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Background: To address reimbursement challenges associated with long-acting reversible contraception (LARC) in the postpartum period, state Medicaid programs have provided additional payments ("carve-outs"). Implementation has been heterogeneous, with states providing separate payments for the device only, procedure only, or both the device and procedure. Methods: Claims data were drawn from 210,994 deliveries in the United States between 2012 and 2018. Using generalized estimating equations, we assess the relationship between Medicaid carve-out policies and the likelihood of LARC placement at (1) 3 days postpartum, (2) 60 days postpartum, and (3) 1 year postpartum, in Medicaid and commercially insured populations. Results: Among Medicaid beneficiaries, the likelihood of receiving LARC was higher in states with any carve-out, compared with states without carve-outs, at 3 days (adjusted odds ratio [aOR] 1.49 [95% confidence interval: 1.33-1.67], p < 0.001), 60 days (aOR: 1.40 [95% CI: 1.35-1.46], p < 0.001), and 1 year postpartum (aOR: 1.15 [95% CI: 1.11-1.20], p < 0.001). Adjustments were made for geographic region, seasonality, and patient age. Heterogeneity was observed by carve-out type; device carve-outs were consistently associated with greater likelihood of postpartum LARC placement, compared with states with no carve-outs. Similar trends were observed among commercially insured patients. Conclusion: Findings support the effectiveness of Medicaid carve-outs on postpartum LARC provision, particularly for device carve-outs, which were associated with increased postpartum LARC placement at 3 days, 60 days, and 1 year postpartum. This outcome suggests that policies to address cost-related barriers associated with LARC devices may prove most useful in overcoming barriers to immediate postpartum LARC placement, with the overarching aim of promoting reproductive autonomy.

This study aims to develop a semiautomated pipeline and user interface (LiVaS) for rapid segmentation and labeling of MRI liver vasculature and evaluate its time efficiency and accuracy against manual reference standard. Retrospective feasibility pilot study. Liver MR images from different scanners from 36 patients were included, and 4/36 patients were randomly selected for manual segmentation as referenced standard. The liver was segmented in each contrast phase and masks registered to the pre-contrast segmentation. Voxel-wise signal trajectories were clustered using the k-means algorithm. Voxel clusters that best segment the liver vessels were selected and labeled by three independent radiologists and a research scientist using LiVaS. Segmentation times were compared using a paired-sample t-test on log-transformed data. The agreement was analyzed qualitatively and quantitatively using DSC for hepatic and portal vein segmentations. The mean segmentation time among four readers was significantly shorter than manual (3.6 ± 1.4 vs. 70.0 ± 29.2 min; p < 0.001), even when using a higher number of clusters to enhance accuracy. The DSC for portal and hepatic veins reached up to 0.69 and 0.70, respectively. LiVaS segmentations were overall of good quality, with variations in performance related to the presence/severity of liver disease, acquisition timing, and image quality. Our semi-automated pipeline was robust to different MRI vendors in producing segmentation and labeling of liver vasculature in agreement with expert manual annotations, with significantly higher time efficiency. LiVaS could facilitate the creation of large, annotated datasets for training and validation of neural networks for automated MRI liver vascularity segmentation. HIGHLIGHTS: Key Finding: In this pilot feasibility study, our semiautomated pipeline for segmentation of liver vascularity (LiVaS) on MR images produced segmentations with simultaneous labeling of portal and hepatic veins in good agreement with the manual reference standard but at significantly shorter times (mean LiVaS 3.6 ± 1.4 vs. mean manual 70.0 ± 29.2 min; p < 0.001). Importance: LiVaS was robust in producing liver MRI vascular segmentations across images from different scanners in agreement with expert manual annotations, with significant ly higher time efficiency, and therefore potential scalability., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

In this study, the authors measured and described the costs of coordinated specialty care (CSC) for first-episode psychosis in Ohio. A microcosting tool was used to estimate personnel and nonpersonnel costs of service delivery at seven CSC programs. Average annual cost per participant (N=511 participants) was estimated as $17,810 (95% CI=$9,141-$26,479). On average, 61% (95% CI=53%-69%) of annual program costs were nonbillable. Key cost drivers included facility costs, administrative tasks, and social services. Novel financing models may redress reimbursement gaps incurred by CSC programs., Competing Interests: Dr. Wastler reports receiving funding from the American Foundation for Suicide Prevention. Dr. Breitborde serves as an external consultant to Arizona Complete Health. The other authors report no financial relationships with commercial interests.

Background: Acid reflux index (ARI) is a biomarker for gastroesophageal reflux disease (GERD). The effects of short-term proton pump inhibitor (PPI) therapy on pharyngoesophageal motility and clearance mechanisms in infants remain unknown. We hypothesized that pharyngoesophageal reflexes and response to PPI are distinct between infants with 3%-7% and >7% ARI., Methods: Secondary analysis was performed from a subset of infants who participated in a randomized controlled trial (NCT: 02486263). Infants (N = 36, 29.9 ± 4.3 weeks gestation) underwent 4 weeks of PPI therapy, 1 week of washout, and longitudinal testing to assess: (a) clinical outcomes; (b) pH-impedance and symptom metrics including ARI, distal baseline impedance, clearance time, refluxate height, symptoms, I-GERQ-R scores, symptom association probability; (c) pharyngoesophageal motility reflexes and sensory motor characteristics. Comparisons were performed between infants with 3%-7% versus >7% ARI., Key Results: From the 36 hospitalized infants treated: Pharyngoesophageal reflex latencies were prolonged (p > 0.05) and duration in ARI 3%-7% group only (p = 0.01); GER frequency, proximal ascent and clearance increased (ARI 3%-7%); weight gain velocity, oral feeding success, and fine motor score decreased while length of hospital stays increased in the ARI >7% group despite the decrease in symptoms and I-GERQ-R scores., Conclusions & Inferences: Distinct changes in pharyngoesophageal sensory motor aspects of motility and reflex mechanisms exist after using PPI therapy in infants. Contributory factors may include the effects of maturation and aerodigestive comorbidities (GERD and BPD). Controlled studies incorporating placebo are needed to delineate the effects of PPI on causal and adaptive GERD mechanisms in infants with aerodigestive and feeding-related comorbidities., (© 2023 John Wiley & Sons Ltd.)

Background: Shifts in the US drug supply, including the proliferation of synthetic opioids and emergence of xylazine, have contributed to the worsening toll of the overdose epidemic. Drug checking services offer a critical intervention to promote agency among people who use drugs (PWUD) to reduce overdose risk. Current drug checking methods can be enhanced to contribute to supply-level monitoring in the USA, overcoming the selection bias associated with existing supply monitoring efforts and informing public health interventions., Methods: As a group of analytical chemists, public health researchers, evaluators, and harm reductionists, we used a semi-structured guide to facilitate discussion of four different approaches for syringe service programs (SSPs) to offer drug checking services for supply-level monitoring. Using thematic analysis, we identified four key principles that SSPs should consider when implementing drug checking programs., Results: A number of analytical methods exist for drug checking to contribute to supply-level monitoring. While there is likely not a one-size-fits-all approach, SSPs should prioritize methods that can (1) provide immediate utility to PWUD, (2) integrate seamlessly into existing workflows, (3) balance individual- and population-level data needs, and (4) attend to legal concerns for implementation and dissemination., Conclusions: Enhancing drug checking methods for supply-level monitoring has the potential to detect emerging threats in the drug supply and reduce the toll of the worsening overdose epidemic., (© 2024. The Author(s).)

Over the past decade, significant investments have been made in coordinated specialty care (CSC) models for first episode psychosis (FEP), with the goal of promoting recovery and preventing disability. CSC programs have proliferated as a result, but financing challenges imperil their growth and sustainability. In this commentary, the authors discuss (1) entrenched and emergent challenges in behavioral health policy of consequence for CSC financing; (2) implementation realities in the home rule context of Ohio, where significant variability exists across counties; and (3) recommendations to improve both care quality and access for individuals with FEP. The authors aim to provoke careful thought about policy interventions to bridge science-to-service gaps, and in this way, advance behavioral health equity., (© 2023. National Council for Mental Wellbeing.)

This study evaluates trends in long-acting reversible contraception (LARC) services among obstetrician/gynecologists (OB/GYNs) and non-OB/GYNs in the U.S. during 2012-2018. Using public and private insurance claims from the Symphony Health database, we calculated the percentage of LARC insertions, removals, and reinsertions performed by OB/GYNs and non-OB/GYNs. We then assessed time trends with linear regression. The proportion of LARC services that were performed by non-OBGYNs increased modestly between 2012 and 2018. Increases were similar for insertions, removals, and reinsertions. Further research is needed to understand trends in LARC service provision within primary care to better tailor medical training and policy interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Significant heterogeneity exists among people who use drugs (PWUD). We identify distinct profiles of syringe service program (SSP) clients to (a) evaluate differential risk factors across subgroups and (b) inform harm reduction programming., Methods: Latent class analysis (LCA) was applied to identify subgroups of participants (N = 3418) in a SSP in Columbus, Ohio, from 2019 to 2021. Demographics (age, sex, race/ethnicity, sexual orientation, housing status) and drug use characteristics (substance[s] used, syringe gauge, needle length, using alone, mixing drugs, sharing supplies, reducing use, self-reported perceptions on the impact of use, and treatment/support resources) were used as indicators to define latent classes. A five-class LCA model was developed, and logistic regression was then employed to compare risk factors at program initiation and at follow-up visits between latent classes., Results: Five latent classes were identified: (1) heterosexual males using opioids/stimulants with housing instability and limited resources for treatment/support (16.1%), (2) heterosexual individuals using opioids with stable housing and resources for treatment/support (33.1%), (3) individuals using methamphetamine (12.4%), (4) young white individuals using opioids/methamphetamine (20.5%), and (5) females using opioids/cocaine (17.9%). Class 2 served as the reference group for logistic regression models, and at the time of entry, class 1 was more likely to report history of substance use treatment, overdose, HCV, sharing supplies, and mixing drugs, with persistently higher odds of sharing supplies and mixing drugs at follow-up. Class 3 was more likely to report history of overdose, sharing supplies, and mixing drugs, but outcomes at follow-up were comparable. Class 4 was the least likely to report history of overdose, HCV, and mixing drugs, but the most likely to report HIV. Class 5 was more likely to report history of substance use treatment, overdose, HCV, sharing supplies, and mixing drugs at entry, and higher reports of accessing substance use treatment and testing positive for HCV persisted at follow-up., Conclusions: Considerable heterogeneity exists among PWUD, leading to differential risk factors that may persist throughout engagement in harm reduction services. LCA can identify distinct profiles of PWUD accessing services to tailor interventions that address risks, improve outcomes, and mitigate disparities., (© 2023. The Author(s).)

Background: Eating difficulties are common in high-risk neonatal intensive care unit (NICU) infants; mechanisms remain unclear. Crib-side pharyngo-esophageal motility testing is utilized to assess contiguous swallowing physiology, and cross-system interplay with cardio-respiratory rhythms. Aims were to: (1) identify whether distinct pharyngeal rhythms exist during oral milk challenge (OMC), and (2) develop a chronic tube feeding risk prediction model in high-risk infants., Methods: Symptomatic NICU infants (N = 56, 29.7 ± 3.7 weeks birth gestation) underwent pharyngo-esophageal manometry with OMC at 40.9 ± 2.5 weeks postmenstrual age (PMA). Exploratory cluster data analysis (partitioning around k-medoids) was performed to identify patient groups using pharyngeal contractile rhythm data (solitary swallows and swallows within bursts). Subsequently, (a) pharyngeal-esophageal, cardio-respiratory, and eating method characteristics were compared among patient groups using linear mixed models, and (b) chronic tube feeding prediction model was created using linear regression., Results: Three distinct patient groups were identified with validity score of 0.6, and termed sparse (high frequency of solitary swallows), intermediate, or robust (high swallow rate within bursts). Robust group infants had: lesser pharyngeal and esophageal variability, greater deglutition apnea, pharyngeal activity, and esophageal activity (all p < 0.05), but less frequent heart rate decreases (p < 0.05) with improved clinical outcomes (milk transfer rate, p < 0.001, and independent oral feeding at discharge, p < 0.03). Chronic tube feeding risk = -11.37 + (0.22 × PMA) + (-0.73 × bronchopulmonary dysplasia) + (1.46 × intermediate group) + (2.57 × sparse group)., Conclusions: Robust pharyngeal rhythm may be an ideal neurosensorimotor biomarker of independent oral feeding. Differential maturation of cranial nerve-mediated excitatory and inhibitory components involving foregut, airway, and cardiac rhythms distinguishes the physiologic and pathophysiologic basis of swallowing and cardio-respiratory adaptation., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

BACKGROUND. Histologic fibrosis stage is the most important prognostic factor in chronic liver disease. MR elastography (MRE) is the most accurate noninvasive method for detecting and staging liver fibrosis. Although accurate, manual ROI-based MRE analysis is complex, time-consuming, requires specialized readers, and is prone to methodologic variability and suboptimal interreader agreement. OBJECTIVE. The purpose of this study was to develop an automated convolutional neural network (CNN)-based method for liver MRE analysis, evaluate its agreement with manual ROI-based analysis, and assess its performance for classifying dichotomized fibrosis stages using histology as the reference standard. METHODS. In this retrospective cross-sectional study, 675 participants who underwent MRE using different MRI systems and field strengths at 28 imaging sites from five multicenter international clinical trials of nonalcoholic steatohepatitis were included for algorithm development and internal testing of agreement between automated CNN-based and manual ROI-based analyses. Eighty-one patients (52 women, 29 men; mean age, 54 years) who underwent MRE using a single 3-T system and liver biopsy for clinical purposes at a single institution were included for external testing of agreement between the two analysis methods and assessment of fibrosis stage discriminative performance. Agreement was evaluated using intraclass correlation coefficients (ICCs). Bootstrapping was used to compute 95% CIs. Discriminative performance of each method for dichotomized histologic fibrosis stage was evaluated by AUC and compared using bootstrapping. RESULTS. Mean CNN- and manual ROI-based stiffness measurements ranged from 3.21 to 3.34 kPa in trial participants and from 3.21 to 3.30 kPa in clinical patients. ICC for CNN- and manual ROI-based measurements was 0.98 (95% CI, 0.97-0.98) in trial participants and 0.99 (95% CI, 0.98-0.99) in clinical patients. AUCs for classification of dichotomized fibrosis stage ranged from 0.89 to 0.93 for CNN-based analysis and 0.87 to 0.93 for manual ROI-based analysis ( p = .23-.75). CONCLUSION. Stiffness measurements using the automated CNN-based method agreed strongly with manual ROI-based analysis across MRI systems and field strengths, with excellent discriminative performance for histology-determined dichotomized fibrosis stages in external testing. CLINICAL IMPACT. Given the high incidence of chronic liver disease worldwide, it is important that noninvasive tools to assess fibrosis are applied reliably across different settings. CNN-based analysis is feasible and may reduce reliance on expert image analysts.

Esophageal distal baseline impedance (DBI) is an indicator of mucosal integrity; lower values suggest increased permeability. Aims were to characterize the (1) effect of DBI category (<900 Ω, 900-2000 Ω, and >2000 Ω) on sensory-motor characteristics of mid-esophageal provocation-induced motility reflexes, and (2) clinical outcomes among high-risk human infants evaluated for gastroesophageal reflux disease. Symptomatic infants (N = 49, 41 ± 3 weeks postmenstrual age) underwent pH-impedance testing to characterize acid reflux index (ARI) and DBI, and pharyngo-esophageal manometry to examine upper esophageal sphincter (UES), peristaltic, and lower esophageal sphincter (LES) functions. Sensory-motor response characteristics included response threshold (ml), occurrence (%), latency (s), duration (s), and magnitude (mmHg) upon mid-esophageal stimulations (0.1-2.0 ml of air, water, and apple juice). Motility and clinical outcomes were compared among DBI groups. In infants with DBI <900 Ω and 900-2000 Ω (vs. >2000 Ω): (a) Long-term feeding milestones did not differ (p > 0.05); (b) complete peristaltic propagation decreased in 900-2000 Ω (p < 0.05), polymorphic waveforms increased in <900 Ω and 900-2000 Ω (p < 0.05); (c) media effects were noted with liquids (vs. air) wherein UES and esophageal contractility were prolonged in <900 Ω and 900-2000 Ω (p < 0.05), and esophageal sensitivity heightened for <900 Ω with water and for 900-2000 Ω with air (both p < 0.05). ARI was not correlated with DBI in infants with chronic lung disease (r = 0.05, p = 0.82). We conclude that pharyngo-esophageal motility sensory-motor characteristics in infants are modified by DBI category. These preliminary findings pave-the-way for further physiological testing in convalescing high-risk infants to ascertain potential mechanisms of airway-digestive reflex interactions and symptom generation, which may lead to targeted therapies., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Infants in the neonatal intensive care unit (NICU) frequently have feeding difficulties with the root cause remaining elusive to identify. Evaluation of the provider/parent/infant feeding process may provide objective clues to sources of feeding difficulty. Specialized testing may be necessary to determine if the infant's swallowing skills are dysfunctional, immature, or maldeveloped, and to determine the risk of feeding failure or chronic tube feeding. Current evidence-based diagnostic and management approaches resulting in successful oral feeding in the NICU infant are discussed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To test the hypothesis that esophageal and sphincteric sensory-motor reflexes are distinct across maturation in infants with dysphagia receiving gastrostomy-tube (G-tube). This is a retrospective review of 29 dysphagic infants (N = 15 study requiring gastrostomy, N = 14 age matched control achieving oral feeds) that underwent longitudinal pharyngeal-esophageal manometry at 42.3 (37-50.2) weeks postmenstrual age (PMA) and 48.9 (43.3-57.9) weeks PMA. Graded stimuli (0.1-5 mL) of varying media (air, water, and apple juice) tested esophageal peristaltic reflex, upper esophageal sphincter contractile reflex (UESCR), and lower esophageal sphincter relaxation reflex (LESRR). Comparisons were performed between study and controls and across maturation (time-1 vs time-2). Data represented as mean ± SE or OR (95% CI). Across maturation (time-1 vs time-2): Study infants did not exhibit significant differences across in peristaltic, UES, or LES reflexes (all p > 0.05). In contrast, controls exhibited increased UES resting pressure (13 ± 3 vs 17 ± 3 mmHg, p = 0.001), LES resting pressure (22 ± 3 vs 25 ± 3 mmHg, p < 0.009), LES nadir pressure (0.5 ± 1 vs 4.3 ± 1 mmHg, p = 0.001), and esophago-deglutition responses [2.5 (1.23-4.88), p = 0.04], and decreased secondary peristalsis [0.44 (0.31-0.61), p = 0.001], UESCR [0.4 (0.25-0.65), p = 0.001], LESRR [0.4 (0.24-0.75), p = 0.01], and symptoms [0.6 (0.45-0.83), p = 0.005]. Among infants with dysphagia, esophageal provocation induced peristaltic reflex, UESCR, and LESRR advance with longitudinal maturation when infants are oral-fed successfully, but not in those who received gastrostomy. Underlying mechanisms may be related to esophageal sensitivity, afferent or efferent transmission, and coordination of upstream excitation and downstream inhibition, which can be potential therapeutic targets for improving feeding capabilities after gastrostomy placement in infants with dysphagia., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background and Aims: To evaluate and compare gastro-esophageal reflux (GER) symptom scores with pH-impedance and test the effects of acid-suppressive medications with or without feeding modifications on pH-impedance in high-risk infants., Methods: Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants evaluated in a tertiary care setting for GER disease. Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared., Results: (A) Correlations between I-GERQ-R and pH-impedance metrics were weak. (B) I-GERQ-R sensitivity, specificity, and positive predictive values were suboptimal when correlated with pH-impedance metrics. I-GERQ-R negative predictive value (NPV) was high for acid symptom-association probability (NPV = 84%) and distal baseline impedence (NPV = 86%) thresholds. (C) PPI with feeding modifications (vs PPI alone) did not alter pH-impedance metrics or symptom scores ( P > .05); however, bolus clearance metrics worsened for both treatment groups ( P < .05)., Conclusions: In high-risk infants (1) I-GERQ-R may be a helpful clinical screening tool to exclude acid-GER disease diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis. (2) Acid-suppressive therapy with feeding modifications has no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy, which may signal development of pharyngoesophageal dysmotility and persistence of symptoms. (3) Placebo-controlled trials are needed in high-risk infants with objective pH-impedance criteria to determine efficacy, safety, and underlying mechanisms. Clinicaltrials.gov ID: NCT02486263., Competing Interests: Conflicts of Interest: The authors disclose no conflicts.

Purpose: To develop a convolutional neural network (CNN)-based deformable lung registration algorithm to reduce computation time and assess its potential for lobar air trapping quantification., Materials and Methods: In this retrospective study, a CNN algorithm was developed to perform deformable registration of lung CT (LungReg) using data on 9118 patients from the COPDGene Study (data collected between 2007 and 2012). Loss function constraints included cross-correlation, displacement field regularization, lobar segmentation overlap, and the Jacobian determinant. LungReg was compared with a standard diffeomorphic registration (SyN) for lobar Dice overlap, percentage voxels with nonpositive Jacobian determinants, and inference runtime using paired t tests. Landmark colocalization error (LCE) across 10 patients was compared using a random effects model. Agreement between LungReg and SyN air trapping measurements was assessed using intraclass correlation coefficient. The ability of LungReg versus SyN emphysema and air trapping measurements to predict Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages was compared using area under the receiver operating characteristic curves., Results: Average performance of LungReg versus SyN showed lobar Dice overlap score of 0.91-0.97 versus 0.89-0.95, respectively ( P < .001); percentage voxels with nonpositive Jacobian determinant of 0.04 versus 0.10, respectively ( P < .001); inference run time of 0.99 second (graphics processing unit) and 2.27 seconds (central processing unit) versus 418.46 seconds (central processing unit) ( P < .001); and LCE of 7.21 mm versus 6.93 mm ( P < .001). LungReg and SyN whole-lung and lobar air trapping measurements achieved excellent agreement (intraclass correlation coefficients > 0.98). LungReg versus SyN area under the receiver operating characteristic curves for predicting GOLD stage were not statistically different (range, 0.88-0.95 vs 0.88-0.95, respectively; P = .31-.95)., Conclusion: CNN-based deformable lung registration is accurate and fully automated, with runtime feasible for clinical lobar air trapping quantification, and has potential to improve diagnosis of small airway diseases. Keywords: Air Trapping, Convolutional Neural Network, Deformable Registration, Small Airway Disease, CT, Lung, Semisupervised Learning, Unsupervised Learning Supplemental material is available for this article. © RSNA, 2021 An earlier incorrect version of this article appeared online. This article was corrected on December 22, 2021., Competing Interests: Disclosures of conflicts of interest: K.A.H. No relevant relationships. J.T. No relevant relationships. N.Y. No relevant relationships. T.R. No relevant relationships. A.H. Grants to institution from GE Healthcare, Bayer, and KA Imaging; co-founder of and shareholder in Arterys., (2021 by the Radiological Society of North America, Inc.)

Quantitative imaging measurements can be facilitated by artificial intelligence (AI) algorithms, but how they might impact decision-making and be perceived by radiologists remains uncertain. After creation of a dedicated inspiratory-expiratory CT examination and concurrent deployment of a quantitative AI algorithm for assessing air trapping, five cardiothoracic radiologists retrospectively evaluated severity of air trapping on 17 examination studies. Air trapping severity of each lobe was evaluated in three stages: qualitatively (visually); semiquantitatively, allowing manual region-of-interest measurements; and quantitatively, using results from an AI algorithm. Readers were surveyed on each case for their perceptions of the AI algorithm. The algorithm improved interreader agreement (intraclass correlation coefficients: visual, 0.28; semiquantitative, 0.40; quantitative, 0.84; P < .001) and improved correlation with pulmonary function testing (forced expiratory volume in 1 second-to-forced vital capacity ratio) (visual r = -0.26, semiquantitative r = -0.32, quantitative r = -0.44). Readers perceived moderate agreement with the AI algorithm (Likert scale average, 3.7 of 5), a mild impact on their final assessment (average, 2.6), and a neutral perception of overall utility (average, 3.5). Though the AI algorithm objectively improved interreader consistency and correlation with pulmonary function testing, individual readers did not immediately perceive this benefit, revealing a potential barrier to clinical adoption. Keywords: Technology Assessment, Quantification © RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: T.A.R. RSNA Machine Learning Committee member, unrelated to this work. K.A.H. No relevant relationships. S.J.K. Deputy editor of Radiology: Cardiothoracic Imaging. K.E.J. No relevant relationships. A.C.Y. No relevant relationships. S.S.B. No relevant relationships. L.D.H. No relevant relationships. A.H. Grants from GE Healthcare and Bayer; cofounder and shareholder in Arterys., (2021 by the Radiological Society of North America, Inc.)

Videofluoroscopy swallow studies (VFSS) and high-resolution manometry (HRM) methods complement to ascertain mechanisms of infant feeding difficulties. We hypothesized that: (a) an integrated approach (study: parent-preferred feeding therapy based on VFSS and HRM) is superior to the standard-of-care (control: provider-prescribed feeding therapy based on VFSS), and (b) motility characteristics are distinct in infants with penetration or aspiration defined as penetration-aspiration scale (PAS) score ≥ 2. Feeding therapies were nipple flow, fluid thickness, or no modification. Clinical outcomes were oral-feeding success (primary), length of hospital stay and growth velocity. Basal and adaptive HRM motility characteristics were analyzed for study infants. Oral feeding success was 85% [76-94%] in study (N = 60) vs. 63% [50-77%] in control (N = 49), p = 0.008. Hospital-stay and growth velocity did not differ between approaches or PAS ≥ 2 (all P > 0.05). In study infants with PAS ≥ 2, motility metrics differed for increased deglutition apnea during interphase (p = 0.02), symptoms with pharyngeal stimulation (p = 0.02) and decreased distal esophageal contractility (p = 0.004) with barium. In conclusion, an integrated approach with parent-preferred therapy based on mechanistic understanding of VFSS and HRM metrics improves oral feeding outcomes despite the evidence of penetration or aspiration. Implementation of new knowledge of physiology of swallowing and airway protection may be contributory to our findings., (© 2021. The Author(s).)

Objectives: According to LI-RADS, a major discriminating feature between hepatocellular carcinoma (HCC) and non-HCC malignancies is the subtype of arterial phase hyperenhancement (APHE). The aim of this study was to investigate whether APHE subtypes are consistent across multi-arterial phase (mHAP) MRI acquisitions while evaluating reader agreement. Secondarily, we investigated factors that may affect reader agreement for APHE subtype., Methods: In this retrospective study, consecutive patients with liver cirrhosis and focal observations who underwent mHAP were included. Five radiologists reviewed MR images in 2 reading sessions. In reading session 1, individual AP series were reviewed and scored for presence of APHE and subtype. In reading session 2, readers scored observations' major and ancillary features and LI-RADS category in the complete MRI examination. Reader agreement was calculated using Fleiss' kappa for binary outcomes and Kendall's coefficient of concordance for LI-RADS categories. Univariate mixed effects logistic regressions were performed to investigate factors affecting agreement., Results: In total, 61 patients with 77 focal observations were analyzed. Of observations unanimously scored as having APHE, 27.7% showed both rim and nonrim subtypes on mHAP. Inter-reader agreement for APHE subtype ranged from 0.49 (95% CI: 0.33, 0.64) to 0.57 (95% CI: 0.40, 0.74) between reading sessions. Observation size had a trend level effect on rim APHE agreement (p = 0.052)., Conclusion: Approximately 1/3 of observations demonstrated inconsistent APHE subtype during mHAP acquisition. Small lesions were particularly challenging. Further guidance on APHE subtype classification, especially when applied to mHAP, could be a focus of LI-RADS refinement., Key Points: • In a cohort of patients at risk for HCC, 28% of the observations showed inconsistent arterial phase hyperenhancement (APHE) subtypes (rim and nonrim) on multi-arterial phase imaging according to the majority score of 5 independent readers. • Inconsistent APHE subtypes may challenge reliable imaging diagnosis, i.e., LI-RADS categorization, of focal liver observations in patients at risk for HCC., (© 2021. European Society of Radiology.)

Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.

Purpose: To develop a deep learning-based algorithm to stage the severity of chronic obstructive pulmonary disease (COPD) through quantification of emphysema and air trapping on CT images and to assess the ability of the proposed stages to prognosticate 5-year progression and mortality., Materials and Methods: In this retrospective study, an algorithm using co-registration and lung segmentation was developed in-house to automate quantification of emphysema and air trapping from inspiratory and expiratory CT images. The algorithm was then tested in a separate group of 8951 patients from the COPD Genetic Epidemiology study (date range, 2007-2017). With measurements of emphysema and air trapping, bivariable thresholds were determined to define CT stages of severity (mild, moderate, severe, and very severe) and were evaluated for their ability to prognosticate disease progression and mortality using logistic regression and Cox regression., Results: On the basis of CT stages, the odds of disease progression were greatest among patients with very severe disease (odds ratio [OR], 2.67; 95% CI: 2.02, 3.53; P < .001) and were elevated in patients with moderate disease (OR, 1.50; 95% CI: 1.22, 1.84; P = .001). The hazard ratio of mortality for very severe disease at CT was 2.23 times the normal ratio (95% CI: 1.93, 2.58; P < .001). When combined with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging, patients with GOLD stage 2 disease had the greatest odds of disease progression when the CT stage was severe (OR, 4.48; 95% CI: 3.18, 6.31; P < .001) or very severe (OR, 4.72; 95% CI: 3.13, 7.13; P < .001)., Conclusion: Automated CT algorithms can facilitate staging of COPD severity, have diagnostic performance comparable with that of spirometric GOLD staging, and provide further prognostic value when used in conjunction with GOLD staging. Supplemental material is available for this article. © RSNA, 2021See also commentary by Kalra and Ebrahimian in this issue., Competing Interests: Disclosures of Conflicts of Interest: K.A.H. disclosed no relevant relationships. N.Y. disclosed no relevant relationships. T.R. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution has a patent with Cardiac MRI Software. Other relationships: disclosed no relevant relationships. D.J.C. disclosed no relevant relationships. S.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: deputy editor for Radiology: Cardiothoracic Imaging. Other relationships: disclosed no relevant relationships. D.A.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution participated in the Boehringer Ingelheim Footprints study. Other relationships: disclosed no relevant relationships. A.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a consultant for Arterys, institution received grants from GE Healthcare and Bayer, gave lectures for Bayer, is the founder of and a shareholder in Arterys, received travel assistance from GE Healthcare. Other relationships: disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Objective: To test the hypothesis that a feeding bundle concurrent with acid suppression is superior to acid suppression alone in improving gastroesophageal reflux disease (GERD) attributed-symptom scores and feeding outcomes in neonatal ICU infants., Methods: Infants (N = 76) between 34 and 60 weeks' postmenstrual age with acid reflux index > 3% were randomly allocated to study (acid-suppressive therapy + feeding bundle) or conventional (acid-suppressive therapy only) arms for 4 weeks. Feeding bundle included: total fluid volume < 140 mL/kg/day, fed over 30 min in right lateral position, and supine postprandial position. Primary outcome was independent oral feeding and/or ≥6-point decrease in symptom score (I-GERQ-R). Secondary outcomes included growth (weight, length, head circumference), length of hospital stay (LOHS, days), airway (oxygen at discharge), and developmental (Bayley scores) milestones., Results: Of 688 screened: 76 infants were randomized and used for the primary outcome as intent-to-treat, and secondary outcomes analyzed for 72 infants (N = 35 conventional, N = 37 study). For study vs. conventional groups, respectively: (a) 33% (95% CI, 19-49%) vs. 44% (95% CI, 28-62%), P = 0.28 achieved primary outcome success, and (b) secondary outcomes did not significantly differ (P > 0.05)., Conclusions: Feeding strategy modifications concurrent with acid suppression are not superior to PPI alone in improving GERD symptoms or discharge feeding, short-term and long-term outcomes., Impact: Conservative feeding therapies are thought to modify GERD symptoms and its consequences. However, in this randomized controlled trial in convalescing neonatal ICU infants with GERD symptoms, when controlling for preterm or full-term birth and severity of esophageal acid reflux index, the effectiveness of acid suppression plus a feeding modification bundle (volume restriction, intra- and postprandial body positions, and prolonged feeding periods) vs. acid suppression alone, administered over a 4-week period was not superior in improving symptom scores or feeding outcomes. Restrictive feeding strategies are of no impact in modifying GERD symptoms or clinically meaningful outcomes. Further studies are needed to define true GERD and to identify effective therapies in modifying pathophysiology and outcomes. The improvement in symptoms and feeding outcomes over time irrespective of feeding modifications may suggest a maturational effect. This study justifies the use of placebo-controlled randomized clinical trial among NICU infants with objectively defined GERD.

Introduction: Aims were to test hypothesis that esophageal provocation-induced reflexes are superior with acid suppression plus feeding modifications vs acid suppression alone among infants treated for gastroesophageal reflux disease (GERD)., Methods: Infants (N = 49, 41.3 ± 2.6 of postmenstrual age) with acid reflux index >3% underwent longitudinal motility testing (weeks 0 and 5) with graded midesophageal provocation to test randomly allocated therapies (4 weeks' proton pump inhibitor [PPI] ± feeding modifications) on sensory-motor aerodigestive reflexes. Feeding modification included restricted fluid volume <140 mL/kg per day, fed over 30 minutes in right lateral position and supine postprandial position. Primary motility outcome was frequency-occurrence of peristaltic reflex. Secondary outcomes included upper esophageal sphincter contractile reflex, lower esophageal sphincter (LES) relaxation reflex, respiratory change, and symptom characteristics., Results: Treatment groups did not differ for primary outcome (odds ratio = 0.8, 95% confidence interval 0.4-1.6, P = 0.99) or secondary outcomes (all P > 0.05). For both treatment groups at follow-up, distal esophageal contraction and LES tone decreased, and LES relaxation reflex occurrence is less frequent (all P < 0.05). In a subgroup analysis, comparing infants with PPI washout (N = 40) vs with continued (N = 9) PPI therapy, no differences were noted for aerodigestive reflex response frequency-occurrence (all P > 0.05)., Discussion: In infants with GERD, feeding modification with acid suppression is not superior to acid suppression alone in modifying aerodigestive reflexes (frequency, sensation, or magnitude). Contiguous areas targeted by GER, i.e., LES and distal esophageal functions, worsened at follow-up for both groups despite PPI therapy. Maturation is likely the key factor for GERD resolution in infants, justifying the use of placebo in clinical trials for objectively determined GERD.

Aim: To compare the changes in visceral adipose tissue (VAT), liver fat fraction, and liver stiffness using quantitative magnetic resonance imaging (MRI) during a very-low-calorie ketogenic (VLCK) diet and a standard low-calorie diet (LC)., Materials and Methods: The study involved secondary analysis of prospective collected clinical data. Patients undergoing weight loss interventions were randomised to either a LC or a VLCK diet. VAT, liver fat fraction, and stiffness were measured at baseline and after 2 months., Results: Forty-six patients were included; 39 patients were evaluated at baseline and at 2 months follow-up. Mean weight loss was -9.7±3.8 kg (interquartile range [IQR]: -12.3; -7 kg) in the VLCK group and -1.67±2.2 kg (IQR: -3.3, -0.1 kg) in the LC group (p<0.0001). Mean VAT reductions were -39.3±40 cm 2 (IQR: -52, -10 cm 2 ) and -12.5±38.3 cm 2 (IQR: -29, 5 cm 2 ; p=0.0398), and mean liver proton density fat fraction (PDFF) reductions were -4.77±4.2% (IQR: -7.3, -1.7%) and -0.79±1.7%, (IQR: -1.8, -0.4%; p<0.005) in the VLCK group and in the LC group, respectively. No significant changes in liver stiffness occurred from baseline to follow-up., Conclusion: A VLCK diet resulted in greater weight loss than a standard low-calorie diet and in significantly greater reduction in liver PDFF. As anthropometric measurements may not correlate with liver fat changes, it may be advantageous to include quantitative MRI to the monitoring strategies of patients undergoing weight-loss programmes., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Gastroesophageal reflux (GER) is considered physiologic and is a normal process; whereas, when aerodigestive consequences are associated, it is often interpreted as GER disease (GERD). However, the distinction between them remains a challenge in infants in the NICU. Reflux-type of symptoms are heterogeneous, and often managed with changes in diet, feeding methods, and acid-suppressive therapy; all these empiric therapies lack objectivity; hence, practice variation is universal. We clarify the current controversies, explain the potential role of GERD in causing symptoms and complications, and highlight current advances. The evidence basis for the diagnostic strategies is discussed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To develop and evaluate the performance of a fully-automated convolutional neural network (CNN)-based algorithm to evaluate hepatobiliary phase (HBP) adequacy of gadoxetate disodium (EOB)-enhanced MRI. Secondarily, we explored the potential of the proposed CNN algorithm to reduce examination length by applying it to EOB-MRI examinations., Methods: We retrospectively identified EOB-enhanced MRI-HBP series from examinations performed 2011-2018 (internal and external datasets). Our algorithm, comprising a liver segmentation and classification CNN, produces an adequacy score. Two abdominal radiologists independently classified series as adequate or suboptimal. The consensus determination of HBP adequacy was used as ground truth for CNN model training and validation. Reader agreement was evaluated with Cohen's kappa. Performance of the algorithm was assessed by receiver operating characteristics (ROC) analysis and computation of the area under the ROC curve (AUC). Potential examination duration reduction was evaluated descriptively., Results: 1408 HBP series from 484 patients were included. Reader kappa agreement was 0.67 (internal dataset) and 0.80 (external dataset). AUCs were 0.97 (0.96-0.99) for internal and 0.95 (0.92-96) for external and were not significantly different from each other (p = 0.24). 48 % (50/105) examinations could have been shorter by applying the algorithm., Conclusion: A proposed CNN-based algorithm achieves higher than 95 % AUC for classifying HBP images as adequate versus suboptimal. The application of this algorithm could potentially shorten examination time and aid radiologists in recognizing technically suboptimal images, avoiding diagnostic pitfalls., Competing Interests: Declaration of Competing Interest All authors or institutions involved in this work have no conflicts of interest or industry support to disclose with regard to the current manuscript. This includes financial or personal relationships that inappropriately influence his or her actions within 3 years of the work beginning submitted., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Liver alignment between series/exams is challenged by dynamic morphology or variability in patient positioning or motion. Image registration can improve image interpretation and lesion co-localization. We assessed the performance of a convolutional neural network algorithm to register cross-sectional liver imaging series and compared its performance to manual image registration., Methods: Three hundred fourteen patients, including internal and external datasets, who underwent gadoxetate disodium-enhanced magnetic resonance imaging for clinical care from 2011 to 2018, were retrospectively selected. Automated registration was applied to all 2,663 within-patient series pairs derived from these datasets. Additionally, 100 within-patient series pairs from the internal dataset were independently manually registered by expert readers. Liver overlap, image correlation, and intra-observation distances for manual versus automated registrations were compared using paired t tests. Influence of patient demographics, imaging characteristics, and liver uptake function was evaluated using univariate and multivariate mixed models., Results: Compared to the manual, automated registration produced significantly lower intra-observation distance (p < 0.001) and higher liver overlap and image correlation (p < 0.001). Intra-exam automated registration achieved 0.88 mean liver overlap and 0.44 mean image correlation for the internal dataset and 0.91 and 0.41, respectively, for the external dataset. For inter-exam registration, mean overlap was 0.81 and image correlation 0.41. Older age, female sex, greater inter-series time interval, differing uptake, and greater voxel size differences independently reduced automated registration performance (p ≤ 0.020)., Conclusion: A fully automated algorithm accurately registered the liver within and between examinations, yielding better liver and focal observation co-localization compared to manual registration.

Purpose: To evaluate the association between optical coherence tomography angiography (OCTA) macular and circumpapillary vessel density and visual field mean deviation (MD) in advanced primary open angle glaucoma., Design: Cross-sectional study., Methods: Macula (superficial layer) and optic nerve head (ONH) with capillary density (CD) and without vessel density (VD) automated removal of large vessels OCTA of 34 eyes (34 patients, MD < -10 dB) were investigated as macula whole image VD (wiVD), parafoveal VD (pfVD), ONH wiVD, wiCD, circumpapillary VD, and cpCD. Spectral domain OCT circumpapillary retinal nerve fiber layer, macular ganglion cell complex, and ganglion cell inner plexiform layer were also analyzed., Results: Macular and ONH VD decreased significantly with worsening MD. Each 1-dB decrease in MD was associated with a reduction of 0.43% and 0.46% for macular wiVD and pfVD with R 2 of 0.28 and 0.27, respectively (all P < .01). The association between MD and VD was strongest for measures of ONH with large vessels removed, wiCD, and cpCD, followed by wiVD and circumpapillary VD with R 2 of 0.26, 0.22, 0.17, 0.14, and a VD reduction of 0.43%, 0.51%, 0.33%, and 0.40%, respectively (all P < .02). There was a reduction of 1.19 μm in Avanti parafoveal ganglion cell complex, 1.13 μm in Spectralis ganglion cell inner plexiform layer, and 1.01 μm in Spectralis circumpapillary retinal nerve fiber layer, with R 2 of 0.19 (P = .006), 0.23 (P = .002), and 0.24 (P = .002), respectively., Conclusions: ONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Maturation of pharyngeal swallowing during neonatal oral feeding is unknown. Our objective was to evaluate pharyngeal functioning using high-resolution manometry (HRM) during nutritive oral stimulus and test the hypothesis that pharyngeal contractility and regulation are distinct in preterm-born infants., Methods: High-resolution manometry data during oral milk feeding were analyzed for pharyngeal contractile (PhCI, mm Hg cm s) and regulatory (number and frequency of pharyngeal contractions and bursts, pharyngeal activity-to-quiescence ratio, upper esophageal sphincter nadir pressure) characteristics in 23 preterm (<38 weeks' gestation) and 18 full-term-born infants at term maturation. Mixed linear models and stepwise regression methods were used., Results: Despite more oral feeding experiences (P < 0.05), preterm infants (vs full-term), consumed less milk volume (P < 0.001), had lesser pharyngeal contractions within bursts (P = 0.04), lower pharyngeal contraction frequency (P < 0.01), and lower pharyngeal activity (P = 0.03), but higher PhCI per individual contraction (P = 0.01). PhCI is higher for longer PMA (P < 0.05), higher UES nadir pressures (P < 0.05), and lower pharyngeal contraction frequency (P < 0.05)., Conclusions: Nutritive oral milk stimulus provoked pharyngeal contractility characteristics is distinct in preterm-born. Despite more oral nutritive experiences, preterm infants had underdeveloped excitatory and inhibitory rhythmic activity. Cranial nerve IX and X effects on sensory-motor responses and feedback (excitation-inhibitory rhythm regulation) remain immature among preterm-born even at full-term maturational status. We speculate the relationship between PhCI and UES regulatory activity contributes to the observed differences in preterm and full-term infants., (© 2019 John Wiley & Sons Ltd.)

Objective: To test whether symptom generation in infants is related to the severity of gastroesophageal reflux disease (GERD) symptoms as determined by the Acid Reflux Index (ARI), stimulus media, and stimulus volume during provocative esophageal manometry., Study Design: Symptomatic neonates (n = 74) born at a median of 28.9 weeks gestation (range, 23.4-39.4 weeks) were studied at a median of 41.0 weeks (range, 34.6-48.0 weeks) postmenstrual age using 24-hour pH-impedance methods to determine ARI severity, followed by provocative esophageal manometry with graded mid-esophageal infusions (0.1-5.0 mL) of air, water, and apple juice. Peristaltic reflexes and symptom characteristics were compared among ARI severity categories using linear mixed models and generalized estimating equations., Results: The effects of 2635 separate esophageal stimuli on reflexes and symptoms were analyzed. Peristaltic reflexes occurred in 1880 infusions (71%), and physical, cardiorespiratory, sensory symptoms were seen in 439 infusions (17%). Symptom prevalence did not differ across the ARI severity categories (ARI <3, 18%; ARI 3-7, 17%; ARI >7, 16%; P = 1.0). Symptom and peristaltic responses increased with incremental stimulus volumes (all media, P < .001)., Conclusions: Symptoms and peristaltic reflexes are manifestations of the recruitment of several neurosensory and neuromotor pathways evoked by mid-esophageal infusions. ARI severity grade plays no role in symptom generation, indicating that GERD should not be diagnosed and severity should not be assigned based on symptoms alone. An increase in symptom occurrence was noted with increasing stimulus volumes, which provided increased activation of receptors, afferents, and efferents in evoking peristaltic clearance reflexes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In adults, distal baseline impedance (BI) is a determinant of esophageal mucosal integrity with values <900 Ω indicating inflammation. Relationships between acid gastroesophageal reflux (GER) and BI in neonates are unclear., Methods: NICU infants (N = 198, 30.4 ± 0.3 weeks gestation) were evaluated at 43 ± 0.4 weeks postmenstrual age using 24-h pH-impedance. Ten randomly selected 1-min windows during rest from the distal impedance channel (Z6) were averaged. Chi-square, t-tests, and ANOVA were used to compare pH-impedance and symptom characteristics by BI severity (BI < 900 Ω, BI 900-2000 Ω, BI > 2000 Ω). Regression analysis was used to identify potential contributing factors of BI., Results: In BI < 900 Ω: (1) pH-impedance characteristics were increased (acid reflux event frequency, duration, and severity, all P < 0.05 vs. BI > 2000 Ω), and (2) positive symptom correlations were noted with bolus (73%) and acid events (55%). Significant predictors of BI included chronological age, acid reflux index, and BPD diagnosis (all P < 0.05)., Conclusions: Low BI is associated with prolonged acid exposure, delayed clearance, and greater aerodigestive symptom prevalence, likely associated with inflammation and or increased mucosal permeability. BI > 2000 Ω likely involves little or no inflammation because acid exposure is minimal. Combination of SAP, pH-impedance metrics, and BI along with the clarification of dysmotility mechanisms provides the rationale for personalized anti-reflux therapies as needed.

Background: A common osmolality threshold for feedings is to stay <450 mOsm/kg for normal infants. Preterm formulas are frequently modified to improve growth, modify nutrition, and manage gastroesophageal reflux (GER) or dysphagia. Relationships between osmolality and additives to ready-to-feed preterm formulas are unclear. Our aims were to evaluate and compare the effects of caloric density, thickening agent recipes, and supplements to ready-to-feed preterm formula on osmolality., Methods: A freezing point osmometer was used to measure the osmolality of 47 preterm infant formula combinations with varying caloric densities (ready-to-feed 22 and 30 cal/oz), thickening agents (rice vs oatmeal cereal), thickener amounts (0.0, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 tsp/oz), and combinations of supplements (saline, iron, vitamin D, or multivitamin). Ten samples per combination were tested using a 10-μL pipette. Comparisons were made using analysis of variance and t-tests for group and pair-wise comparisons, respectively., Results: A total of 470 osmolality samples were analyzed: (1) raters had high agreement (r = 0.98; P < .001); (2) for every 0.5 tsp/oz of thickener, the osmolality increases by 30 mOsm/kg (P < .001); (3) osmolality was higher with the oatmeal (vs rice) thickening agent (P < .001); and (4) vitamin and electrolyte supplement combinations increase osmolality., Conclusions: Alteration of ready-to-feed preterm formulas may significantly increase osmolality and have unintended consequences. Caution and monitoring should be exercised with modifying ready-to-feed preterm formulas for regurgitation, rumination, GER, dysphagia, feeding intolerance, or emesis. This study supports the concept of achieving volume tolerance before further manipulation of additives., (© 2018 American Society for Parenteral and Enteral Nutrition.)

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

Background: Pharyngeal contractility is critical for safe bolus propulsion. Pharyngeal contractile vigor can be measured by Pharyngeal Contractile Integral (PhCI): product of mean pharyngeal contractile amplitude, length, and duration. We characterized PhCI in neonates and examined the hypothesis that PhCI differs with mode of stimulation., Methods: Nineteen neonates born at 38.6 (34-41) weeks gestation were evaluated at 42.9 (40.4-44.0) weeks postmenstrual age using high-resolution manometry (HRM). PhCI was calculated using: (a) Conventional and (b) Automated Swallow Detection algorithm (ASDA) methods. Contractility metrics of all pharyngeal regions were examined using mixed statistical models during spontaneous and adaptive state (pharyngeal and oral stimulus) swallowing., Results: PhCI of oral stimuli swallows were distinct from pharyngeal stimuli and spontaneous swallows (P < 0.05). Correlation between conventional and ASDA methods was high (P < 0.001). PhCI increased with swallows for pharyngeal stimulation (P < 0.05) but remained stable for swallows with oral stimulation. PhCI differed between proximal and distal pharynx (P < 0.001)., Conclusions: PhCI is a novel reliable metric capable of distinguishing (1) proximal and distal pharyngeal activity, (2) effects of oral and pharyngeal stimulation, and (3) effects of prolonged stimulation. Changes in pharyngeal contractility with maturation, disease, and therapies can be examined with PhCI.

Background: The definition of severe bronchopulmonary dysplasia (sBPD) is based on respiratory support needs. The management of a patient with sBPD remains empirical and is highly variable among providers. Our objective in this study was to test the hypothesis that infant pulmonary function testing (iPFT) would reveal distinct phenotypes in patients with established sBPD during the initial NICU stay., Methods: A prospective cohort study with data prospectively collected on infants with sBPD from May 1, 2003, to June 30, 2016. iPFT data were used to classify the patients as obstructive, restrictive, or mixed., Results: The median gestational age at birth was 25 weeks (interquartile range [IQR], 24-27 weeks) and the median birth weight was 707 g (IQR, 581-925 g). At the time of iPFT, the median postmenstrual age was 52 weeks (IQR, 45-63 weeks), and the median weight was 4.4 kg (IQR, 3.7-6.0 kg). There were 56 (51%) patients with obstructive, 44 (40%) with mixed, and 10 (9%) with restrictive phenotypes. Moderate or severe obstruction was seen in 86% of the obstructive group and 78% of the mixed group. Of the restrictive patients, 70% had moderate and 30% had mild restriction. Bronchodilator response was seen in 74% of obstructive, 63% of mixed, and 25% of restrictive patients., Conclusions: Our findings reveal that sBPD as it is currently defined includes distinct phenotypes. Future researchers of diagnostic approaches to this population should consider the development of bedside tests to define phenotypes, and researchers in future therapeutic trials should consider the use of pulmonary function phenotyping in patient recruitment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Purpose: To compare optical coherence tomography angiography (OCTA) measured macular vessel density and spectral domain optical coherence tomography (SDOCT) measured macular ganglion cell complex (GCC) thickness in primary open-angle glaucoma eyes with and without focal lamina cribrosa (LC) defects., Methods: In this cross-sectional, case-control study of patients with primary open-angle glaucoma, 46 eyes of 46 patients with LC defects and 54 eyes of 54 patients without observable LC defects were included. OCTA and SDOCT imaging were performed on the same day by the same operator. Perimetry and swept-source OCT testing used to identify LC defects were conducted within 6 months of OCTA and SDOCT testing. Global and local parafoveal vessel density and macular GCC thickness were compared between study groups., Results: Glaucoma severity was similar between groups (SAP mean deviation=-5.63 and -4.64 dB for eyes with and without LC defects, respectively; P=0.40). Global and local measured parafoveal vessel density was similar between groups (all P≥0.11). GCC focal loss volume was higher in eyes with LC defects than eyes without LC defects (7.2% and 4.97%, respectively; P=0.03). In addition, GCC focal loss volume was topographically related to defect location in LC defect eyes., Conclusions: Although OCTA macular vessel density was not significantly different between eyes with and without LC defects, focal GCC loss in eyes with LC defects was different. This highlights the importance of not relying solely on vessel density measurements for determining macular changes for diagnosing and detecting glaucomatous progression.

Pharyngeal-provocation induced aerodigestive symptoms in infants remain an enigma. Sources of pharyngeal provocation can be anterograde as with feeding, and retrograde as in gastroesophageal reflux. We determined maturational and dose-response effects of targeted pharyngeal-stimulus on frequency, stability, and magnitude of pharyngeal and respiratory waveforms during multiple pharyngeal swallowing responses in preterm-born infants when they were of full-term postmenstrual age (PMA). Eighteen infants (11 male) were studied longitudinally at 39.8 ± 4.8 weeks PMA (time-1) and 44.1 ± 5.8 weeks PMA (time-2). Infants underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflow thermistor methods to test sensory-motor interactions between the pharynx, esophagus, and airway. Linear mixed models were used and data presented as mean ± SEM or %. Overall, responses to 250 stimuli were analyzed. Of the multiple pharyngeal swallowing responses (n = 160), with maturation (a) deglutition apnea duration decreases (p < 0.01), (b) number of pharyngeal waveform peaks and duration decreases for initial responses (p < 0.01), and subsequent responses have lesser variation and greater stability (p < 0.01). With increment in stimulus volumes we noted (a) increased prevalence (%) of pharyngeal responses (p < 0.05), (b) increased number of pharyngeal peaks (p < 0.05), yet pharyngeal frequency (Hz), variability, and stability remain unaffected (p > 0.05), and (c) respiratory changes were unaffected (p > 0.05). Initial and subsequent pharyngeal responses and respiratory rhythm interactions become more distinct with maturation. Interval oromotor experiences and volume-dependent increase in adaptive responses may be contributory. These mechanisms may be important in modulating and restoring respiratory rhythm normalcy.

To quantify and compare maximal extent (height) of acid reflux events (AREs) on symptom generation in dysphagic neonates. Dysphagic neonates (N = 53), born at 30 ± 5.3 weeks gestation, underwent 24-hour pH-impedance study for the evaluation of troublesome symptoms purported to be due to gastroesophageal reflux disease (GERD). AREs (pH < 4 for >4 s) detected by impedance (Z) were categorized by maximal extent as refluxate reaching distal (Z6, Z5), middle (Z4, Z3), or proximal (Z2, Z1) impedance channels. AREs reaching the pH sensor only were categorized as distal. Symptom correlation (%, symptom index, symptom sensitivity index, and symptom associated probability) and temporal characteristics (clearance times) of AREs were analyzed using linear mixed and GEE models comparing height categories presented as mean ± SEM, median (IQR), and OR (95% CI). Of the 2003 AREs, 1) distal extent AREs (n = 1642) had increased frequency (p < 0.05), decreased ACT (p < 0.05), and decreased acidity (p < 0.05); 2) in middle and proximal AREs, acid clearance was longer than bolus clearance, (p < 0.01); and 3) the odds of having cardiorespiratory (cough or sneeze) symptoms are increased with proximal and middle AREs (p < 0.05). Most proximal ascent of AREs into middle or proximal esophagus likely activates protective aerodigestive reflexes (peristalsis) or vigilant states to facilitate bolus and chemical clearance. Heightened esophageal sensitivity, acid neutralization delays, or clearance mechanism delays may accentuate multi-systemic troublesome symptoms.

Background: Development of pharyngo-esophageal protective reflexes among infants with hypoxic ischemic encephalopathy (HIE) is unclear. Our aim was to distinguish these reflexes from controls and examine the maturational changes in HIE infants., Methods: We evaluated 14 HIE infants (seven males) at 41.4±0.6 (HIE Time-1) and 46.5±0.6 (HIE Time-2) weeks postmenstrual age (PMA). Seven controls (three males) were evaluated at 43.5±1.3 weeks PMA. Graded pharyngeal stimulation with liquids (0.1, 0.3, 0.5 mL in triplicate) concurrent with high-resolution manometry was used to analyze sensory-motor components of pharyngeal reflexive swallowing (PRS), upper esophageal sphincter (UES), contractile reflex (PUCR), and esophageal body characteristics. Linear mixed and generalized estimating equation models were used for comparison among groups., Key Results: Compared to controls, HIE infants (Time-1 and Time-2) exhibited decreased number of pharyngeal peaks and latency to terminal swallow. HIE Time-1 infants showed increased UES resting tone and distal latency, compared to controls and HIE Time-2. Contractile vigor was increasingly abnormal during maturation, compared to healthy controls. Threshold volumes and frequency distribution of primary responses (PRS: PUCR: None) were not significant among all groups., Conclusions & Inferences: Compared to controls, HIE infants display significant hypertonicity of skeletal muscle components, impairment of pharyngeal provocation-induced reflexes and smooth muscle contractile vigor, reflecting poor propagation with maturation. These mechanisms may be responsible for inadequate clearance of secretions, ascending refluxate, and oropharyngeal bolus in HIE infants., (© 2017 John Wiley & Sons Ltd.)

Palmar and plantar grasp are the foremost primitive neonatal reflexes and functions. Persistence of these reflexes in infancy is a sign of evolving cerebral palsy. Our aims were to establish measurement feasibility in a clinical setting and to characterize changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD) concentration in the bilateral frontoparietal cortex in unsedated neonates at the crib-side using functional near-infrared spectroscopy (fNIRS). We hypothesized that bilateral concentration changes will occur upon somatic central and peripheral somatic stimulation. Thirteen preterm neonates (five males) underwent time 1, and six (two males) returned for time 2 (mean [Formula: see text] and 47.0 weeks, respectively). Signals from a total of 162 somatic stimuli responses were measured. Response amplitude, duration, and latency were log-transformed and compared between palmar, plantar, and oromotor stimuli using linear mixed models, adjusted for cap, electroencephalogram abnormality, time (1 versus 2), and Sarnat score, if necessary. The oromotor stimulus resulted in a 50% greater response than the palmar or plantar stimuli for HbO left and right hemisphere duration ([Formula: see text]). There were no other statistically significant differences between stimuli for any other outcome ([Formula: see text]). Utilizing fNIRS in conjunction with occupational and physical therapy maneuvers is efficacious to study modifiable and restorative neurophysiological mechanisms.

Aim: Although the coordination of sucking and swallowing is critical for successful oral intake in neonates, the mechanisms that facilitate this coordination are not well understood. This investigation sought to clarify the mechanisms that facilitate this coordination, by comparing sucks that were coordinated with swallows and sucks that were completed in isolation., Methods: Ten neonates with a median gestational age of 28.2 weeks, ranging from 27.0 to 35.0 weeks, were recruited from the neonatal nurseries at Nationwide Children's Hospital, Columbus, Ohio, USA. They were evaluated while bottle-feeding at term gestation for differences in characteristics between sucks that were coupled and not coupled with swallows. Suction was evaluated using an intra-oral pressure transducer, and swallows were identified using a micromanometry pharyngeal catheter. Linear mixed models were applied to distinguish sucking characteristics., Results: Suction exhibited an antiphase relationship with the generation and release of positive pharyngeal pressure during the swallow. Coupled sucks had lower suction generation and release rates (p < 0.0001), lower suction amplitude (p = 0.004), longer suction duration (p < 0.0001) and higher milk ejection pressure (p < 0.0001)., Conclusion: The coordination of unique sucking and swallowing movement patterns may be achieved by the infant adapting sucking kinematics around the lingual patterns that facilitate the pharyngeal swallow., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones., (Copyright © 2016 the American Physiological Society.)

Background: Cough and deglutition are protective mechanisms that defend against aspiration. We identified mechanisms associated with cough provocation as well as those associated with cough resolution in infants with bronchopulmonary dysplasia (BPD)., Methods: Manometry signatures of cough were recognized in 16 premature infants with BPD undergoing concurrent esophageal manometry, respiratory inductance plethysmography, and nasal air flow measurements. Pretussive and post-tussive pharyngo-esophageal motility changes were analyzed. Mechanisms associated with cough and mechanisms that restored respiratory and esophageal normalcy were analyzed., Results: We analyzed 312 cough events during 88 cough clusters; 97% were associated with recognizable manometric patterns. Initial mechanisms related with coughing included nonpropagating swallow (59%), upper esophageal sphincter (UES) reflex contraction (18%), and lower esophageal sphincter (LES) relaxation (14%). UES and LES dysfunction was present in 69% of nonpropagating swallow-associated cough clusters. Mechanisms restoring post-tussive normalcy included primary peristalsis (84%), secondary peristalsis (8%), and none recognized (8%). UES contraction reflex was associated with cough clusters more frequently in infants on nasal continuous positive airway pressure (NCPAP) (OR = 9.13, 95% CI = 1.88-44.24)., Conclusion: Cough clusters in infants with BPD had identifiable etiologies associated with esophageal events; common initial mechanisms were of upper aerodigestive origin, while common clearing mechanisms were peristaltic reflexes.

Objective: To test the hypothesis that proximal aerodigestive clearance mechanisms mediated by pharyngoesophageal motility during spontaneous respiratory events (SREs) are distinct in infants with apparent life threatening events (ALTEs)., Study Design: Twenty infants (10 with proven ALTE, 10 healthy controls) had pharyngoesophageal manometry to investigate motility changes concurrent with respiratory events detected by respiratory inductance plethysmography and nasal thermistor methods. We measured changes in resting upper esophageal and lower esophageal sphincter pressures, esophageal peristalsis characteristics, and gastroesophageal reflux. Statistical analysis included mixed models; data presented as mean±SD, median (range), or percentage., Results: Infants with ALTE (vs controls) had: (1) delays in restoring aerodigestive normalcy as indicated by more frequent (P=.03) and prolonged SREs (P<.01); (2) a lower magnitude of protective upper esophageal sphincter contractile reflexes (P=.01); (3) swallowing as the most frequent esophageal event associated with SREs (84%), with primary peristalsis as the most prominent aerodigestive clearance mechanism (64% vs 38%, P<.01); (4) a higher proportion of failed esophageal propagation (10% vs 0%, P=.02); and (5) more frequent mixed apneic mechanisms (P<.01) and more gasping breaths (P=.04)., Conclusions: In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility characterized by frequent primary peristalsis and significant propagation failure, thus suggestive of dysfunctional regulation of swallow-respiratory junction interactions. Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Central and peripheral neural regulation of swallowing and aerodigestive reflexes is unclear in human neonates. Functional near infrared spectroscopy (NIRS) is a noninvasive method to measure changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD). Pharyngoesophageal manometry permits evaluation of aerodigestive reflexes. Modalities were combined to investigate feasibility and to test neonatal frontoparietal cortical changes during pharyngoesophageal (visceral) stimulation and/or swallowing. Ten neonates (45.6 ± 3.0 wk postmenstrual age, 4.1 ± 0.5 kg) underwent novel pharyngoesophageal manometry concurrent with NIRS. To examine esophagus-brain interactions, we analyzed cortical hemodynamic response (HDR) latency and durations during aerodigestive provocation and esophageal reflexes. Data are presented as means ± SE or percent. HDR rates were 8.84 times more likely with basal spontaneous deglutition compared with sham stimuli (P = 0.004). Of 182 visceral stimuli, 95% were analyzable for esophageal responses, 38% for HDR, and 36% for both. Of analyzable HDR (n = 70): 1) HbO concentration (μmol/l) baseline 1.5 ± 0.7 vs. 3.7 ± 0.7 poststimulus was significant (P = 0.02), 2) HbD concentration (μmol/l) between baseline 0.1 ± 0.4 vs. poststimulus -0.5 ± 0.4 was not significant (P = 0.73), and 3) hemispheric lateralization was 21% left only, 29% right only, and 50% bilateral. During concurrent esophageal and NIRS responses (n = 66): 1) peristaltic reflexes were present in 74% and HDR in 61% and 2) HDR was 4.75 times more likely with deglutition reflex vs. secondary peristaltic reflex (P = 0.016). Concurrent NIRS with visceral stimulation is feasible in neonates, and frontoparietal cortical activation is recognized. Deglutition contrasting with secondary peristalsis is related to cortical activation, thus implicating higher hierarchical aerodigestive protective functional neural networks., (Copyright © 2014 the American Physiological Society.)