Faculty Bibliography

OBJECTIVES/OBJECTIVE:Post-extubation stridor (PES) is a serious complication in pediatric patients following endotracheal intubation and is linked to laryngeal edema. Prior studies suggest that the laryngeal air column width difference (LACWD), measured by point-of-care ultrasound (POCUS), may predict PES. There is a critical need to evaluate whether such techniques can be reliably reproduced among typical providers in the pediatric critical care setting. We aimed to assess the predictive value of LACWD for PES, examine its correlation with endotracheal tube (ETT) cuff pressure, and determine whether LACWD can be measured consistently by multiple POCUS-trained providers. METHODS:We conducted a prospective observational study of 51 mechanically ventilated pediatric patients aged 0-18 years. LACWD was measured using bedside POCUS. A subset underwent duplicate scans by different providers to assess interrater reliability. PES was defined by the presence of inspiratory stridor. Intra- and interrater reliability were evaluated using intraclass correlation coefficients (ICCs). RESULTS:PES occurred in 14% of patients. There was no significant difference in LACWD between PES and non-PES groups. LACWD showed no correlation with ETT cuff pressure. Intrarater reliability for LACWD measurements was excellent (ICC >0.95), but interrater reliability was poor (ICC = 0.27 for LACWD). CONCLUSIONS:LACWD did not reliably predict PES and showed poor interrater reliability, raising concerns about its practical utility in pediatrics. While POCUS remains an appealing non-invasive tool, our study demonstrates that the current technique lacks the reproducibility required for clinical application across providers. Future advancements may improve feasibility, but current methods are not yet suitable for routine bedside use.

Introduction Cordon-based congestion policies have demonstrated air quality and health benefits in cities outside the United States (U.S.), yet selecting comparison areas to evaluate these policies remains a methodological challenge. Using two pre-policy administrative health datasets, we examined the feasibility of constructing local, state, and regional counterfactual populations to inform an evaluation of child health impacts of the recently implemented New York City (NYC) congestion pricing policy, focusing on pediatric asthma emergency department visits. Methods Our study population included children aged 0-17 years. Using a difference-in-differences approach for repeated measures, we evaluated crude pre-policy pediatric asthma trends between the congestion relief zone (CRZ) and three comparison areas: (1) NYC neighborhoods outside the CRZ, (2) nine major New York State cities, and (3) dense, heavily trafficked Northeast regional U.S. cities. We compared this approach with a generalized synthetic control method (G-SCM). Results Crude pre-policy pediatric asthma trends were most parallel between the CRZ and the local NYC comparison zone. Socioeconomic, built environment, and environmental exposure covariates varied across comparison areas at baseline. G-SCM improved visual pre-policy trend alignment across all three comparison areas; however, placebo tests revealed statistically significant parallel trend violations persisted for non-local comparison areas. Conclusions Local comparison populations may offer the most representative counterfactual for evaluating NYC congestion pricing child health impacts. Residual parallel trend violations in non-local areas underscore the methodological challenges of counterfactual selection for geographically concentrated urban policies, highlighting the value of triangulating findings across comparison areas and analytic approaches in future post-implementation evaluations.

OBJECTIVES/OBJECTIVE:Congenital high airway obstruction syndrome (CHAOS) is characterized by over-distended lungs leading to impaired cardiac return and fetal hydrops. Survivors have been reported following prenatal spontaneous fistulization, fetal procedures to decompress the airway, or ex-utero intrapartum treatment (EXIT). The long-term outcomes of survivors are unclear. METHODS:We performed a retrospective chart review on patients diagnosed with CHAOS in our center between 2005-2025. RESULTS:Of the 28 patients with CHAOS, three (10.7%) underwent a fetal procedure to decompress the airway. Three patients (10.7%) had evidence of spontaneous fistulization. Four patients (14.3%) terminated the pregnancy and four (14.3%) had in-utero fetal demise. Twenty patients (71.4%) were live-born; of these, 14 (70%) died shortly after delivery and two (10%) died in the neonatal period. Seven patients (35%) underwent EXIT-to-tracheostomy at our center, of which four (57.1%) are long-term survivors ranging in age from 4 to 19 years old. Three patients have undergone airway reconstruction between 1.6 and 5.6 years of age; one remains tracheostomy-dependent due to recurrent airway stenosis, one patient has undergone reconstruction and is likely to be decannulated soon, and one patient had successful reconstruction and was decannulated. The fourth patient has not yet undergone airway reconstruction. CONCLUSIONS:CHAOS remains a highly morbid diagnosis, but long-term survivorship and liberation from tracheostomy is possible.

INTRODUCTION/BACKGROUND:Management of relapsed mantle cell lymphoma (MCL) has included Bruton's tyrosine kinase (BTK) inhibitors for more than 10 years, but finding an optimal combination partner that meaningfully improves outcomes while limiting toxicity has been difficult. We conducted a phase 1/2 trial of ibrutinib and the proteasome inhibitor, ixazomib, in patients with relapsed/refractory MCL. PATIENTS AND METHODS/METHODS:Patients and Methods: The primary endpoint for the phase 1 study was to determine the recommended phase 2 dose (RP2D), and for the phase 2 study was the complete response (CR) rate, compared with the previously reported single-agent CR rate of ibrutinib. After the phase 1 portion of the study identified a recommended phase 2 dose of ixazomib 4 mg days 1, 8, and 15, of a 28-day cycle combined with ibrutinib 560 mg daily until progression or unacceptable toxicity. RESULTS:We enrolled 35 BTK-naïve patients to the phase 2 portion of the study. Overall response rate was 77%, and 37% of patients achieved a CR. The 2-year progression-free survival is 44%, and the duration of response is 47%. Treatment-related adverse events were common, resulting in treatment discontinuation for 37% of patients. CONCLUSION/CONCLUSIONS:Given that the progression-free survival (PFS) was not significantly improved compared to historical reports for single-agent BTK inhibitors and the high rate of treatment-related toxicity, this combination does not merit further study in this setting. Additional trials evaluating newer BTK inhibitors and alternative combination partners are warranted.

BACKGROUND:in participants with relapsed or refractory follicular lymphoma after at least one previous line of chemoimmunotherapy. METHODS:for up to 12 cycles. Epcoritamab was administered weekly in cycles 1-3 and every 4 weeks in cycles 4-12, lenalidomide once daily during cycles 1-12 (days 1-21), and rituximab weekly during cycle 1 and monthly in cycles 2-5. The dual primary endpoints were overall response rate and progression-free survival by independent review committee. The data reported here are from a planned interim analysis carried out after 78% of progression-free survival events had occurred. This study is registered with ClinicalTrials.gov, NCT05409066, and EudraCT, 2021-000169-34, and is ongoing (closed to recruitment). FINDINGS/RESULTS:(grade 1 in 28 [21%] participants and grade 2 in seven [5%] participants) and manageable, and all events were resolved. INTERPRETATION/CONCLUSIONS:as a new standard of care for second-line or subsequent treatment of follicular lymphoma. FUNDING/BACKGROUND:AbbVie and Genmab.

OBJECTIVE:Amnioinfusions in anhydramnios aim to promote fetal lung development, but currently used fluids (Normal Saline [NS], Lactated Ringer's [LR]) fail to mimic the intrauterine environment and increase reactive oxygen species (ROS). We developed a synthetic amniotic fluid (Amnio-well, AW) designed to reduce intrauterine ROS. This study evaluated the pulmonary and gastrointestinal effects of 2 formulations of AW compared with those of NS and LR in a pre-clinical model. METHOD:At gestational age E17.5, pregnant rats underwent amniotic fluid replacement with NS, LR, AW, AW plus epidermal growth factor and transforming growth factor-β (AW++), or sham control. Fetal lungs were harvested at E20.5 for histology, fractional airspace, and blinded pathological evaluation. Surfactant protein (SP-A, SP-B, SP-C) expression and inflammatory gene panels were assessed in lungs and gastrointestinal (GI) tissue. RESULTS:NS and LR lungs demonstrated edema, macrophage infiltration, and reduced airspace (p < 0.001). AW improved SP-B and SP-C relative to control, whereas AW++ suppressed SP-B and SP-C (p < 0.05). Lung gene profiling showed NS/LR induced alterations in histamines, annexins, and immune recruitment, while AW closely resembled control. GI histology was similar across groups, though NS/LR altered TNF, prostaglandin, and adhesion pathways (p < 0.05). CONCLUSION:AW reduced lung inflammation and enhanced surfactant expression compared with NS or LR, with minimal GI effects.

OBJECTIVE:To compare postnatal MRI outcomes after prenatal myelomeningocele repair using three different dural substitutes. METHOD/METHODS:32 sheep fetuses were included, with 34.3%(11/32) serving as healthy controls and the remaining undergoing prenatal spinal lumbar defect creation to recreate a myelomeningocele in the fetus. 90.5% (19/21) of sheep fetuses with surgically created MMC underwent repair using traditional collagen (Durapair) patch (n = 6), HUC matrix (NEOX RT) patch (n = 6), or a novel PLA/PCL patch (n = 7). All sheep underwent brain and spine MRI within 24 h after delivery. Images were reviewed in Research PACS by a pediatric neuroradiologist and were assessed for ventricle size, degree of hindbrain herniation, spinal cord integrity, and fluid collection at the repair site. RESULTS:There was a significant reduction in hindbrain herniation in all three intervention groups when compared with MMC without prenatal intervention. There was increased incidence of complete spinal cord defect (3/7), pseudomeningocele (5/7) and intraspinal cyst (2/7) at the repair site of the PLA/PCL patch compared with the Durapair and NEOX RT patches. CONCLUSIONS:This study demonstrates equal efficacy in reducing hindbrain herniation in MMC repair by Durapair, NEOX RT, and PLA/PCL patches by MRI. Future studies analyzing the interaction of the patches with the host tissue in animal models and clinical trials will help to better determine the true safety and efficacy of these novel patches for clinical use.

OBJECTIVE:Infants with myelomeningocele (MMC) are at risk of brainstem dysfunction secondary to symptomatic Chiari II malformation with hindbrain herniation (HH), which can manifest as feeding difficulties including aspiration and dysphagia. This study aims to investigate whether prenatal repair of MMC is associated with improved feeding outcomes compared to postnatal repair. STUDY DESIGN/METHODS:Retrospective observational study of 208 infants with MMC, 105 repaired prenatally and 103 repaired postnatally, from January 2011 to July 2022. Primary outcome was feeding tube at discharge and longitudinally through 12 months corrected gestational age (CGA). RESULTS:9.5% of infants repaired prenatally and 13.6% repaired postnatally required feeding tube at discharge (p = 0.3585). By 53 weeks CGA, the prenatal repair group had decreased odds of requiring feeding tube (0.325 [95% CI 0.121, 0.872]). CONCLUSION/CONCLUSIONS:Prenatal MMC repair was associated with decreased need for long-term feeding support, suggesting a potential functional benefit of prenatal repair related to reversal of HH.