Publications

Abstract

Introduction: Preterm birth includes four subgroups: extremely (<28 weeks’ gestation), very (28⁺⁰-31⁺⁶), moderate (32⁺⁰-33⁺⁶, MPT) and late (34⁺⁰-36⁺⁶, LPT). While school attainment is well-studied across subgroups, other aspects of daily life are rarely reported for MPT, LPT and early term (37⁺⁰-38⁺⁶, ET) or are explored only qualitatively.

Objective: Assess daily life, including school and quality of life at age 10 years for MPT, LPT and ET compared with full-term (39⁺⁰-40⁺⁶, FT) peers.

Methods: Children born in 2011 from two birth cohorts (ELFE: ≥33⁺⁰ weeks; EPIPAGE-2: ≤34⁺⁶ weeks) completed a 10-year follow-up via telephone interview (n=8373) and home visit (n=6418). Weighting addressed selection bias. Outcome-wide regressions (modified Poisson, linear) were used to calculate adjusted relative risks (aRR) and beta-coefficients (β).

Results: MPT had a higher risk of receiving any school support (aRR 1.67, 95% CI 1.10 to 2.54). Their risk for difficulties in French and mathematics was, respectively, 1.32 (95% CI 1.01 to 1.74) and 1.50 (95% CI 1.13 to 1.99) times higher, while school-related quality of life was 0.30 (95% CI -0.58 to -0.02) SD lower relative to FT. They were 2.02 times more likely to be non-swimmers (95% CI 1.24 to 3.29). Both MPT/LPT were less likely to eat school meals but reported higher overall well-being scores (+0.16 SD and +0.13 SD, respectively). The study sample may under-represent socioeconomically deprived groups.

Conclusions: MPT/LPT children’s daily lives differ from those of FT children in some respects. Those discrepancies should be explored further to better understand needs and accommodate them. Findings may not generalise to disadvantaged groups.

Keywords: Child Development; Epidemiology; Follow-Up Studies.

Abstract

Four-dimensional ultrafast ultrasound imaging is emerging as a major paradigm shift in biomedical imaging by enabling the direct visualization and quantification of dynamic physiological processes in three-dimensional space over time. This review provides a comprehensive overview of the principles, technological developments, and applications that underpin this rapidly evolving field. We first describe the foundations of volumetric ultrafast acquisition based on unfocused wave transmissions and coherent compounding, followed by key advances in volumetric beamforming, motion estimation, Doppler imaging, elastography, and ultrasound localization microscopy. Particular emphasis is placed on the hardware challenges associated with matrix array transducers, including channel count limitations, data throughput, and emerging solutions such as microbeamforming, sparse arrays, row-column addressing, and wearable probes. We further highlight the critical role of high-performance computing and artificial intelligence in enabling real-time processing and analysis of large volumetric datasets. Beyond acquisition and reconstruction, this review underscores the importance of advanced visualization and quantification strategies as essential tools for extracting meaningful information from complex 4D data. Applications ranging from in vitro validation to preclinical and early clinical studies in cardiovascular, neurovascular, and abdominal imaging demonstrate the unique capabilities of this modality. Finally, we discuss current limitations and future directions, emphasizing the need for scalable hardware, efficient data handling, and new conceptual frameworks to fully exploit the spatiotemporal richness of 4D ultrafast ultrasound.

No abstract available

Abstract

Background: Racial inequities in maternal morbidity and mortality persist in the postpartum period. Postpartum hospital use (PHU), including readmissions and emergency department visits, occurs in 5% to 9% of births, with rates among Black individuals at the higher end of this range. Risk-targeted interventions may improve efficiency and equity by directing resources to those at greatest risk postpartum and addressing structural barriers to care. Building on prior prediction model development and community-engaged intervention design, we conducted a pilot randomized controlled trial using a validated PHU risk calculator to identify and enroll high-risk participants into a postpartum education and patient navigation intervention.

Objective: To evaluate feasibility and engagement with a postpartum educational and patient navigation intervention and generate preliminary estimates of effectiveness in reducing PHU within 30 days of delivery discharge.

Study design: We conducted a randomized controlled trial among Black individuals who gave birth at a Philadelphia academic medical center between February 2024 and April 2025. Recruitment was guided by a risk calculator derived from a previously validated prediction model for PHU. Study coordinators abstracted predictor data from medical charts; self-identified Black individuals with ≥5.5% predicted PHU were eligible (cut-point selected from validation). Participants were enrolled before discharge from delivery hospitalization and randomized 1:1 to receive a postpartum educational and patient navigation intervention or standard care. The intervention included bedside printed and electronic education materials, and patient navigation including an in-hospital educational session and support via text message and phone calls through 30 days postpartum. The primary outcome was hospital use within 30 days of discharge, ascertained via electronic medical record and self-report. Secondary outcomes included depressive symptoms, self-efficacy, and perceived access to care self-reported on surveys at 3 weeks postpartum. Feasibility measures, including recruitment yield, retention, and implementation challenges identified from study logs and research team debriefs.

Results: Among 1051 individuals screened, 616 (58.6%) were eligible and approached for enrollment, and 220 were enrolled and randomized (110 intervention, 110 control). Use of the risk calculator resulted in a high social vulnerability cohort: 50.0% with annual household income <$45,000 and 14.2% unhoused. Clinical risk scores were similar in intervention and control groups. Coordinators reported challenges to risk calculator use, including time-intensive abstraction, discrepancies between variable definitions in administrative data (model development) and medical records (recruitment), and missing data. The overall 30-day cumulative incidence of PHU was 18.2%. Incidence was 20.0% among intervention participants and 16.4% among control participants (risk ratio [95% confidence interval]=1.2 [0.7-2.0]). Secondary outcomes were similar between groups. Among intervention participants, 79% reported that the educational materials were helpful and 61% reviewed them more than once.

Conclusion: Among Black participants at elevated risk, engagement with a postpartum patient navigation and education intervention was high, although preliminary estimates did not suggest reduced PHU. Risk-based recruitment identified a cohort with elevated PHU but posed challenges for real-time risk ascertainment. These findings can inform larger multisite trials of risk-targeted, multilevel postpartum interventions.

Keywords: disparities; intervention; maternal health; navigation; postpartum.

Abstract

We conducted a retrospective analysis of data collected prospectively from a cohort of 114 neonates with hypoxic-ischemic encephalopathy. Magnetic resonance imaging (MRI) obtained during therapeutic hypothermia showed 95% concordance with MRI obtained at a median postnatal age of 11 days in regard to injury pattern and severity. These results support MRIs during therapeutic hypothermia as a reliable tool to assess brain injury, facilitating timely clinical decisions, parental counseling, and trial enrollment.

Keywords: birth asphyxia; hypoxic-ischemic encephalopathy; magnetic resonance imaging; therapeutic hypothermia.

Abstract

Conventional dendritic cells (cDCs) are key sentinels at epithelial barriers, regulating immunity to microbial pathogens and commensals while preserving tissue integrity. NOTCH2 deficiency in CD11c-expressing cells (Notch2^cKO) disrupts type 2a DC (cDC2a) development, impairs intestinal T_H17 immunity and increases susceptibility to enteropathogenic bacteria. This defect leads to persistent dysbiosis in Notch2^cKO mice, characterized by low-grade inflammation and systemic autoimmune features, including elevated autoantibody titers and renal immune complex deposition. Dysbiosis precedes expansion of highly inflammatory AXL-expressing type 3 DCs (AXL⁺inf-DC3), promoting chronic inflammation and tertiary lymphoid structures driving adaptive immune responses. Notably, dysbiosis is defined by three dominant pathobionts and is transferable to wild-type mice, recapitulating the autoimmune features observed in Notch2^cKO mice. Here these findings identify a microbiota-DC axis linking intestinal pathobionts to systemic autoimmunity, establishing inflammatory DC3 as the cellular bridge between dysbiosis, chronic inflammation and autoimmune pathogenesis.

Abstract

Neonatal dysbiosis of the gut microbiota represents a critical environmental factor promoting obesity, but the underlying immunological mechanisms remain unknown. We show here that neonatal treatment of mice with broad-spectrum antibiotics for the first 3 weeks of life (NeoATB) resulted in the development of obesity and metabolic abnormalities in adulthood. The NeoATB mice exhibited a permanent dysbiosis of gut microbiota, decreased CD4⁺Foxp3⁺ regulatory T cells (Tregs), and increased proinflammatory Th1 cells in visceral adipose tissue (VAT). Mechanistically, neonatal antibiotic treatment resulted in increased intestinal permeability that allowed bacterial translocation into the VAT and liver and an increase in systemic LPS levels. Consequently, VAT CD11c⁺MHCII⁺ cells were activated via the TLR4 pathway to increase IL-12-triggered Th1-inflammation. Moreover, the decrease in VAT Tregs in NeoATB mice was attributed to reduced infiltration of Tregs from the periphery, decreased expansion of adipose IL-33-mediated ST2⁺ Tregs, and reduced conversion of local Tregs from VAT CD4⁺CD25^– Foxp3^– T cells. Thus, we have revealed a previously unrecognized immunological link between neonatal microbiota dysbiosis and the development of obesity.

Keywords: ST2; TGFβ signaling; Treg; inflammation; intestinal permeability; microbiota dysbiosis; neonatal age; obesity.

Abstract

Background: Antimicrobial exposure is nearly universal among very preterm infants, yet evidence to guide optimal treatment duration and sepsis management remains limited. Unnecessary prolonged antimicrobial use may contribute to adverse outcomes and antimicrobial resistance. We aimed to characterize international practices in the management of culture-proven infections in infants born <29 weeks’ gestation.

Methods: This cross-sectional study surveyed neonatal intensive care units (NICUs) across 12 networks within the International Network for Evaluating Outcomes of Neonates. A pre-piloted online questionnaire captured unit-level practices regarding treatment duration for culture-proven infections, antifungal prophylaxis, blood culture collection, and central line management. Responses were analyzed descriptively at the network and unit levels.

Results: Of 608 eligible NICUs, 382 (62.8%) responded. A 7-day treatment duration was most commonly reported for gram-positive sepsis (45.2% of NICUs), whereas 14 days was most commonly reported for gram-negative sepsis (44.4%). Treatment durations were longer for concurrent meningitis: 57% of units reported 14 days for gram-positive meningitis and 69.2% reported 21 days for gram-negative meningitis. Antifungal prophylaxis was reported by 62.1% of units. Most NICUs (79.7%) routinely obtained blood cultures from a single sterile site. Overall, 75.7% of units reported central line removal for gram-negative sepsis and 57.3% for gram-positive sepsis.

Conclusions: Reported antimicrobial duration and sepsis management practices for very preterm infants varied across neonatal units and international networks. These findings underscore persistent uncertainty and the urgent need for high-quality evidence to inform standardized, evidence-based antimicrobial stewardship in this vulnerable population.

Abstract

Objectives: To assess the technical performance of a rapid direct-from-blood antibiotic susceptibility test (AST) using MIC test strips (MTS-AST) directly on enterobacteria-positive blood culture broth.

Methods: Fifty contrived blood culture bottles (BACT/ALERT FA plus) were prepared using 10 mL of sheep blood and a diluted bacterial suspension. A collection of 50 enterobacterial isolates was used, including 25 strains previously recovered from blood cultures and 25 additional strains exhibiting various mechanisms of resistance. Blood culture bottles were incubated in the BACT/ALERT VIRTUO system until they flagged positive. Then they were pulled and two drops of blood culture broth (approximately 100 µL) were directly poured and streaked onto a Mueller-Hinton agar plate. MIC test strips were immediately laid on the plate, before incubation at 35°C ± 1°C in an aerobic atmosphere for 5 h. Seven β-lactams were tested including amoxicillin, amoxicillin/clavulanate, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime and meropenem. Comparator MICs were obtained using MIC test strips according to the manufacturer’s instructions with a standardized inoculum and 24 h of incubation. Essential agreement (EA), categorical agreement (CA) and bias were determined.

Results: EA and CA between the MTS-AST and the comparator method were ≥94% and ≥90%, respectively, with no very major error. Positive bias was apparent for all antibiotics.

Conclusions: MTS-AST provided rapid results (in 5 h) that correlated well with the comparator method on blood culture broth containing Enterobacterales. Given the shorter time to results, the reduced time cost, the limited handwork and the reduced cost per test, the MTS-AST constitutes a fast and reliable method

Abstract

Aim: The number of pregnancies among women with cystic fibrosis (wwCF) has steadily increased over the past decade. However, the pharmacokinetics (PK) of elexacaftor-tezacaftor-ivacaftor (ETI) during gestation remains uncharacterized, despite its widespread use in this population. To date, no clinical trials have investigated the effectiveness, safety or PK profiles of ETI during pregnancy. Given the significant physiological changes that occur throughout gestation, which can alter drug PK, characterizing how pregnancy impacts ETI exposure represents a key step towards informing appropriate dosing strategies. Therefore, the aim of this analysis was to assess pregnancy effect on ETI PK.

Method: As part of the French national observational cohort study, therapeutic drug monitoring was performed in 145 wwCF, including 14 pregnant participants. PK profiles for each compound were characterized using the previously published ETI adult population PK model from the same cohort, with model development and evaluation performed using Monolix® software.

Results: A total of 294 plasma samples, including 47 collected from pregnant participants, were drawn during routine clinical care. Pregnancy was found to significantly increase the apparent clearance of tezacaftor (0.97 to 1.44 L/h) and of ivacaftor (9.64 to 11.36 L/h), indicating a decrease in systemic exposure.

Conclusion: These findings raise important questions regarding whether decreased total tezacaftor and ivacaftor exposure may compromise the sustained treatment efficacy. The necessity for dose adjustments during pregnancy remains to be evaluated from a PK (unbound ETI concentrations) and pharmacodynamic (clinical effectiveness) perspective, thus warranting further studies.

Keywords: cystic fibrosis; elexacaftor–tezacaftor–ivacaftor; population pharmacokinetics; pregnancy.