 patients (31%), and by reflux monitoring in 19 (30%). Compared to reflux monitoring, BE had sensitivity: 47%, specificity: 76%, PPV: 45%, NPV: 77%, and area under the ROC curve: 0.61 (Figure 1). Inter-rater reliability between BE and ambulatory reflux monitoring was poor (Cohen's Kappa = 0.226). Conclusion There was poor concordance between BE and ambulatory reflux monitoring for diagnosing GERD. BE overall had suboptimal diagnostic performance, with low sensitivity, and moderate specificity. Furthermore, the area under the ROC curve indicates limited ability to distinguish correctly between patients with and without GERD. These findings indicate that barium esophagram should not be relied upon as a diagnostic tool for GERD.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of large B-cell lymphoma (LBCL) with around 90% of patients cured with frontline treatment. For relapsed or refractory (R/R) disease, the optimal treatment is unclear. CD19 chimeric antigen receptor-T cell (CAR-T) has been established as the preferred second line (2L) treatment for primary refractory or early relapsing LBCL based on the overall survival benefits observed in the landmark phase III trials. However, PMBCL patients were underrepresented on these pivotal studies. This study evaluated outcomes of 252 patients treated with 2L therapies for R/R PMBCL at 14 US institutions between 2001 and 2025. Platinum-based salvage with intent to proceed to high dose therapy and autologous stem cell transplant (HDT/ASCT) (platinum cohort) and CD19 CAR-T (CAR-T cohort) were given as 2L therapy in the real-world setting in 157 and 26 patients, respectively. Overall response rate (ORR), complete response (CR) rate and median progression-free survival (PFS) were significantly higher in the CAR-T cohort compared with the platinum cohort (ORR: 91.3% vs 44.2%, p <0.001; CR 65.2% vs 14.7%, p<0.001; median PFS not reached vs 3.5 months, hazard ratio (HR) 0.28, 95% CI 0.15-0.54, p=0.001). No significant difference was observed in overall survival. This study demonstrated superior response rate and PFS of CD19 CAR-T over platinum-based salvage with intent to proceed to HDT/ASCT as 2L treatment for R/R PMBCL.

Background Advanced chronic kidney disease (CKD) complicates anticoagulant treatment because thromboembolic and bleeding risks compete. We compared treatment outcomes for apixaban and rivaroxaban in adults with atrial fibrillation (AF) and stage 4/5 CKD. Methods Deidentified TriNetX records for patients treated with apixaban (n=49,698) and rivaroxaban (n=2660) underwent 1:1 propensity score matching (demographics, medications, procedures, laboratory values); 2533 matched pairs were identified (absolute standardized mean difference <0.10, indicating adequate balance). The smaller rivaroxaban cohort constrained matching; findings apply only to the matched population. Outcomes were assessed at 1, 3, and 5 years. Myocardial infarction (MI) findings were exploratory. P values were not adjusted for multiplicity. Results Gastrointestinal bleeding was lower for apixaban vs rivaroxaban (5-year: 9.3% vs 10.9%; relative risk [RR], 0.86; 95% CI, 0.71-1.02; P=.09). Cerebrovascular events were significantly higher for apixaban vs rivaroxaban at 3 years only (9.8% vs 7.9%; RR, 1.24; 95% CI, 1.01-1.53; P=.04); this association may reflect chance. Cerebral infarction was significantly higher for apixaban vs rivaroxaban at 1 year (3.0% vs 1.8%; RR, 1.61; 95% CI, 1.09-2.37; P=.02) and attenuated at 3 and 5 years. Rates of MI were nominally higher in the apixaban group. Five-year mortality risk was significantly lower for apixaban vs rivaroxaban (33.3% vs 36.1%; RR, 0.92; 95% CI, 0.86-0.10; P=.04) but differences in time-to-event survival were not significant. Conclusion Apixaban did not have greater bleeding risk than rivaroxaban and may be associated with lower gastrointestinal bleeding, a finding that requires further study. Isolated cerebrovascular, MI, and mortality findings require cautious interpretation. A mortality advantage for either drug was not established.

Abstract. Introduction: Preterm birth drives adverse perinatal maternal and infant health outcomes through heterogeneous symptoms, severity, and etiologies. Delivery prior to reaching 37 weeks of gestation may result from medically indicated intervention for pregnancy complications or spontaneously in the absence of prior symptoms. Placental tissue collected following preterm birth exhibits differential DNA methylation compared to full-term placentas and may indicate pregnancy health during gestation. Placental DNA currently has limited utility for assessing health of ongoing pregnancy, as sampling placental tissue during gestation increases the risk of infection and miscarriage. Risks associated with placental sampling during pregnancy limit the use of DNA methylation in clinical preterm birth prediction. Assessing preterm birth risk during gestation requires non-invasive methods for characterizing placental DNA methylation. Results: We quantified genome-wide DNA methylation patterns of hypermethylated cell-free DNA in pregnant (n = 99) and non-pregnant (n = 93) plasma using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq). In each sample, we assessed DNA methylation status in 300-bp genomic windows, examining both sequencing read counts and calculated absolute molar DNA amount. Known hypermethylated placental regions, including RASSF1, STAT5A, and ERG promoters showed significantly increased odds of detection in pregnant samples, suggesting enrichment of cell-free placental DNA. Of the 536,444 300-bp windows examined, 173,071 (32%) showed significant enrichment in pregnant plasma. Linear modeling identified 107,505 differentially methylated regions (DMRs) associated with pregnancies later diagnosed with intrauterine growth restriction (IUGR) (n = 22). Alu elements showed increased representation in these DMRs than expected, while other repetitive elements exhibited underrepresentation. Discussion: These results demonstrate cfMeDIP-seq's ability to enrich for cell-free placental DNA and characterize cell-free DNA methylation signatures of pregnancies complicated by IUGR. Enrichment of cell-free placental DNA enables non-invasive profiling of placental DNA methylation from maternal plasma. Detectable epigenetic signatures in maternal plasma may identify pregnancies at elevated risk for preterm birth before clinical symptoms appear. Our findings further highlight the potential of cell-free placental DNA for monitoring pregnancy health.

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

Chimeric antigen receptor (CAR) T-cell therapy is a transformative modality for refractory hematologic malignancies; however, its adoption in Latin America and the Caribbean (LAC) is severely constrained by prohibitive manufacturing costs, limited specialized infrastructure, and fragmented regulatory frameworks. To address this translational gap, we propose a pragmatic, cost-adapted model for establishing Good Manufacturing Practice (GMP) laboratories tailored to the socioeconomic realities of LAC. This model advocates for decentralized, modular cleanroom facilities that integrate fully closed automated manufacturing platforms with risk-based quality management systems. Furthermore, we emphasize the strategic implementation of artificial intelligence (AI) and digital health tools—such as electronic batch records and predictive analytics—to optimize resource utilization and ensure stringent regulatory compliance. Essential to this framework is the cultivation of a specialized local workforce and the promotion of regional regulatory harmonization through initiatives like PAHO’s Red PARF. Ultimately, this scalable approach provides a realistic roadmap to democratize CAR T-cell therapy in LAC, fostering regional biomanufacturing autonomy and promoting equitable patient access.

Abstract Objective Surgery is an effective, yet underutilized treatment for children with drug‐resistant epilepsy. Although predictors of surgical outcomes are well described, the decision to recommend surgery varies by institution. We aim to evaluate the rates of not recommending surgery, identify associated patient characteristics, and quantify variability across centers. Methods We queried the Pediatric Epilepsy Research Consortium Surgery database, a prospective multicenter cohort of children (0–18 years) undergoing initial evaluation for epilepsy surgery. Patients with documented surgical decisions were included. Demographic, clinical, and presurgical evaluation variables were compared by surgical recommendation status. Logistic regression identified factors associated with not recommending surgery. Mixed‐effects models quantified between‐center variability. Results Among 2480 patients across 29 centers, 532 (21%) were not recommended epilepsy surgery (median center rate 17%, interquartile range [IQR] 10%–28%). After accounting for patient characteristics associated with surgical candidacy, substantial variation in decision‐making remained across centers, with a median twofold difference in the odds of not recommending surgery between otherwise similar patients evaluated at different institutions (Median Odds Ratio = 2.25; Intraclass Correlation Coefficient = .18). The clinical characteristics most strongly associated with not recommending surgery included monthly or less frequent seizures (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.75–2.69), non‐structural etiology (OR 2.02, 95% CI 1.56–2.61), and taking ≤2 anti‐seizure medications (ASMs) (OR 1.67, 95% CI 1.34–2.08, all p 's < .01). These characteristics showed minimal clustering across centers (ICCs < .05). Significance One in five children evaluated for epilepsy surgery are not recommended to pursue surgical treatment. Although clinical factors influence decision‐making, they do not explain the substantial variation in recommendations across pediatric epilepsy centers. Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision‐making contributes importantly to surgical candidacy.

ABSTRACT We report the case of a 38‐year‐old recreational female runner with anterior and lateral chronic exertional compartment syndrome treated with ultrasound‐guided fasciotomy using a V‐shaped meniscotome. She began her return‐to‐run protocol 8 days postprocedure and achieved full symptom resolution. At 6 months, ultrasound revealed persistent fascial separation without complications, representing the first report of long‐term sonographic outcomes following fasciotomy for chronic exertional compartment syndrome. These findings support further prospective studies to evaluate the clinical and sonographic outcomes of this technique.