Outpatient clinical care for bronchopulmonary dysplasia: A survey of the BPD collaborative.

BACKGROUND: Bronchopulmonary dysplasia, a sequela of preterm birth, is the most common chronic respiratory disorder in infancy, and the second most common in children. Despite this, clinical care remains highly variable with guidelines supported by limited evidence, and do not provide specific guidance for timing of clinical follow-up, echocardiography, modalities of pulmonary function testing, etc. OBJECTIVE/METHODS: To further our understanding of care delivery for BPD, we sought to describe outpatient care patterns at tertiary care centers through survey data from 27 well-established BPD programs. RESULTS: We observed variability in referral patterns to outpatient BPD clinics, ancillary services provided, indications for follow-up echocardiograms, availability of lung function testing, and criteria for discharge from care. CONCLUSION: More comprehensive and detailed clinical guidelines similar to other pulmonary diseases such as asthma and cystic fibrosis should be developed to help standardize care and may improve long term outcomes.

A systematic review of epidemiological modelling in response to lumpy skin disease outbreaks.

Lumpy skin disease (LSD) is an infectious disease currently spreading worldwide and poses a serious global threat. However, there is limited evidence and understanding to support the use of models to inform decision-making in LSD outbreak responses. This review aimed to identify modelling approaches that can be used before and during an outbreak of LSD, examining their characteristics and priorities, and proposing a structured workflow. We conducted a systematic review and identified 60 relevant publications on LSD outbreak modelling. The review identified six categories of question to be addressed following outbreak detection (origin, entry pathway, outbreak severity, risk factors, spread, and effectiveness of control measures), and five analytical techniques used to address them (descriptive epidemiology, risk factor analysis, spatiotemporal analysis, dynamic transmission modelling, and simulation modelling). We evaluated the questions each analytical technique can address, along with their data requirements and limitations, and accordingly assigned priorities to the modelling. Based on this, we propose a structured workflow for modelling during an LSD outbreak. Additionally, we emphasise the importance of pre-outbreak preparation and continuous updating of modelling post-outbreak for effective decision-making. This study also discusses the inherent limitations and uncertainties in the identified modelling approaches. To support this workflow, high-quality data must be collected in standardised formats, and efforts should be made to reduce inherent uncertainties of the models. The suggested modelling workflow can be used as a process to support rapid response for countries facing their first LSD occurrence and can be adapted to other transboundary diseases.

Medical and social factors associated with prolonged length of stay for chronically ventilated children.

OBJECTIVES: This study seeks to determine the overall and post-intensive care unit (ICU) length of stay (LOS) for children with tracheostomies and chronic mechanical ventilation. We hypothesized that medical and social factors would be associated with prolonged LOS. STUDY DESIGN: This single-center retrospective review included children who were discharged after initiation of chronic ventilation via tracheostomy over an 8-year period (2015-2022). Patients were divided into two groups for analysis, those who had been previously home before admission (HBA) and those who had not (Not HBA). Medical and social determinants of health (SDOH) data were obtained from the electronic medical record for univariate and multivariable analyses. RESULTS: A total of 161 patients were included. HBA subjects (n = 52) were expectedly older at the time of tracheostomy. Not HBA subjects (n = 109) were more likely to be born prematurely and have sequelae of premature birth. Overall and post-ICU LOS increased for both groups during the study period. In the HBA subgroup, congenital heart disease and younger age were associated with longer overall LOS with these factors and the absence of gastric fundoplication being associated with longer post-ICU LOS. For Not HBA patients, younger age, pulmonary hypertension, seizures, and several SDOH were associated with longer overall LOS, whereas only SDOH were associated with a longer post-ICU LOS. CONCLUSIONS: Overall and post-ICU LOS for all children hospitalized for tracheostomy and chronic mechanical ventilation are increasing. Prolonged LOS is significantly associated with several medical factors and SDOH.

Simulation-Based Learning to Assess and Improve Critical Care Transport Team Members' Knowledge of Pediatric Intubation: A Quality Improvement Project.

OBJECTIVE: The care of critically ill neonatal and pediatric patients requiring transport is optimized by using specialty transport teams. Research demonstrates that training is best accomplished through routine simulation. At the project site, no simulation-based learning is provided to critical care transport team members. This project aimed to implement a simulation-based learning program to improve the knowledge and self-competency of neonatal and pediatric critical care transport team members. METHODS: Team members participated in two 9-week paired pediatric simulations that incorporated intubation and mechanical ventilation. Testing was conducted through a knowledge test and self-competency survey completed before and after both simulations and a performance checklist for each simulation. RESULTS: There was a statistically significant increase in knowledge test scores from the baseline knowledge test to each subsequent test (P ≤ .001, P = .002, and P ≤ .001). For self-competency, there was a statistically significant increase from the first survey to the second (P ≤ 0.001) and fourth (P ≤ .001). From the first to the second simulation, there was a statistically significant increase in performance (P ≤ .001). CONCLUSION: Paired simulation-based learning allows for the assessment and improvement of team members' knowledge. Future research should focus on how this improved knowledge translates to patient care.

Engineering error correcting dynamics in nanomechanical systems.

Nanomechanical oscillators are an alternative platform for computation in harsh environments. However, external perturbations arising from such environments may hinder information processing by introducing errors into the computing system. Here, we simulate the dynamics of three coupled Duffing oscillators whose multiple equilibrium states can be used for information processing and storage. Our analysis reveals that, within experimentally relevant parameters, error correcting dynamics can emerge, wherein the system's state is robust against random external impulses. We find that oscillators in this configuration have several surprising and attractive features, including dynamic isolation of resonators exposed to extreme impulses and the ability to correct simultaneous errors.

External validation of the BE-ALIVE score for predicting 30-day mortality in patients presenting with acute coronary syndromes.

INTRODUCTION: The BE-ALIVE score is an additive scoring system for estimating 30-day mortality in patients presenting with an acute coronary syndrome (ACS) [1]. However, it had only previously been tested on an internal validation cohort. The aim was to assess the scoring system on an external validation cohort. METHODS: The scoring system comprises six domains: (1) Base Excess (1 point for < -2 mmols/L), (2) Age (<65 years: 0 points, 65-74: 1 point, 75-84: 2 points, ≥ 85: 3 points), (3) Lactate (<2 mmols/L: 0 points, 2-4.9: 1 point, 5-9.9: 3 points, ≥ 10: 6 points), (4) Intubated & Ventilated (2 points), (5) Left Ventricular function (normal or mildly impaired: -1 point, moderately impaired: 1 point, severely impaired: 3 points) and (6) External / out of hospital cardiac arrest (1 point). We applied the BE-ALIVE score was applied to 205 consecutive patients at a different institution. RESULTS: Calibration was strong, with an observed to expected ratio of 1.01, a calibration slope of 1.26 and calibration in the large of -0.03. The Spiegelhalter's Z-statistic was -0.95 (p = 0.34). The AUC was 0.95 (0.92-0.98) in the external validation cohort versus 0.90 (0.85-0.95) during internal validation. Overall performance was excellent with a Brier score of 0.07 versus 0.06 during internal validation. The negative predictive value for 30-day mortality of a BE-ALIVE score < 4 was 98 %, with a positive predicted value of a score ≥ 10 of 95 %. CONCLUSIONS: The BE-ALIVE score remains a robust predictor of 30-day mortality in an external validation cohort.

Enhlink infers distal and context-specific enhancer-promoter linkages.

Enhlink is a computational tool for scATAC-seq data analysis, facilitating precise interrogation of enhancer function at the single-cell level. It employs an ensemble approach incorporating technical and biological covariates to infer condition-specific regulatory DNA linkages. Enhlink can integrate multi-omic data for enhanced specificity, when available. Evaluation with simulated and real data, including multi-omic datasets from the mouse striatum and novel promoter capture Hi-C data, demonstrate that Enhlink outperfoms alternative methods. Coupled with eQTL analysis, it identified a putative super-enhancer in striatal neurons. Overall, Enhlink offers accuracy, power, and potential for revealing novel biological insights in gene regulation.

Influenza and COVID-19 Vaccination Rates Among Children Receiving Long-Term Ventilation.

This cohort study examines rates of vaccination for COVID-19 and for influenza among children receiving long-term home ventilation.

Parental Report of Indoor Air Pollution Is Associated with Respiratory Morbidities in Bronchopulmonary Dysplasia.

OBJECTIVE: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative. STUDY DESIGN: A cross-sectional study was performed among participants <3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks. RESULTS: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, 1.24-3.84) were significantly higher in participants reporting exposure to secondhand smoke (SHS) compared with those without SHS exposure. Participants reporting exposure to air pollution (not including SHS) also had a significantly greater odds (OR, 1.48; 95% CI, 1.08-2.03) of antibiotic use as well. Indoor air pollution exposure (including SHS) was not associated with chronic respiratory symptoms or rescue medication use. CONCLUSIONS: Exposure to indoor air pollution, especially SHS, was associated with acute respiratory morbidities, including emergency department visits, antibiotics for respiratory illnesses, and systemic steroid use.

Outcomes of infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension who required home ventilation.

BACKGROUND: To characterize a cohort of ventilator-dependent infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) and to describe their cardiorespiratory outcomes. METHODS: Subjects with BPD on chronic home ventilation were recruited from outpatient clinics. PH was defined by its presence on ≥1 cardiac catheterization or echocardiogram on or after 36 weeks post-menstrual age. Kaplan-Meier analysis was used to compare the timing of key events. RESULTS: Of the 154 subjects, 93 (60.4%) had PH and of those, 52 (55.9%) required PH-specific medications. The ages at tracheostomy, transition to home ventilator, and hospital discharge were older in those with PH. Most subjects were weaned off oxygen and liberated from the ventilator by 5 years of age, which did not occur later in subjects with PH. The mortality rate after initial discharge was 2.6%. CONCLUSIONS: The majority of infants with BPD-PH receiving chronic invasive ventilation at home survived after initial discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen and PH medications, ventilator liberation, and tracheostomy decannulation. While the presence of PH was not associated with later ventilator liberation or decannulation, the use of PH medications may be a marker of a more protracted disease trajectory. IMPACT STATEMENT: There is limited data on long-term outcomes of children with bronchopulmonary dysplasia (BPD) who receive chronic invasive ventilation at home, and no data on those with the comorbidity of pulmonary hypertension (PH). Almost all subjects with BPD-PH who were on chronic invasive ventilation at home survived after their initial hospital discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen, PH medications, liberation from the ventilator, and tracheostomy decannulation. The presence of PH did not result in later ventilator liberation or decannulation; however, the use of outpatient PH medications was associated with later ventilation liberation and decannulation.

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro, facilitating the identification of kinase vulnerabilities to target therapeutically. The Kinase Chemogenomic Set is a well-annotated library of 187 kinase inhibitor compounds that indexes 215 kinases of the 518 in the known human kinome representing various kinase networks and signaling pathways, several of which are understudied. Our screen revealed 14 kinase inhibitor compounds effectively inhibited TNBC cell growth and proliferation. Upon further testing, three compounds, THZ531, THZ1, and PFE-PKIS 29, had the most significant and consistent effects across a range of TNBC cell lines. These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.

Factors associated with liberation from home mechanical ventilation and tracheostomy decannulation in infants and children with severe bronchopulmonary dysplasia.

OBJECTIVE: To identify factors associated with the timing of ventilator liberation and tracheostomy decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who required chronic outpatient invasive ventilation. STUDY DESIGN: Multicenter retrospective study of 154 infants with sBPD on outpatient ventilators. Factors associated with ventilator liberation and decannulation were identified using Cox regression models and multilevel survival models. RESULTS: Ventilation liberation and decannulation occurred at median ages of 27 and 49 months, respectively. Older age at transition to a portable ventilator and at discharge, higher positive end expiratory pressure, and multiple respiratory readmissions were associated with delayed ventilator liberation. Surgical management of gastroesophageal reflux was associated with later decannulation. CONCLUSIONS: Ventilator liberation timing was impacted by longer initial admissions and higher ventilator pressure support needs, whereas decannulation timing was associated with more aggressive reflux management. Variation in the timing of events was primarily due to individual-level factors, rather than center-level factors.

Interdisciplinary clinical bronchopulmonary dysplasia programs: development, evolution, and maturation.

Multidisciplinary bronchopulmonary dysplasia (BPD) programs provide improved and consistent medical management, care of the developing infant, family support, and smoother transitions in care resulting in improved survival, pulmonary, and extra-pulmonary outcomes. This review summarizes the benefits of interdisciplinary BPD management, as well as strategies for initial programmatic development, program growth, and maintenance at centers across the United States factoring in institutional, provider, and parent reported goals that were derived from a consensus conference on BPD management.

Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease, associated with premature birth, that arises during the infantile period. It is an evolving disease process with an unchanged incidence due to advancements in neonatal care which allow for the survival of premature infants of lower gestational ages and birth weights. Currently, there are few effective interventions to prevent BPD. However, careful attention to BPD phenotypes and comprehensive care provided by an interdisciplinary team have improved care. Interventions early in the disease course hold promise for improving long-term survival and outcomes in adulthood for this high-risk population.

A causal link between autoantibodies and neurological symptoms in long COVID.

Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.

Real-time imaging of axonal membrane protein life cycles.

The construction of neuronal membranes is a dynamic process involving the biogenesis, vesicular packaging, transport, insertion and recycling of membrane proteins. Optical imaging is well suited for the study of protein spatial organization and transport. However, various shortcomings of existing imaging techniques have prevented the study of specific types of proteins and cellular processes. Here we describe strategies for protein tagging and labeling, cell culture and microscopy that enable the real-time imaging of axonal membrane protein trafficking and subcellular distribution as they progress through some stages of their life cycle. First, we describe a process for engineering membrane proteins with extracellular self-labeling tags (either HaloTag or SNAPTag), which can be labeled with fluorescent ligands of various colors and cell permeability, providing flexibility for investigating the trafficking and spatiotemporal regulation of multiple membrane proteins in neuronal compartments. Next, we detail the dissection, transfection and culture of dorsal root ganglion sensory neurons in microfluidic chambers, which physically compartmentalizes cell bodies and distal axons. Finally, we describe four labeling and imaging procedures that utilize these enzymatically tagged proteins, flexible fluorescent labels and compartmentalized neuronal cultures to study axonal membrane protein anterograde and retrograde transport, the cotransport of multiple proteins, protein subcellular localization, exocytosis and endocytosis. Additionally, we generated open-source software for analyzing the imaging data in a high throughput manner. The experimental and analysis workflows provide an approach for studying the dynamics of neuronal membrane protein homeostasis, addressing longstanding challenges in this area. The protocol requires 5-7 days and expertise in cell culture and microscopy.

Symptomatic Calcified Uterine Fibroids Refractory to Repeat Uterine Artery Embolization: A Case Report.

Uterine leiomyomas, also known as uterine fibroids, are a commonly encountered condition with a diverse clinical presentation. Uterine fibroids are benign, smooth muscle tumors of the uterus arising from a single myometrial cell. The presentation can vary from asymptomatic incidental findings to causing a wide array of gynecological symptoms, including abnormal uterine bleeding, infertility, chronic pelvic pain, and bulk-related symptoms. There are several management approaches depending on the patient's clinical manifestations and goals. This is a unique case of a patient with symptomatic calcified uterine fibroids refractory to medical management and two uterine artery embolizations presenting with persistent abnormal uterine bleeding and chronic pelvic pain. Preservation of the uterus was desired, so an open myomectomy was subsequently performed. The patient was asymptomatic at two weeks follow-up, and further follow-up was unable to be obtained.  When considering interventions for symptomatic uterine fibroids, it is essential to consider the patient's preference for uterine-sparing methods and desire to preserve fertility. It is necessary that all modes of treatment and their potential future implications be discussed so that patients can make well-informed decisions regarding all aspects of their care. Further studies are needed comparing the outcomes of uterine-sparing interventions for symptomatic uterine fibroids so that the best possible shared decision-making can take place.

Adaptive sampling method to monitor low-risk pathways with limited surveillance resources.

The rise of globalization has led to a sharp increase in international trade with high volumes of containers, goods, and items moving across the world. Unfortunately, these trade pathways also facilitate the movement of unwanted pests, weeds, diseases, and pathogens. Each item could contain biosecurity risk material, but it is impractical to inspect every item. Instead, inspection efforts typically focus on high-risk items. However, low risk does not imply no risk. It is crucial to monitor the low-risk pathways to ensure that they are and remain low risk. To do so, many approaches would seek to estimate the risk to some precision, but increasingly lower risks require more samples. On a low-risk pathway that can be afforded only limited inspection resources, it makes more sense to assign fewer samples to the lower risk activities. We approach the problem by introducing two thresholds. Our method focuses on letting us know whether the risk is below certain thresholds, rather than estimating the risk precisely. This method also allows us to detect a significant change in risk. Our approach typically requires less sampling than previous methods, while still providing evidence to regulators to help them efficiently and effectively allocate inspection effort.

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age-appropriate tools. CONCLUSION: While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting.