Lung ultrasound to predict the duration of respiratory support in newborn infants with respiratory distress.

AIM: Lung ultrasound (LU) and clinical parameters evaluated during the first postnatal hour potentially predict the length of CPAP therapy in newborns with respiratory distress. METHODS: In a single-centre, prospective observational pilot study, 130 newborns ≥36 weeks gestational age were assessed using standardised LU at 30 and 60 min postnatally. Various clinical parameters were evaluated influencing CPAP duration (<1 vs. ≥1 h) using univariate and multivariate analyses. RESULTS: Lung ultrasound score >5, FiO2 > 0.21 and respiratory acidosis 30 min postnatally were associated with CPAP ≥1 h. Our model showed good diagnostic quality (ROC AUC = 0.87) and was confirmed by classification and regression tree (CART) analysis. Additional LU findings like double lung point and pleural line abnormalities were frequently observed, with good interrater reliability for LU interpretation (ICC = 0.76-0.77). CONCLUSION: Newborns with postnatal respiratory distress at risk for prolonged CPAP therapy can be identified based on specific LU and clinical parameters assessed 30 min postnatally. Despite the need for validation in an independent sample, these findings may lay the groundwork for a prediction tool. LU proved feasible and reliable for assessing respiratory status in this population, highlighting potential utility in clinical practice.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy.

PURPOSE: Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)-associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. METHODS: This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. RESULTS: All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. CONCLUSION: Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

Fractures of the proximal radius in children: management and results of 100 consecutive cases.

INTRODUCTION: Pediatric radial neck and head fractures are rare, accounting for only 1% of all fractures in children. The aim of this study is to describe the management and results of the respective fracture types and different injury characteristics. MATERIALS AND METHODS: This study performs a retrospective data analysis of 100 consecutive patients with a fracture of the proximal radius treated in a single high-volume pediatric trauma center. RESULTS: One hundred patients [mean age 7.5 years (1-15)] were documented with a fracture of the proximal radius between 3/2011 and 12/2019. The gender distribution was 62 girls and 38 boys. Twenty-seven patients had concomitant injuries. Conservative treatment was performed in 63 patients (Judet I = 27; II = 30; III = 6; Mason I = 2) using an above-the-elbow cast for 21 days (6-35). Surgical treatment was performed in 37 patients (Judet II = 3; III = 22; IV = 5; V = 7) using elastic stable intramedullary nailing (ESIN). Open reduction was necessary in five cases, and additional immobilization was performed in 32 cases. Six complications occurred: loss of implant stability (n = 2), healing in malalignment, pseudarthrosis, radioulnar synostosis, and a persisting hypoesthesia at the thumb. As a result, two ESIN osteosynthesis were revised, and one radial head resection was performed. Loss of movement was seen in 11% of cases, overall Mayo elbow performance index (MEPI) was 99.8 (90-100), and none of the patients experienced negative impacts on activities of daily life. CONCLUSIONS: Proximal radial fractures occur predominately without dislocation. Good results are obtained with conservative treatment throughout. In cases with displacement exceeding growth-related correction, ESIN is the undisputed treatment of choice. Open surgery and long immobilization periods should be avoided whenever possible.

Training in neonatal neurocritical care: a proposal for a hybrid model of competence by design and time-based methods.

BACKGROUND: Neonatal neurocritical care (NNCC) is a rapidly advancing field with limited fellowship training available in locally developed, non-accredited programs. A standardized survey aimed to understand the training backgrounds of individuals practicing NNCC, the structure of existing clinical NNCC services/training programs, and suggested clinical competencies for new graduates. METHODS: We developed an anonymous survey electronically sent to members of societies related to NNCC. Using the survey results as a guide, we discuss a competence by design (CBD) curriculum as a complementary approach to traditional time-based training. RESULTS: There were 82 responses to the survey from 30 countries; 95% of respondents were physicians. Thirty-one (42%) institutions reported having an NNCC service, 24 (29%) individuals reported formal NNCC training, 81% reported "significant variability" across NNCC training programs, and 88% were both in favor of standardizing training programs and pursuing formal accreditation for NNCC in the next 5 years. CONCLUSIONS: The survey results demonstrate international interest in standardizing NNCC training and development of an accreditation or certification process. We propose consideration of a CBD-type curriculum as a training approach to focus on the development of specific NNCC competencies, rather than assuming the acquisition of these competencies based on time as a surrogate. IMPACT: Continued growth and development in the field of NNCC has led to increasing need for training programs suited to meet the diverse needs of trainees from varied backgrounds. We present the results of an international survey that assessed the structure of existing training programs and the priority areas in which graduates must demonstrate competence, highlighting the combination of CBD and time-based training as one approach to address these recommendations. The survey results support interest in translating published training competencies, existing expertise, and infrastructure across centers into a standardized curriculum for NNCC including certification opportunities.

Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters.

OBJECTIVE: To identify textural features on dual-energy CT (DECT)-based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement. METHODS: A total of 110 patients (63.0 ± 11.0 years, 51 female) who underwent unenhanced whole-body DECT between September 2015 and February 2019 were retrospectively included, which was approved by our institutional ethics committee with a waiver of the informed consent requirement. All patients had current hematologic laboratory tests. Using DECT post-processing, non-calcium bone marrow images were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of textural features, which were compared with serologic parameters and myeloma stages by the Mann-Whitney U test. In a subgroup of 56/110 patients with current bone marrow biopsies, textural features were correlated with the degree of bone marrow infiltration. RESULTS: First-order features were higher in patients with advanced stage of myeloma (p < .02), whereas the 2nd-order "gray-level co-occurrence matrix (GLCM) cluster prominence" was lower (p < .04). In patients with elevated serum-free light chains (SFLC) or kappa/lambda SFLC ratio above 1.56, the "entropy" and 2nd-order GLCM features were lower (p < .03). The degree of bone marrow infiltration correlated with 1st-order features (e.g., "uniformity"; rP = 0.49; p < .0001), whereas "entropy" and 2nd-order GLCM features were negatively correlated (e.g., "difference entropy"; rP = - 0.54; p < .0001). CONCLUSIONS: CT textural features applied on non-calcium bone marrow images correlate well with myeloma-related serologic parameters and histology showing a more uniform tissue structure and higher attenuation with increasing medullary infiltration and could therefore be used as additional imaging biomarkers for non-invasive assessment of medullary involvement. KEY POINTS: • Texture analysis applied on dual-energy reconstructed non-calcium bone marrow images provides information about marrow structure and attenuation. • Myeloma-related serologic parameters and the degree of myeloma cell infiltration correlate with 1st- and 2nd-order features which could be useful as additional imaging biomarkers for non-invasive assessment of medullary involvement.

Impact of outreach education program on outcomes of neonates with hypoxic ischemic encephalopathy.

AIM: To evaluate the impact of outreach education targeting neuroprotection on outcomes of outborn infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). METHODS: A retrospective cohort study of infants admitted with moderate-to-severe HIE was conducted following the implementation of outreach education in January 2016. Key interventions were early identification and referral of infants with encephalopathy utilizing telemedicine and a centralized communication system, hands-on simulation, and interactive case discussion and dissemination of clinical management guidelines and educational resources. The association between the intervention and a composite outcome of death and/or severe brain injury on brain magnetic resonance imaging (MRI) was tested controlling for the confounding factors. RESULTS: Of 165 neonates, 37 (22.4%) died and/or had a severe brain injury. This outcome decreased from 35% (27/77) to 11% (10/88) following the implementation of outreach education (P<0.001). Eligible infants not undergoing therapeutic hypothermia within 6 hours from birth decreased from 19.5% (15/77) to 4.5% (4/88). The use of inotropes decreased from 49.3% (38/77) to 19.6% (13/88). Any core temperature below 33°C was recorded for 20/53 (38%) before and 16/78 (21%) after, while those within the target range of 33°C to 34°C at admission to a tertiary care facility increased from (15/53) 28% to (51/88) 58%. Outreach education was independently associated with decreased composite outcome of death and/or severe brain injury on MRI (adjusted odds ratio 0.2; 95% confidence interval 0.07 to 0.52). CONCLUSION: Outreach education targeting neuroprotection for infants with moderate-to-severe HIE was associated with a reduction in death and/or severe brain injury.

Forensic age estimation in living adolescents with CT imaging of the clavicula-impact of low-dose scanning on readers' confidence.

OBJECTIVES: Computed tomography (CT) imaging of the clavicula displays the reference standard for forensic bone age diagnostics in adolescents and young adults. Consequently, highest efforts on radiation reduction are warranted. Therefore, the aim of this study was to investigate the feasibility of low-dose (LD) CT imaging of the clavicula for age estimation in living adolescents. METHODS: A total of 207 non-contrast chest CT of 144 patients born between 1988 and 2012, performed in 2018 due to various clinical indications, were included in this retrospective study. The mean patient age was 16.9 ± 6.6 years. Patients were divided into a LD (n = 146) and standard-dose (SD; n = 61) group. Image quality, confidence levels, and ossification stages (using the 5-stage classification including the subgroups 2a-3c) were assessed by two radiologists independently. Radiation dose was determined via dosimetry software. RESULTS: Dose simulation with z-axis reduction to depict the clavicula only resulted in a median exposure of 0.1 mSv (IQR: 0.0) in LD compared with 0.9 mSv (IQR: 0.6) in SD (p < 0.001). The median image quality was rated by both readers significantly worse in LD compared with SD on a Likert scale ranging from 1 to 4 with a median of 3 (IQR: 1) versus 4 (IQR: 0; p < 0.001 for both readers). There was an almost perfect agreement for the ossification stages between both readers with a Cohen's kappa of 0.83 (p < 0.001). Median confidence levels of both readers were not significantly different between LD and SD in the decisive subgroups 2a-3c. CONCLUSIONS: Low-dose CT imaging of the clavicula for age estimation in living adolescents is possible without loss of readers' confidence. KEY POINTS: • Radiological bone age diagnostics in young delinquents with unknown exact chronological age is important as the judicial systems differentiate between youths and adults. • Low-dose computed tomography scanning of the medial clavicular joint for forensic age estimation is feasible in living adolescents without loss of readers' confidence. • Sufficient image quality of the medial clavicular joint for forensic bone age diagnostics in living adolescents is achievable using a median dose of 0.1 mSv.

Functional magnetic resonance imaging study of working memory several years after pediatric concussion.

PRIMARY OBJECTIVE: The neurophysiological effects of pediatric concussion several years after injury remain inadequately characterized. The objective of this study was to determine if a history of concussion was associated with BOLD response differences during an n-back working memory task in youth. RESEARCH DESIGN: Observational, cross-sectional. METHODS AND PROCEDURES: Participants include 52 children and adolescents (M = 15.1 years, 95%CI = 14.4-15.8, range = 9-19) with past concussion (n = 33) or orthopedic injury (OI; n = 19). Mean time since injury was 2.5 years (95%CI = 2.0-3.0). Measures included postconcussion symptom ratings, neuropsychological testing, and blood-oxygen-dependent-level (BOLD) functional magnetic resonance imaging (fMRI) during an n-back working memory task. MAIN OUTCOMES AND RESULTS: Groups did not differ on accuracy or speed during the three n-back conditions. They also did not differ in BOLD signal change for the 1- vs. 0-back or 2- vs. 0-back contrasts (controlling for task performance). CONCLUSIONS: This study does not support group differences in BOLD response during an n-back working memory task in youth who are on average 2.5 years post-concussion. The findings are encouraging from the perspective of understanding recovery after pediatric concussion.

Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction.

The understanding of molecular biology in neurocritical care (NCC) is expanding rapidly and recognizing the important contribution of neuroinflammation, specifically changes in immunometabolism, towards pathological disease processes encountered across all illnesses in the NCC. Additionally, the importance of individualized inflammatory responses has been emphasized, acknowledging that not all individuals have the same mechanisms contributing towards their presentation. By understanding cellular processes that drive disease, we can make better personalized therapy decisions to improve patient outcomes. While the understanding of these cellular processes is evolving, the ability to measure such cellular responses at bedside to make acute care decisions is lacking. In this overview, we review cellular mechanisms involved in pathological neuroinflammation with a focus on immunometabolic dysfunction and review non-invasive bedside tools that have the potential to measure indirect and direct markers of shifts in cellular metabolism related to neuroinflammation. These tools include near-infrared spectroscopy, transcranial doppler, elastography, electroencephalography, magnetic resonance imaging and spectroscopy, and cytokine analysis. Additionally, we review the importance of genetic testing in providing information about unique metabolic profiles to guide individualized interpretation of bedside data. Together in tandem, these modalities have the potential to provide real time information and guide more informed treatment decisions.

Sex-dependent and chronic alterations in behavior and mitochondrial function in a rat model of pediatric mild traumatic brain injury.

OBJECTIVE: To determine if chronic changes in mitochondrial function occur following a mild traumatic brain injury in young rats. RESEARCH DESIGN: Closed-head, weight drop model was used to cause mTBI by applying rotational forces to the brain without surgery. Behavioral battery was used to assess multiple dimensions of impairment across time. Analysis of brain tissue carried out at three-weeks post-injury represents a chronic time point to complement previous work examining acute time points. METHODS AND PROCEDURES: Twenty-three male and 22 female rats one month of age were divided equally into sham and mTBI groups with the latter undergoing the weight drop. Multiple behavioral tests in combination with energetic (oxygen consumption), molecular (immunoblotting), and imaging (electron microscopy) characterization of brain mitochondria were performed. MAIN OUTCOMES AND RESULTS: Mitochondria isolated from sham juvenile female rats had higher basal oxygen consumption compared to juvenile male rats (514.875 ± 171.091 pmol/min vs. 267 ± 73.906 pmol/min, p < 0.0001). Chronic sex-dependent differences were observed in females after mTBI in basal (514.875 ± 171.091 pmol/min vs. 600.688 ± 124.422 pmol/min, p = 0.0264) and maximal oxygen consumption (298.938 ± 119.964 pmol/min vs. 403.281 ± 112.922 pmol/min, p = 0.0001) and proton leak (59.46 ± 7.807 vs. 84.32 ± 5.80 pmol/min, p = 0.0001). CONCLUSIONS: The juvenile rat brain displays sex differences in mitochondrial function at (1) baseline and (2) in long-term outcomes after mTBI. These results offer new insight into a potential mechanism for persistent, individualized impairments following pediatric mTBI.

Introduction of Continuous Video EEG Monitoring into 2 Different NICU Models by Training Neonatal Nurses.

BACKGROUND: Continuous video electroencephalographic (EEG) (cvEEG) monitoring is emerging as the standard of care for diagnosis and management of neonatal seizures. However, cvEEG is labor-intensive and the need to initiate and interpret studies on a 24-hour basis is a major limitation. PURPOSE: This study aims at establishing consistency in monitoring of newborns admitted to 2 different neonatal intensive care units (NICUs) managed by the same neurocritical care team. METHODS: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues, and identify amplitude-integrated EEG abnormalities. Guidelines, checklists, and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. A cohort of 100 infants with moderate to severe hypoxic-ischemic encephalopathy before and after the training program was compared. RESULTS: During the study period, 192 cvEEGs were obtained. The time to initiate brain monitoring decreased by 31.5 hours posttraining; this, in turn, led to an increase in electrographic seizure detection (20% before vs 34% after), decrease in seizure clinical misdiagnosis (65% before and 36% after), and reduction in antiseizure medication burden. IMPLICATIONS FOR PRACTICE: Training experienced NICU nurses to set up, start, and monitor cvEEGs can decrease the time to initiate cvEEGs, which may lead to better seizure diagnosis and management. IMPLICATIONS FOR RESEARCH: Further understanding of practice bundles for best supporting infants at risk and being treated for seizures needs to be evaluated for integration into practice.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Contrast-Enhanced High-Pitch Computed Tomography in Pediatric Patients Without Electrocardiography Triggering and Sedation: Comparison of Cardiac Image Quality With Conventional Multidetector Computed Tomography.

OBJECTIVE: The aim of this study was to compare image quality of anatomical cardiac details without electrocardiography triggering, sedation, or heart rate-regulating drugs in contrast-enhanced pediatric chest computed tomography (CT), using high-pitch CT (HPCT) versus conventional pitch-mode technique (multidetector CT [MDCT]). METHODS: After written informed consent, 55 patients (median age, 11 years; range, 3-17 years) were prospectively included in this institutional review board-approved study. Patients underwent clinically indicated, contrast-enhanced MDCT or HPCT of the chest.Image quality was assessed evaluating morphological criteria on a 3-point scale (from 1, high, to 3, low detail) and summed up in a global score (from 4, best, to 12, poor image quality). Artifacts were analyzed correspondingly (from 3, low, to 9, severe artifacts). Effective dose and size-specific dose estimate were calculated for all scans. RESULTS: Cardiac image quality was higher in HPCT than in MDCT (7.1 [1.6] vs 8.8 [1.9], P < 0.001). Nevertheless, HPCT showed limitations in image quality, especially concerning the heart valves (2.5 [0.6] and 1.7 [0.5]) and coronary arteries (1.8 [0.6). Artifact score (3.4 [0.6 vs 5.1 [0.9, P < 0.001), effective dose (1.6 [1.3] vs 2.3 [1.6] mSv, P = 0.047), and size-specific dose estimate (2.5 [1.7] vs 4.1 [2.3] mGy, P = 0.002) were lower in HPCT compared with those in MDCT. CONCLUSIONS: In pediatric patients, contrast-enhanced HPCT of the chest provides high image quality without electrocardiography triggering or sedation, although image quality is somewhat limited for a detailed depiction of cardiac anatomy.

Reducing the time interval between concussion and voluntary exercise restores motor impairment, short-term memory, and alterations to gene expression.

Despite the most common form of brain injury, there has been little progress in the prognosis and treatment of concussion/mild traumatic brain injury (mTBI). Current 'return-to-play' guidelines are conservative, deterring the initiation of physical and social activity until patients are asymptomatic; but the effects of post-injury exercise have not been adequately investigated. Therefore, this study examined the effects of voluntary exercise on concussion recovery. Using a translational rodent model of concussion, we examined the influence of exercise on injury-associated behaviours that comprise post-concussive syndrome (PCS) and gene expression changes (bdnf, dnmt1, Igf-1, pgc1-a, Tert) in prefrontal cortex and hippocampus. In addition, as we have previously demonstrated telomere length (TL) to be a reliable predictor of mTBI prognosis, TL was also examined. The results suggest that exercise initiated within 1-3 days post-concussion significantly improved motor and cognitive functioning, but had limited efficacy treating emotional impairments. What is more, when deprived of social interaction and exercise, a combination similar to clinical recommendations for rest until symptom resolution, animals did not recover and exhibited impairments similar to typical mTBI animals. Exercise aided in restoration of mTBI-induced modifications to gene expression in both brain regions. An inverse relationship between the exercise return interval and TL was identified, indicating greater recovery with acute exercise reinstatement. Although additional strategies may need to be employed for emotional functioning, these findings support re-evaluation of 'return-to-play' guidelines, suggesting that exercise is valuable for the treatment of concussion.

Complexity of Ultrasound and CT Fusion Examinations: Are They Feasible in the Daily Routine?

OBJECTIVE: The purpose of this study is to determine whether ultrasound and CT image fusion, used for the assessment of upper abdominal organ lesions, can be successfully managed in a passable examination time and whether the method is feasible in the clinical daily routine. SUBJECTS AND METHODS: Fifty-four consecutive patients presenting with organ lesions on contrast-enhanced CT underwent ultrasound and CT fusion imaging the same day. Examination times per patient, per organ, and per lesion were registered, and the mean diameter of all lesions per examination was calculated. Initial automatic superimposition was followed by manual superimposition using up to three landmarks. RESULTS: A total of 199 lesions (mean, 3.7 lesions per patient) were assessed. Thirty-three examiniations yielded benign results, and seven examinations revealed malignant findings. In 14 patients a coexistence of both benign and malignant lesions was found. The mean examination time per patient was 11.5 minutes, the time per organ was 6.8 minutes, and the time per lesion was 4 minutes. The required time per organ (p < 0.001) and per lesion (p = 0.62) decreased when more organs were evaluated. The expenditure of time was higher when only malignant lesions were detected, compared with explicitly benign lesions (9.7 vs 6.7 minutes per organ, p = 0.84; 4.9 vs 4.1 minutes per lesion, p = 0.56). Lesions smaller than 10 mm required a longer examination time compared with lesions 10 mm and larger (7.6 vs 6.3 minutes per organ, p = 0.79; 4.5 vs 3.6 minutes per lesion, p = 0.35). CONCLUSION: Ultrasound and CT fusion with the objective of lesion classification can be realized in an acceptable examination time and is recommended for elucidation of undetermined small lesions on contrast-enhanced CT, if they are not directly detected at unfused ultrasound.

Canadian Paediatric Neurology Workforce Survey and Consensus Statement.

BACKGROUND: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. METHODS: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. RESULTS: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. CONCLUSIONS: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.

Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats.

Mild traumatic brain injury (mTBI) or concussion affects a large portion of the population and although many of these individuals recover completely, a small subset of people experience lingering symptomology and poor outcomes. Little is known about the factors that affect individual susceptibility or resilience to poor outcomes after mTBI and there are currently no biomarkers to delineate mTBI diagnosis or prognosis. Based upon the growing literature associated with caloric intake and altered neurological aging and the ambiguous link between repetitive mTBI and progressive neurodegeneration, the current study was designed to examine the effect of a high fat diet (HFD), developmental age, and repetitive mTBI on behavioral outcomes following a mTBI. In addition, telomere length was examined before and after experimental mTBI. Sprague Dawley rats were maintained on a HFD or standard rat chow throughout life (including the prenatal period) and then experienced an mTBI/concussion at P30, P30 and P60, or only at P60. Behavioral outcomes were examined using a test battery that was administered between P61-P80 and included; beam-walking, open field, elevated plus maze, novel context mismatch, Morris water task, and forced swim task. Animals with a P30 mTBI often demonstrated lingering symptomology that was still present during testing at P80. Injuries at P30 and P60 rarely produced cumulative effects, and in some tests (i.e., beam walking), the first injury may have protected the brain from the second injury. Exposure to the high fat diet exacerbated many of the behavioral deficits associated with concussion. Finally, telomere length was shortened following mTBI and was influenced by the animal's dietary intake. Diet, age at the time of injury, and the number of prior concussion incidents differentially contribute to behavioral deficits and may help explain individual variations in susceptibility and resilience to poor outcomes following an mTBI.

Prognostic relevance of positive urine markers in patients with negative cystoscopy during surveillance of bladder cancer.

BACKGROUND: The role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. In case of negative cystoscopy the additional prognostic value of these markers has not been clearly defined yet. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC. METHODS: One hundred fourteen patients who underwent urine marker testing during surveillance for NMIBC and who had no evidence of BC recurrence were included. For all patients cytology, Fluorescence-in-situ-hybridization (FISH), immunocytology (uCyt+) and Nuclear matrix protein 22 enzyme-linked immunosorbent assay (NMP22) were performed. All patients completed at least 24 months of endoscopic and clinical follow-up of after inclusion. RESULTS: Within 24 months of follow-up, 38 (33.0%) patients experienced disease recurrence and 11 (9.8%) progression. Recurrence rates in patients with positive vs. negative cytology, FISH, uCyt+ and NMP22 were 52.6% vs. 21.9% (HR = 3.9; 95% CI 1.75-9.2; p < 0.001), 47.6% vs. 25.0% (HR 2.7; 1.2-6.2; p = 0.01), 43.8% vs. 22.4% (HR 3.3; 1.5-7.6; p = 0.003) and 43.8% vs. 16.7% (HR 4.2; 1.7-10.8; p = 0.001). In patients with negative cytology, a positive NMP22 test was associated with a shorter time to recurrence (p = 0.01), whereas FISH or uCyt+ were not predictive of recurrence in these patients. In the group of patients with negative cytology and negative NMP22, only 13.5% and 5.4% developed recurrence and progression after 24 months. CONCLUSIONS: Patients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.

An enhanced home cage modulates hypothalamic CRH-ir labeling in juvenile rats, with and without sub-threshold febrile convulsions.

Pre and postnatal environments can have a profound impact on offspring development. This is especially true when considering the origin of neurological diseases, including epilepsy, a relatively common and chronic neurological condition, affecting 1-2% of the population. Previously, we have used maternal stress and an enhanced home cage (EHC) in an effort to identify potential factors in the early environment that may increase the risk for experiencing seizures. First, pregnant Long-Evans rats were exposed to a predator stress (PS). Then, at birth, litters were divided into standard cage (SC) and EHC groups until postnatal Day 14 (PD14) when a model of febrile convulsions was used to determine convulsion susceptibility of the various groups. Twenty-four hours later, pup brains were processed for immunohistochemical detection of corticotrophic releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus. Analysis of CRH immunoreactive (-ir) patterns revealed a buffering of CRH-ir in EHC reared offspring. Further, experiencing convulsions led to decreased CRH-ir. Our results support the concept that postnatal environmental influences affect neonatal programming and neurodevelopment of processes that could underlie seizure susceptibility, and that these effects can be modulated by EHC conditions.

Feasibility and Implementation of a 4D Free-Breathing Variable Density Stack-of-Stars Functional Magnetic Resonance Urography in Young Children Without Sedation.

BACKGROUND: Functional magnetic resonance urography (MRU) is well established in the diagnostic workup of urinary tract anomalies in children, providing comprehensive morphological and functional information. However, dynamic contrast-enhanced images acquired in the standard Cartesian k-space manner are prone to motion artifacts. A newly introduced 4D high spatiotemporal resolution dynamic contrast-enhanced magnetic resonance imaging based on variable density elliptical centric radial stack-of-stars sharing technique has shown improved image quality regarding motions under free breathing. OBJECTIVE: The aims of this study were to implement this 4D free-breathing sequence for functional MRU and to compare its image quality and analyzability with standard breath-hold Cartesian MRU. MATERIALS AND METHODS: We retrospectively evaluated all functional 4D MRU performed without general anesthesia between September 2021 and December 2022 and compared them with matched pairs (age, affected kidney, diagnosis) of standard Cartesian MRU between 2016 and 2022. Image analysis was performed by 2 radiologists independently regarding the following criteria using a 4-point Likert scale, with 4 being the best: overall image quality, diagnostic confidence, respiratory motion artifacts, as well as sharpness and contrast of aorta, kidneys, and ureters. We also measured vertical kidney motion due to respiratory motion and compared the variance for each kidney using F test. Finally, both radiologists calculated the volume, split renal volume (vDRF), split renal Patlak function (pDRF), and split renal function considering the volume and Patlak function (vpDRF) for each kidney. Values were compared using Bland-Altman plots and F test. RESULTS: Forty children (20 for 4D free-breathing and standard breath-hold, respectively) were enrolled. Ten children of each group were examined using feed-and-sleep technique (median age: 4D, 3.3 months; standard, 4.2 months), 10 were awake (median age: 4D, 8.9 years; standard, 8.6 years). Overall image quality, diagnostic confidence, respiratory motion artifacts, as well as sharpness and contrast of the aorta, kidneys, and ureters were rated significantly better for 4D free-breathing compared with standard breath-hold by both readers ( P ranging from <0.0001 to 0.005). Vertical kidney motion was significantly reduced in 4D free-breathing for the right and the left kidney (both P < 0.001). There was a significantly smaller variance concerning the differences between the 2 readers for vpDRF in 4D MRU ( P = 0.0003). In contrast, no significant difference could be demonstrated for volume ( P = 0.05), vDRF ( P = 0.93), and pDRF ( P = 0.14). CONCLUSIONS: We demonstrated the feasibility of applying a 4D free-breathing variable density stack-of-stars imaging for functional MRU in young pediatric patients with improved image quality, fewer motion artifacts, and improved functional analyzability.