Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. STUDY DESIGN: This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18 months of age. RESULTS: Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48 hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P < .001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P < .001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P < .001). CONCLUSION: The present study shows the complementary utility of cUS in the first 48 hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

BACKGROUND: Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. METHODS: A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. RESULTS: Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. CONCLUSIONS: NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. IMPACT: This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

Interdisciplinary collaboration: Data scientists and radiologists.

Interdisciplinary collaboration has become sought after by most institutions and corporations over the past few decades. This type of collaboration has grown exponentially since the advent of the internet and the information age. With the wave of interest to develop machine learning for the interpretation of diagnostic images it has become necessary for data scientists and radiologists to communicate through interdisciplinary research and collaboration. Such communication requires careful navigation for productive and meaningful outcomes. This article seeks to offer an overview of some previous literature discussing the best practices when forming interdisciplinary collaborative teams, explore some of the communication similarities and differences between the radiologist and data scientist disciplines, share some examples where pitfalls have caused confusion or frustration and re-work, and also to convey that, through trust, listening skills and knowing one's limitations, much can be learned and accomplished when working together.

The role of artificial intelligence in clinical imaging and workflows.

Evidence-based medicine, outcomes management, and multidisciplinary systems are laying the foundation for radiology on the cusp of a new day. Environmental and operational forces coupled with technological advancements are redefining the veterinary radiologist of tomorrow. In the past several years, veterinary image volumes have exploded, and the scale of hardware and software required to support it seems boundless. The most dynamic trend within veterinary radiology is implementing digital information systems such as PACS, RIS, PIMS, and Voice Recognition systems. While the digitization of radiography imaging has significantly improved the workflow of the veterinary radiology assistant and radiologist, tedious, redundant tasks are abundant and mind-numbing. They can lead to errors with a significant impact on patient care.  Today, these boring and repetitious tasks continue to bog down patient throughput and workflow. Artificial intelligence, particularly machine learning, shows much promise to rocket the workflow and veterinary clinical imaging into a new day where the AI management of mundane tasks allows for efficiency so the radiologist can better concentrate on the quality of patient care. In this article, we briefly discuss the major subsets of artificial intelligence (AI) workflow for the radiologist and veterinary radiology assistant including image acquisition, segmentation and mensuration, rotation and hanging protocol, detection and prioritization, monitoring and registration of lesions, implementation of these subsets, and the ethics of utilizing AI in veterinary medicine.

Genome sequencing for detection of pathogenic deep intronic variation: A clinical case report illustrating opportunities and challenges.

Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7-year-old male with a similar presentation found by research-based quad genome sequencing to have two novel splicing variants in trans in JAM3, including one deep intronic variant (NM_032801.4: c.256+1260G>C) not detectable by standard exome sequencing. Targeted sequencing of RNA isolated from transformed lymphoblastoid cell lines confirmed that each of the two variants has a deleterious effect on JAM3 mRNA splicing. The role for genome sequencing as a clinical diagnostic test extends to those patients with phenotypes strongly suggestive of a specific Mendelian disorder, especially when the causal genetic variant(s) are not found by a more targeted approach. Barriers to diagnosis via identification of pathogenic deep intronic variation include lack of laboratory consensus regarding in silico splicing prediction tools and limited access to clinically validated confirmatory RNA experiments.

The Neonatal Neurological Examination: Improving Understanding and Performance.

The neonatal neurological examination is a cornerstone in the assessment of a neonate's neurological function. Although current neuroimaging and neurophysiology techniques have markedly improved our ability to assess and diagnose neurologic abnormalities, the clinical neurological examination remains highly informative, cost-effective, and time efficient. Early recognition of abnormal findings can prevent delays in diagnosis and implementation of beneficial therapies. The intent of this article is to improve the understanding and performance of the neonatal neurological examination. A standardized approach to neonatal neurological examination is described, including examination techniques and normal and abnormal findings.

Intraventricular Hemorrhage and Posthemorrhagic Ventricular Dilation: Current Approaches to Improve Outcomes.

Intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD) are important complications of prematurity with short- and long-term implications for the patient and for nursing care. Several approaches have been shown to reduce the incidence of IVH and, more recently, mitigate the impact of IVH on long-term neurodevelopment. This article discusses the pathophysiology of IVH, with a focus on prevention strategies. Posthemorrhagic ventricular dilation is a common complication of severe IVH and has implications for neurodevelopmental sequelae. Both surgical and nonsurgical interventions for PHVD are described.

Sex differences in binge-like EtOH drinking, corticotropin-releasing hormone and corticosterone: effects of ß-endorphin.

Binge drinking is an increasingly common pattern of risky use associated with numerous health problems, including alcohol use disorders. Because low basal plasma levels of ß-endorphin (ß-E) and an increased ß-E response to alcohol are evident in genetically at-risk human populations, this peptide is thought to contribute to the susceptibility for disordered drinking. Animal models suggest that the effect of ß-E on consumption may be sex-dependent. Here, we studied binge-like EtOH consumption in transgenic mice possessing varying levels of ß-E: wild-type controls with 100% of the peptide (ß-E +/+), heterozygous mice constitutively modified to possess 50% of wild-type levels (ß-E +/-) and mice entirely lacking the capacity to synthesize ß-E (-/-). These three genotypes and both sexes were evaluated in a 4-day, two-bottle choice, drinking in the dark paradigm with limited access to 20% EtOH. ß-E deficiency determined sexually divergent patterns of drinking in that ß-E -/- female mice drank more than their wild-type counterparts, an effect not observed in male mice. ß-E -/- female mice also displayed elevated basal anxiety, plasma corticosterone and corticotropin-releasing hormone mRNA in the extended amygdala, and all of these were normalized by EtOH self-administration. These data suggest that a heightened risk for excessive EtOH consumption in female mice is related to the drug's ability to ameliorate an overactive anxiety/stress-like state. Taken together, our study highlights a critical impact of sex on neuropeptide regulation of EtOH consumption.

Prospective cohort study for identification of underlying genetic causes in neonatal encephalopathy using whole-exome sequencing.

PurposeNeonatal encephalopathy, which is characterized by a decreased level of consciousness, occurs in 1-7/1,000 live-term births. In more than half of term newborns, there is no identifiable etiological factor. To identify underlying genetic defects, we applied whole-exome sequencing (WES) in term newborns with neonatal encephalopathy as a prospective cohort study.MethodsTerm newborns with neonatal encephalopathy and no history of perinatal asphyxia were included. WES was performed using patient and both parents' DNA.ResultsNineteen patients fulfilling inclusion criteria were enrolled. Five patients were excluded owing to withdrawal of consent, no parental DNA samples, or a genetic diagnosis prior to WES. Fourteen patients underwent WES. We confirmed a genetic diagnosis in five patients (36%): epileptic encephalopathy associated with autosomal dominant de novo variants in SCN2A (p.Met1545Val), KCNQ2 (p.Asp212Tyr), and GNAO1 (p.Gly40Arg); lipoic acid synthetase deficiency due to compound heterozygous variants in LIAS (p.Ala253Pro and p.His236Gln); and encephalopathy associated with an X-linked variant in CUL4B (p.Asn211Ser).ConclusionWES is helpful at arriving genetic diagnoses in neonatal encephalopathy and/or seizures and brain damage. It will increase our understanding and probably enable us to develop targeted neuroprotective treatment strategies.

Effects of an entertaining, culturally targeted narrative and an appealing expert interview on the colorectal screening intentions of African American women.

Universal screening for colorectal cancer (CRC) is recommended for individuals 50-75 years of age, but screening uptake is suboptimal and African Americans have suffered persistent racial disparities in CRC incidence and deaths. We compared a culturally tailored fictional narrative and an engaging expert interview on the ability to increase intentions to be screened for CRC among African American women. In a post-only experiment, women (N = 442) in face-to-face listening groups in African American churches heard audio recordings of either a narrative or an expert interview. Questionnaires were completed immediately afterward and 30 days later. Women who heard narratives reported stronger intentions to be screened with a home stool blood test than women who heard the interview; the effect lasted at least 30 days. Culturally tailored, fictional narratives appear to be an effective persuasive strategy for reducing racial disparities in CRC outcomes.

Evaluation of Situation, Background, Assessment, Recommendation Tool During Neonatal and Pediatric Interfacility Transport.

OBJECTIVE: We aimed to determine if the implementation of Situation, Background, Assessment, Recommendation (SBAR) training improved the quality of real-life telephone communication. We evaluated interfacility neonatal and pediatric transports performed by registered nurses, respiratory therapists, and physicians (MDs). METHODS: This was a quality improvement study performed to evaluate telephone communication before and after SBAR training. Training consisted of lectures, review of audio files, and simulated role-playing. Recorded audio files of real-life transports were evaluated for clarity and content by 3 raters using a standardized scoring tool. RESULTS: Ninety-four and ninety-three calls were evaluated before and after the intervention, respectively. The total item scores were higher posttraining (mean ± standard deviation [pre: 15.06 ± 2.60, post: 17.60 ± 2.61], P < .001). Global rating scores ≥ 4 were higher in the posttraining group (pre: 50.0% vs. post: 66.7%; P = .02; odds ratio = 1.43; 95% confidence interval, 1.04-1.97). There was no significant difference in the duration of calls (mean ± SD [pre: 9.29 ± 4.59 minutes, post: 9.70 ± 4.65 minutes). In subgroup analysis, the total item score was significantly improved posttraining for registered nurses and respiratory therapists but not MDs. CONCLUSION: Standardized SBAR training was effective in improving telephone communication by RNs and RTs. The inclusion of SBAR training routinely within the educational curriculum of transport programs can enhance communication.

Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.

Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme ß-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease.

The availability of allograft skin for large scale medical emergencies in the United States.

Mass injury events present a unique medical challenge. Effective communications and coordination of resources including trained personnel as well as supplies and equipment are critical in these emergent situations. In the U.S., the availability of allograft skin plays a lifesaving role in treatment of burn injuries. Maintaining an adequate and readily available supply of this precious resource is critical for treatment of multiple injuries in the event of a national emergency. Allograft skin has historically been a local resource but contraction and consolidation of tissue banks has given rise to a small number of more nationally focused skin suppliers. While distinctly separate and essentially competing entities, these organizations come together in times of crisis to serve patients in need. Emergency preparations must include the ability to monitor and coordinate the capabilities of these organizations to supply lifesaving tissue grafts in times of national and global disasters.

Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage.

OBJECTIVE: Intraventricular hemorrhage (IVH) is a common cause of preterm brain injury. Fresh parent's own milk (POM) contains pluripotent stem cells (SCs) that produce neuronal cells in-vitro. The permeable neonatal blood brain barrier potentially allows SC delivery. We performed the first prospective trial (clinicaltrials.gov NCT04225286) of feasibility of intranasal POM (IPOM) in preterm infants with IVH and described SC content of POM samples. STUDY DESIGN: 37 Infants (mean gestation 27.7 ± 2.6 weeks, birthweight 1030 ± 320 g) with IVH (35.1% grade IV) were recruited from two tertiary Toronto NICUs. IPOM was given ideally twice daily until 28 days of age. Tolerance and adverse reactions were collected and 162 administering providers surveyed. RESULTS: There were no major adverse reactions. Provider surveys suggested acceptability, although potential provider and subject stress requires further study. Milk cell analysis suggests wide variability between parents. CONCLUSIONS: This phase 1 study demonstrated IPOM was tolerated and feasible in preterm infants.

Online vs in-person musculoskeletal ultrasound course: a cohort comparison study.

BACKGROUND: Point-of-care musculoskeletal (MSK) ultrasound (US) courses are typically held in-person. The COVID-19 pandemic guidelines forced courses to switch to online delivery. To determine this impact, we conducted an observational cohort study, comparing homework completion and image quality between an Online and a historical In-person cohort. METHODS: The In-person (n = 27) and Online (n = 24) cohorts attended two learning sessions spaced six months apart. The course content was the same, while the process of delivery differed. As homework, participants submitted US images biweekly for up to five months after each session. Expert faculty provided written feedback to all participants, and two independent reviewers rated the image quality for a subset of participants in each group who had completed at least 70% of their homework (In-person, n = 9; Online, n = 9). Participants self-reported their satisfaction through post-course evaluation. RESULTS: 63% of In-Person and 71% of Online cohort participants submitted their homework images. We observed no differences in the mean amount of homework images submitted for In-person (M = 37.3%, SD = 42.6%) and Online cohorts (M = 48.1%, SD = 38.8%; p > 0.05, Mann-Whitney U Test). At course end, the cohorts did not differ in overall image quality (p > 0.05, Wilcoxon Signed-rank Test). All participants reported high levels of satisfaction. CONCLUSIONS: A convenience sample of participants attending a basic MSK US course in-person and online did not differ statistically in homework completion, quality of submitted US images, or course satisfaction. We add to literature suggesting online learning remains a viable option post-pandemic.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Fruit and vegetable intake among rural youth following a school-based randomized controlled trial.

OBJECTIVE: We implemented a theory-based randomized controlled trial (Living Free of Tobacco, Plus (LIFT+) in ten rural middle schools and assessed impact on tobacco use and fruit/vegetable (F/V) intake in 2008-2010. Data on F/V intake at baseline, immediate post intervention, and 1-year follow-up are presented. METHODS: Schools were randomized to intervention or control groups. Goal setting, peer leaders, and class workshops with parent involvement, were intervention features; community partners were supportive. Seventh graders filled out surveys on health behaviors, psycho-social variables, and demographic characteristics. Adjusted models comparing intervention and control conditions were analyzed. RESULTS: Sample (n=1119) was 48.5% female, 50% White, with a mean age of 12.7 years. Mean F/V servings were significantly higher in intervention schools at immediate post (3.19 servings) and at 1-year (3.02 servings) compared to controls (2.90, 2.69 respectively). Knowledge of 5-a-day recommendation was significantly higher in intervention schools at immediate post test (75.0%) versus controls (53.8%) but not at 1-year follow-up. CONCLUSIONS: Intervention schools reported significantly higher mean F/V servings at post intervention and 1-year, and for knowledge of F/V recommendations at immediate post compared to controls. Higher levels of parent and community involvement may further increase F/V intake in future interventions. ClinicalTrials.gov Identifier: NCT01412697.