Citations

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 INTRODUCTION Plasma p‐tau217 and p‐tau217/Aβ42 reliably identify non‐Hispanic White individuals with symptomatic and pre‐clinical AD. However, performance across ethnoracially diverse groups remains unknown. METHODS Cognitively normal Black, Hispanic, and non‐Hispanic White participants completed cognitive evaluations, brain magnetic resonance imaging (MRI), amyloid and tau positron emission tomography (PET), and measures of kidney function. Plasma p‐tau217 and Aβ42 were measured using Fujirebio Lumipulse assays. Pre‐clinical AD detection was evaluated using symptomatic and cohort‐derived optimized cutoffs. RESULTS Among 191 participants (57 Black, 46 Hispanic White, 88 non‐Hispanic White), age‐adjusted plasma p‐tau217 and p‐tau217/Aβ42 performed similarly in detecting amyloid‐positive individuals (≥ 25 Centiloids), regardless of race/ethnicity. Both measures independently correlated with amyloid deposition, whereas estimated glomerular filtration rate (eGFR) correlated solely with p‐tau217. Pre‐clinical AD optimized cutoffs (p‐tau217 ≥ 0.132 pg/ml; p‐tau217/Aβ42 ≥ 0.0059) outperformed cutoffs established in symptomatic individuals (sensitivity: 83% vs. 57%; 77% vs. 63%; negative predictive value [NPV] > 93%). DISCUSSION Plasma biomarkers performed similarly across ethnoracially diverse cohorts. Optimized cutoffs may improve early detection and trial enrollment.

Obesity is common among critically ill adults, but its association with outcomes during venovenous extracorporeal membrane oxygenation (VV ECMO) remains controversial. We evaluated associations of body mass index (BMI) with mortality and Extracorporeal Life Support Organization (ELSO)–defined complications in adults supported with VV ECMO. We conducted a retrospective multicenter cohort study of adults receiving VV ECMO at four centers (2017–2025). The primary outcome was in-hospital mortality; secondary outcomes were ELSO-defined complications. Multivariable logistic regression was adjusted for age, sex, and hospital site; BMI was evaluated as continuous, dichotomized (≥30 vs . <30 kg/m 2 ), and World Health Organization (WHO) obesity class exposures, with interaction testing by coronavirus disease 2019 (COVID-19) status. Among 420 patients (median BMI, 31 kg/m 2 ), in-hospital mortality was 62%. Higher BMI was associated with mortality in non–COVID-19 acute respiratory distress syndrome (ARDS; odds ratio [OR] = 1.06 per 1 kg/m 2 , 95% confidence interval [CI] = 1.02–1.10, p = 0.003) but not in COVID-19 ARDS (OR = 1.00, 95% CI = 0.94–1.05); there was insufficient evidence of interaction between BMI and COVID-19 ( p = 0.07). Higher BMI was associated with renal complications in both groups and infectious complications in non–COVID-19 ARDS (OR = 1.05, 95% CI = 1.02–1.09, p = 0.003). No significant BMI × COVID-19 interaction was detected for any outcomes. These findings do not support an obesity survival paradox during VV ECMO.

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

Abstract Introduction Fetal growth restriction (FGR) is associated with an increased risk of neonatal morbidity and mortality. Current diagnostic criteria for FGR do not discriminate between constitutionally small and pathologically restricted fetuses. Following FGR diagnosis, umbilical artery (UA) Doppler is utilized to monitor fetal well‐being, but its limitations have increased interest in investigating growth velocity as an adjunctive tool. The objective of this study is to compare the predictive ability of UA Doppler studies and growth velocity for adverse neonatal outcomes in growth‐restricted fetuses. Methods This is a secondary analysis of a cohort of pregnancies delivered in a single healthcare network from August 2017 to December 2022, diagnosed antenatally with FGR. The cohort was restricted to those with baseline estimated fetal weight (EFW) between the 3rd and 50th percentiles. All subjects had growth velocity measured (defined as EFW percentile change per week between baseline and subsequent ultrasound). The primary outcome was a composite of neonatal morbidity (neonatal intensive care unit [NICU] admission, low 5‐min Appearance, Pulse, Grimace, Activity, Respiration score [<7], intraventricular hemorrhage, necrotizing enterocolitis, or metabolic acidosis) and severe adverse perinatal events (stillbirth or neonatal death, hypoxic ischemic encephalopathy, mechanical ventilation, or severe metabolic acidosis [pH < 7.0]). Neonatal morbidity and severe adverse perinatal events were analyzed separately as secondary outcomes. Independence between growth velocity and S/D ratio was evaluated. Univariate logistic regression models were then performed, with each outcome of interest as the dependent variable and S/D ratio and growth velocity as independent variables. Receiver operating characteristic (ROC) curves were generated to compare the performance of both tests. Results A total of 172 patients were included in the analysis. UA Doppler data were available for 165 patients, 15.3% of whom had S/D ratio >95th percentile; none demonstrated absent or reversed end‐diastolic flow. There was no correlation observed between S/D ratio percentile and growth velocity, suggesting independence. ROC analysis demonstrated that the discriminatory ability of growth velocity was higher across outcomes with areas under the curve (AUC) ranging from 0.65 to 0.69 while AUC for S/D ratio percentiles ranged from 0.51 to 0.53, approximating the performance of chance. Higher growth velocity was significantly associated with reduced odds of the composite outcome (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.69–0.90), and neonatal morbidity (OR, 0.84; 95% CI, 0.73–0.95). S/D ratio percentile was not associated with these outcomes. Conclusion In pregnancies complicated by growth restriction with forward UA flow, growth velocity outperformed S/D ratio percentile in predicting adverse outcomes. The two tests were independent, indicating that growth velocity may reflect a component of fetal development not captured by UA Doppler. These results suggest that growth velocity could be used in addition to UA Doppler studies for fetal risk assessment, especially in fetuses with forward arterial flow.

Lay Summary Glioblastoma is an aggressive brain cancer, and it can be difficult to tell whether changes seen on scans after radiation treatment represent tumor growth or treatment-related effects. The authors of this study wanted to evaluate whether a specialized imaging test called PSMA PET could help define tumor boundaries for radiation planning and distinguish tumor progression from treatment-related changes. To do this, they performed PSMA PET scans in 27 patients with high-grade gliomas, including patients undergoing radiation planning and patients being evaluated for possible tumor recurrence. They found that tumors showed higher PSMA PET signal than surrounding tissue, that PSMA PET sometimes identified tumor beyond what was visible on standard MRI, and that it correctly distinguished tumor progression from treatment-related changes in most patients.

Purpose of review Artificial intelligence applied to electrocardiography (AI-ECG) has rapidly been investigated in adult cardiovascular medicine, yet translation into pediatric and congenital heart disease populations has lagged. This review summarizes contemporary AI-ECG methodologies and emerging applications in pediatric and congenital heart disease (PCHD), with emphasis on current clinical utility, technical challenges, and future opportunities for implementation. Recent findings Recent studies demonstrate that deep learning models can accurately identify arrhythmias, ventricular dysfunction, and CHD from standard ECG. Convolutional neural networks remain the dominant architecture, although transformer-based foundation models and self-supervised learning approaches are increasingly being explored. AI-ECG applications in PCHD have expanded from automated interpretation toward proactive risk stratification, including prediction of ventricular dysfunction, mortality, and sudden cardiac death risk. Additional work has investigated wearable monitoring, telemetry analysis, and integration with longitudinal clinical data. Despite promising performance, most studies remain retrospective and single-center, with limited external validation and challenges related to small datasets, physiologic heterogeneity, and age-dependent ECG variation. Summary AI-ECG has the potential to transform PCHD by improving diagnostic accuracy, enabling earlier disease detection, and enhancing longitudinal risk assessment. Broader clinical implementation will require multicenter collaboration, prospective validation, standardized datasets, and careful attention to ethical, regulatory, and equity considerations.

ABSTRACT Consumer‐grade wearables, including smartwatches, fitness trackers, and smart rings, are accessible tools for studying pharmacologic responses in real‐time, monitoring participant health in decentralized clinical trials, optimizing outcome measures, and delivering digital interventions that promote behavior change. However, incorporating consumer wearables into clinical studies is not as straightforward as simply purchasing devices and providing them to participants. It requires engaging with a complex engineering ecosystem with multiple investigator decisions on device selection, associated data management practices, and patient/participant engagement and technical support. This tutorial, based on experience running large clinical trials using consumer wearables, outlines the wearables market landscape across varying form factors and manufacturers as well as the data management software products supporting wearable use. It delineates the major decision processes involved in designing studies that incorporate wearables and presents a structured framework to guide the selection of devices and supporting data tools according to study objectives.

OBJECTIVE Cognard type V dural arteriovenous fistulas (dAVFs), defined by spinal perimedullary venous drainage, represent a rare and aggressive neurovascular pathology. Comprehensive multicenter data remain scarce. The authors present the largest multicenter analysis to date, characterizing presentation, radiology, treatment, complications, and functional outcomes of Cognard type V dAVFs. METHODS The authors retrospectively analyzed patients with angiographically confirmed Cognard type V dAVFs from the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR), spanning 16 academic centers. Patient demographics, imaging features, treatment strategies, procedural complications, and modified Rankin Scale (mRS) scores were recorded. RESULTS Among 1077 patients with dAVFs, 37 (3%) had Cognard type V lesions. The mean patient age was 57 years, and 59.5% of patients were male. Most presented with nonhemorrhagic neurological deficits (68%), while 14% had hemorrhage. The most common location was the foramen magnum (32%). Embolization was the primary treatment in 67% of cases, complete obliteration was achieved in 71% of cases. Upfront microsurgery was performed in 22% of patients (obliteration rate 88%), and radiosurgery in 14% (success rate 40%). Salvage treatment further improved obliteration outcomes. Temporary complications occurred in 8% of patients (3/37): 2 with transient neurological deficits postembolization and 1 with transient hydrocephalus after surgery. Permanent complications were observed in 3% (1/37) due to treatment-related hemorrhage. At the last follow-up (mean 2.4 years), 69% (24/35) of patients maintained or improved to an mRS score ≤ 2. No deaths occurred. Functional improvement was seen in 29% (10/35), while mRS decline was in 40% of patients (14/35), all unrelated to the dAVF itself. CONCLUSIONS Cognard type V dAVFs carry a high risk of neurological morbidity. However, favorable functional outcomes are achievable with timely, multimodal intervention. Complication rates remain low, with most being transient. These data support aggressive but tailored management to prevent permanent disability in this high-risk population.