Utilizing Fetal Echocardiography to Risk Stratify and Predict Neonatal Outcomes in Fetuses Diagnosed with Congenital Heart Disease.

OBJECTIVE: Risk stratification of fetuses diagnosed with congenital heart disease (CHD) helps provide a delivery plan and prepare families and medical teams on expected course in the delivery room. Our aim was to assess the accuracy of echocardiographically determined risk-stratification assignments in predicting postnatal cardiac outcomes beyond the delivery room. STUDY DESIGN: This was a retrospective study at a single center evaluating all fetuses with CHD who were risk-stratified by echocardiographically determined level of care (LOC) assignment, ranging from 1a (lowest risk) to 4 (highest risk). All data were collected from January 1, 2017, to November 1, 2021. Outcomes included any unexpected cardiac interventions and neonatal clinical outcomes including in-hospital mortality, the need for prostaglandins or inotropes, and defined critical illness. These outcomes were assessed for each LOC assignment by Fisher's exact test. RESULTS: Out of 817 patients assigned a LOC, a total of 747 fetuses were included in our final cohort with a separate subanalysis of 70 fetuses diagnosed with coarctation of the aorta. The sensitivity and specificity were high for all LOC levels in predicting delivery room needs (93-100%). Higher LOC levels (3-4) had a lower positive predictive value (66-67%) indicating a high false-positive rate. Subjects with higher LOC assignments had a greater frequency of critical illness, hospital mortality, need for inotropes, need for neonatal surgical or catheterization interventions, and need for prostaglandins (p < 0.001 for all outcomes). A post-hoc analysis reviewing LOC assignments revealed a greater tendency to over-assign LOC at higher assignments (19% for LOC 3 and 4) compared to lower assignments (4% for LOC 1 and 2). CONCLUSION: Risk stratification based on fetal echocardiography can predict neonatal clinical outcomes and acuity of postnatal management needs. However, there is greater variability in expected clinical events and an expected degree of false positives for those with higher LOC assignments. KEY POINTS: · Risk stratification utilizing fetal echocardiography can be used to predict neonatal needs.. · Complex heart disease has lower positive predictive value in predicting postnatal clinical needs.. · There is a tendency to over-assign risk of acute hemodynamic instability for complex heart disease.. · False positives are expected when planning high-risk deliveries to avoid compromising situations..

Prevalence of pulmonary hypertension in obstructive sleep apnea and relation to disease severity.

STUDY OBJECTIVES: The purpose of this study is to examine the prevalence of pulmonary hypertension (PHTN) in children with obstructive sleep apnea (OSA) using echocardiographic (ECHO) parameters and to examine ECHO findings as they relate to severity of OSA. METHODS: A retrospective cohort study of subjects with OSA undergoing polysomnogram (PSG) and ECHO within 30 days of each other, between 01/01/15 - 12/31/20 was performed, excluding cardiac disease. ECHO evidence of PHTN was defined as ≥ 2 of the following: tricuspid regurgitation (TR) velocity > 3.0 m/sec, pulmonary acceleration/ejection time (AT/ET) ratio < 0.3, left ventricular eccentricity index (EI) > 1.5, right ventricular (RV) dysfunction or abnormal geometry. ECHO parameters were compared to OSA severity using obstructive apnea-hypopnea index (AHI), % time with oxygen saturation < 90%, and % time with end-tidal carbon dioxide > 50 mmHg. Odds ratios were calculated for each comorbidity to evaluate for risk factors. RESULTS: Of 509 subjects, 4.3% were found to have echocardiographic evidence of PHTN. Neither oAHI severity, nor worsening hypoxemia or hypercarbia correlated with worsening ECHO parameters. Comorbidities including bronchopulmonary dysplasia (OR 5.22, 2.01 - 13.53), prematurity (OR 3.10, 1.28 - 7.47), and autism (OR 3.69, 1.01 - 13.49) were associated with increased odds of PHTN. CONCLUSIONS: Significant echocardiographic evidence of PHTN was seen in 4.3% of children with OSA. ECHO findings of PHTN did not correlate with PSG parameters. Comorbidities, particularly bronchopulmonary dysplasia, prematurity, and autism, appear to be a risk factor for developing PHTN in patients with OSA.

Contemporary Outcomes in Fetuses Diagnosed with Vascular Rings.

Vascular rings are increasingly identified on fetal echocardiography. The purpose of this study is to analyze clinical outcomes and patterns of diagnostic testing in fetuses with vascular rings diagnosed by echocardiography. A retrospective cohort study was performed of fetuses with postnatally confirmed vascular rings from 2017 to 2022. Clinical outcomes included type and timing of symptoms, and timing of surgical intervention. Freedom from symptoms and/or surgery was assessed by Kaplan-Meier analysis. Frequency of genetic and diagnostic testing (barium esophagogram, CT/MRI angiogram, and bronchoscopy) was also assessed. Overall, 46 patients were evaluated (91% with a right aortic arch/left ductus and 4% with a double aortic arch). A vascular ring was isolated in 59%, associated with structural heart lesions in 33%, and associated with noncardiac anomalies in 8%. Prenatal diagnoses increased over time. Symptoms developed in 24% (11/46); 82% (9/11) had respiratory and 45% (5/11) had gastroesophageal complaints. Surgery was performed in 17% (11/46). Symptoms presented bimodally, prior to 100 or after 400 days of life. There was no difference in the type of symptoms for early (< 100 days) or late (> 400 days) presenters. Symptomatic patients received more diagnostic testing. Genetic testing was obtained in 46% and positive in 33%, with 22q11 deletion and Trisomy 21 being identified. Prenatal diagnoses of vascular rings increased over time, with subjects developing symptoms bimodally in early or late infancy. The frequency of genetic testing was suboptimal given the prevalence of genetic abnormalities seen in this population.

Inequalities in the dental health needs and access to dental services among looked after children in Scotland: a population data linkage study.

BACKGROUND: There is limited evidence on the health needs and service access among children and young people who are looked after by the state. The aim of this study was to compare dental treatment needs and access to dental services (as an exemplar of wider health and well-being concerns) among children and young people who are looked after with the general child population. METHODS: Population data linkage study utilising national datasets of social work referrals for 'looked after' placements, the Scottish census of children in local authority schools, and national health service's dental health and service datasets. RESULTS: 633 204 children in publicly funded schools in Scotland during the academic year 2011/2012, of whom 10 927 (1.7%) were known to be looked after during that or a previous year (from 2007-2008). The children in the looked after children (LAC) group were more likely to have urgent dental treatment need at 5 years of age: 23%vs10% (n=209/16533), adjusted (for age, sex and area socioeconomic deprivation) OR 2.65 (95% CI 2.30 to 3.05); were less likely to attend a dentist regularly: 51%vs63% (n=5519/388934), 0.55 (0.53 to 0.58) and more likely to have teeth extracted under general anaesthesia: 9%vs5% (n=967/30253), 1.91 (1.78 to 2.04). CONCLUSIONS: LAC are more likely to have dental treatment needs and less likely to access dental services even when accounting for sociodemographic factors. Greater efforts are required to integrate child social and healthcare for LAC and to develop preventive care pathways on entering and throughout their time in the care system.

Complete Depolymerization and Repolymerization of a Sugar Poly(orthoester).

The capability of a polymer to depolymerize, regenerating its original monomer for further polymerization, is very attractive in terms of sustainability. Recently discovered sugar poly(orthoesters) are an important class of glycopolymer. The high sensitivity of the backbone orthoester linkage toward acidolysis provides a valuable model to study the depolymerization. Herein, a sugar poly(orthoester) is shown to be completely depolymerized under acidic conditions. Interestingly, instead of the original monomer, the depolymerization gave a stable cyclic product (1,6-anhydro glucopyranose) in most cases, which was kinetically and thermodynamically favored. However, this pathway could be inhibited by chemically deactivating a key intermediate and thus favoring the formation of the original monomer. Efficient repolymerizaton of the regenerated monomer is also demonstrated.

Syntheses of sugar poly(orthoesters) through reverse anomeric effect.

High molecular weight sugar poly(orthoesters) were synthesized through reverse anomeric effect (RAE). We demonstrated that when RAE-enabled promoters, such as 4-(dimethylamino)pyridine (DMAP), triphenylphosphine (TPP) or imidazole, were employed, efficient polymerizations were achieved, giving sugar poly(orthoesters) with molecular weights up to 18 kDa.

Synthesis of clickable amphiphilic polysaccharides as nanoscopic assemblies.

The synthesis of clickable polysaccharides was achieved by using alkynylated 1,6-anhydro glucopyranose as a monomer and BF3·OEt2 as an effective catalyst. Subsequent click conjugation with polyethylene glycol (PEG) afforded PEG-grafted polysaccharides in nearly quantitative efficiency.

Synthesis of highly pH-responsive glucose poly(orthoester).

pH-Responsive polymers have great potential in biomedical applications, including the selective delivery of preloaded drugs to tissues with low pH values. These polymers usually contain acid-labile linkages such as esters and acetals/ketals. However, these linkages are only mildly pH-responsive with relatively long half-lives (t1/2 ). Orthoester linkages are more acid-labile, but current methods suffer from synthetic challenges and are limited to the availability of monomers. To address these limitations, a sugar poly(orthoester) was synthesized as a highly pH-responsive polymer. The synthesis was achieved by using 2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromide as a difunctional AB monomer and tetra-n-butylammonium iodide (TBAI) as an effective promoter. Under optimal conditions, polymers with molecular weights of 6.9 kDa were synthesized in a polycondensation manner. The synthesized glucose poly(orthoester), wherein all sugar units were connected through orthoester linkages, was highly pH-responsive with a half-life of 0.9, 0.6, and 0.2 hours at pH 6, 5, and 4, respectively.

Age impacts extracellular matrix metabolism in chondrocytes encapsulated in degradable hydrogels.

Encapsulation of autologous adult cartilage cells (chondrocytes) in hydrolytically degradable hydrogels may provide a clinically viable tissue engineering therapy for replacement of damaged or osteoarthritic cartilage. When designing a tissue engineering scaffold, it is crucial to evaluate adult chondrocytes due to their limited growth potential. The objective for this study was to compare extracellular matrix anabolic and catabolic metabolisms by juvenile and adult chondrocytes in hydrolytically degradable hydrogels. Cells were photo-encapsulated in bimodal degradable hydrogels composed of slow-degrading poly(ethylene glycol) (PEG) and the fast-degrading copolymer oligo(lactic acid)-b-PEG-b-oligo(lactic acid) crosslinks, and cultured through four weeks. Cell density was significantly higher in constructs containing adult cells, contributing to higher glycosaminoglycan content per wet weight. However, juvenile cells exhibited higher collagen content per cell. Immunohistochemical visualization revealed cartilage-specific aggrecan and collagen II deposition by both adult and juvenile cells. Immunohistochemically stained catabolically degraded collagen fragments and western blot-detected degraded aggrecan fragments, especially those associated with an osteoarthritic state, were more abundant in constructs with adult cells. Overall, bimodal degradable hydrogel environments were supportive of viable adult cells. However, major challenges with adult cells include their reduced collagen productivity and high catabolic activity, which may impact the quality of the engineered tissues.

Indoor localization using pedestrian dead reckoning updated with RFID-based fiducials.

We describe a low-cost wearable system that tracks the location of individuals indoors using commonly available inertial navigation sensors fused with radio frequency identification (RFID) tags placed around the smart environment. While conventional pedestrian dead reckoning (PDR) calculated with an inertial measurement unit (IMU) is susceptible to sensor drift inaccuracies, the proposed wearable prototype fuses the drift-sensitive IMU with a RFID tag reader. Passive RFID tags placed throughout the smart-building then act as fiducial markers that update the physical locations of each user, thereby correcting positional errors and sensor inaccuracy. Experimental measurements taken for a 55 m × 20 m 2D floor space indicate an over 1200% improvement in average error rate of the proposed RFID-fused system over dead reckoning alone.