Sleep disorders in pediatric patients with agenesis of the corpus callosum.

STUDY OBJECTIVES: There is limited information about sleep in agenesis of the corpus callosum (ACC). We aim to describe the sleep architecture and respiratory parameters of children with ACC. METHODS: We performed a retrospective study of 20 patients with ACC who had polysomnography (PSG) between 2000-2023. Demographic data, BMI or weight for length, associated conditions, and PSG findings were collected. National Sleep Foundation (NSF) sleep quality indicators as well as increased PSG arousal index ≥10/h were used in the analysis. Fisher's exact test or unpaired t-test was used to compare groups. RESULTS: Average age was 5.9 ± 5.4 years old; 12/20 patients were male. 6/20 were overweight/obese. 14/20 had complete ACC, and 6/20 had partial ACC. 8/20 had seizures. 15/20 had ≥1 NSF poor sleep quality indicator (decreased SE (45%), decreased REM (53%)) and 9/20 had increased arousals. Between complete and partial ACC, there was no difference in presence of ≥1 poor sleep quality indicator (p= 0.61), SE (p=0.34), REM (p=0.28), and arousals (p=1.0). 11/18 had obstructive sleep apnea (OSA); 5/11 had associated central sleep apnea. There was no difference in OSA between those with complete and partial ACC (p=1.0). OSA was associated with children <3 years old (p=0.01). CONCLUSIONS: Children with ACC have poor sleep quality, and many have OSA. There was no difference in sleep quality or presence of OSA between those with complete and partial ACC. OSA was seen more in younger children. Our study supports the need for screening of sleep-related disorders in patients with ACC.

Obstructive sleep apnea as a presentation of congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome is a rare disorder due to a mutation in the PHOX2B gene, characterized by a failure in autonomic control of breathing with diminished or absent response to hypoxia and hypercapnia, which is most pronounced during sleep. Most patients present from birth with central apneas and hypoventilation, or later in the setting of a physiologic stress. Recent literature in mice with a Phox2b27Ala/+ mutation suggests a predisposition to obstructive apneas likely due to hypoglossal dysgenesis. We report on three patients with obstructive sleep apneas with absent or mild hypoventilation. Our cases propose that obstructive apneas can be the primary presentation in patients who subsequently develop the classic phenotype of congenital central hypoventilation syndrome and emphasize their close monitoring and surveillance. CITATION: Kagan O, Zhang C, McElyea C, Keens TG, Davidson Ward SL, Perez IA. Obstructive sleep apnea as a presentation of congenital central hypoventilation syndrome. J Clin Sleep Med. 2023;19(9):1697-1700.

Impact of Blockchain-Digital Twin Technology on Precision Health, Pharmaceutical Industry, and Life Sciences: Conference Proceedings, Conv2X 2023.

The convergence of Digital Twin technologies with precision health, the pharmaceutical industry, and life sciences has garnered substantial recent attention. As we advance toward personalized medicine and precision health, the fusion of Digital Twin and blockchain technologies is poised to enhance healthcare outcomes fundamentally. This conference discussion highlighted pivotal drivers accelerating the adoption of Digital Twin-enabled blockchain solutions, encompassing the shift to a decentralized World Wide Web (Web 3.0), the establishment of a global interconnected health ecosystem, and the distinct advantages offered by converging frontier technologies in optimizing healthcare, pharmaceutical industry, and life sciences. Yet, the effective deployment of blockchain-powered Digital Twins in precision health necessitates robust cyber safety measures, proactive ethical frameworks, data validation, provenance assurance, streamlined supply chain management, and heightened interoperability. These proceedings underscored blockchain-powered Digital Twins' pivotal role in reshaping health data management, security, sharing, ownership, and monetization and in revolutionizing pharmaceutical supply chain management and novel drugs and therapeutics development within the precision health domain.

Rates of diagnoses of sleep disorders in children with chronic medical conditions.

STUDY OBJECTIVES: This investigation examines sleep disorder (SD) diagnoses in a large population of children and adolescents with chronic medical conditions (CMCs). Little is known about SD diagnoses in this population. The large population used in this study allowed examination of SD rates by CMC type and demographics. METHODS: Data were from the Coordinated Health Care for Complex Kids (CHECK) project designed for Medicaid-funded children and adolescents with at least 1 CMC from a large metropolitan area. The study population (n = 16,609) was limited to children and adolescents, 0 to 18 years of age. SD and CMC diagnoses were obtained from Medicaid claims data. RESULTS: Fourteen percent of the population (mean age of 9.1 years [standard deviation = 5.2]; 35.8% African American; 56.4% male; 77 with more than 1 CMC) received a sleep disorder diagnosis. The most frequent diagnosis was sleep-disordered breathing (11.2%), followed by nocturnal enuresis (1.2%) and insomnia (1%). SDs were diagnosed more frequently in those with multiple CMCs than in those with 1 CMC (19.7% vs 5.8%; P < .001). Insomnia rates in Hispanic/Latinx (1.2%) and African American (0.8%) children and adolescents were significantly lower (both P < .001) than in Caucasians (3.5%). Odds of receiving a sleep diagnosis varied among CMCs. CONCLUSIONS: Our analysis of Medicaid claims data of a large urban cohort offers detailed information about the rates of sleep diagnoses and suggests underdiagnosis of SDs in this vulnerable, high-risk, primarily ethnic minority population. Underrecognition of sleep disorders has short- and long-term health and economic consequences. Study results may help clinicians implement appropriate SD screening and management for children and adolescents with CMCs. CITATION: Adavadkar PA, Pappalardo AA, Glassgow AE, et al. Rates of diagnoses of sleep disorders in children with chronic medical conditions. J Clin Sleep Med. 2022;18(8):2001-2007.

Extrathoracic multiple trauma dysregulates neutrophil function and exacerbates pneumonia-induced lung injury.

BACKGROUND: Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues. We hypothesized that PT alone induces priming of neutrophils, resulting in hyperactivation upon secondary exposure to bacteria and causing acute lung injury and increased susceptibility to secondary exposure to Pseudomonas aeruginosa pneumonia. METHODS: C57BL/6 mice were subjected to PT consisting of a lower extremity pseudofracture, liver crush injury, and 15% blood-volume hemorrhage. Pneumonia was induced by intratracheal injection of 5 × 106 CFU live P. aeruginosa or 1 × 107 of heat-killed P. aeruginosa (HKPA). For reactive oxygen species (ROS), studies polymorphonuclear neutrophils (PMNs) were isolated by immunomagnetic bead negative selection and stimulated ex-vivo with HKPA. Reactive oxygen species production was measured by immunofluorescence. For histology, lung sections were stained by hematoxylin-eosin and analyzed by a blinded grader. RESULTS: Polytrauma induced persistent changes in immune function at baseline and to secondary infection. Pneumonia after injury resulted in increased mortality (60% vs. 5% p < 0.01). Blood neutrophils from PT mice had higher resting (unstimulated) ROS production than in naive animals (p < 0.02) demonstrating priming of the neutrophils following PT. After intratracheal HKPA injection, bronchoalveolar lavage PMNs from injured mice had higher ROS production compared with naive mice (p < 0.01), demonstrating an overexuberant immunopathologic response of neutrophils following PT. CONCLUSION: Polytrauma primes neutrophils and causes immunopathologic PMN ROS production, increased lung injury and susceptibility to secondary bacterial pneumonia. These results suggest that trauma-induced immune dysfunction can cause immunopathologic response to secondary infection and suggests neutrophil-mediated pulmonary damage as a therapeutic target for posttrauma pneumonia.

Acute Acalculous Cholecystitis-Associated Bacteremia Has Worse Outcome.

Background: Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder without gallstones in the setting of critical illness. It represents 2%-15% of acute cholecystitis (AC) cases. Bacteremia is associated with increased morbidity and mortality rates in patients in the intensive care unit (ICU). The incidence of bacteremia in acute calculous cholecystitis (ACC) has been described; however, the incidence of bacteremia in AAC has not been reported. We hypothesized that patients with AAC have higher bacteremia rates, leading to worse outcomes than in those with ACC. Methods: A prospectively collected acute care surgery (ACS) institutional database of patients treated from 2008 through 2018 was queried for patients having ACC using International Classification of Diseases (ICD) 9 and 10 codes. Demographics, microbiology findings, and outcomes were extracted. Only patients with positive blood cultures were included in the study. We defined two cohorts: AAC with bacteremia and ACC with bacteremia. The Student t-test was used for continuous variables and the χ2 and Fisher exact tests for categorical variables. Multivariable regression was applied, and statistical significance was set at p < 0.05. Results: Of 323 patients with AC, 57 (17.6%) had AAC and 266 (82.4%) had ACC. Of the 19 patients who had a blood culture, 11 (57.8%) were positive. Patients with positive blood cultures had a mean age of 56.7 ± 15.3 years and a mean Body Mass Index (BMI) of 26.7 ± 4.9. The incidence of bacteremia was significantly higher in AAC (n = 6; 10.5% versus n = 5; 1.9 %; p = 0.005), although the time between admission and diagnosis of bacteremia was similar in the two groups (1.2 ± 1.1 versus 0.2 ± 0.5 days; p = 0.128). The patients with AAC and bacteremia were younger (53.8 ± 19.2 versus 60.2 ± 8 years; p = 0.021) and had a longer ICU length of stay (LOS) (12.6 ± 7.2 versus 1.3 ± 2.1 days; p = 0.030). However, there was no difference in the mortality rate in the groups (n = 2; 33.3% versus 1; 20.0%; p = 1.000). After adjusting for age, gender, BMI, and Charlson Comorbidity Index, bacteremia in AAC patients was found to be an independent variable for longer ICU LOS (odds ratio 8.8; 95% confidence interval 1.7-15.9; p = 0.024). Conclusions: The incidence of bacteremia in patients with AAC is five-fold higher and the ICU stay eight days longer than in patients with ACC.

Backward locomotor treadmill training combined with transcutaneous spinal direct current stimulation in stroke: a randomized pilot feasibility and safety study.

Walking impairment impacts nearly 66% of stroke survivors and is a rising cause of morbidity worldwide. Despite conventional post-stroke rehabilitative care, the majority of stroke survivors experience continued limitations in their walking speed, temporospatial dynamics and walking capacity. Hence, novel and comprehensive approaches are needed to improve the trajectory of walking recovery in stroke survivors. Herein, we test the safety, feasibility and preliminary efficacy of two approaches for post-stroke walking recovery: backward locomotor treadmill training and transcutaneous spinal direct current stimulation. In this double-blinded study, 30 chronic stroke survivors (>6 months post-stroke) with mild-severe residual walking impairment underwent six 30-min sessions (three sessions/week) of backward locomotor treadmill training, with concurrent anodal (N = 19) or sham transcutaneous spinal direct current stimulation (N = 11) over the thoracolumbar spine, in a 2:1 stratified randomized fashion. The primary outcomes were: per cent participant completion, safety and tolerability of these two approaches. In addition, we collected data on training-related changes in overground walking speed, cadence, stride length (baseline, daily, 24-h post-intervention, 2 weeks post-intervention) and walking capacity (baseline, 24-h post-intervention, 2 weeks post-intervention), as secondary exploratory aims testing the preliminary efficacy of these interventions. Eighty-seven per cent (N = 26) of randomized participants completed the study protocol. The majority of the study attrition involved participants with severe baseline walking impairment. There were no serious adverse events in either the backward locomotor treadmill training or transcutaneous spinal direct current stimulation approaches. Also, both groups experienced a clinically meaningful improvement in walking speed immediately post-intervention that persisted at the 2-week follow-up. However, in contrast to our working hypothesis, anodal-transcutaneous spinal direct current stimulation did not enhance the degree of improvement in walking speed and capacity, relative to backward locomotor treadmill training + sham, in our sample. Backward locomotor treadmill training and transcutaneous spinal direct current stimulation are safe and feasible approaches for walking recovery in chronic stroke survivors. Definitive efficacy studies are needed to validate our findings on backward locomotor treadmill training-related changes in walking performance. The results raise interesting questions about mechanisms of locomotor learning in stroke, and well-powered transcutaneous spinal direct current stimulation dosing studies are needed to understand better its potential role as a neuromodulatory adjunct for walking rehabilitation.

Temporary Abdominal Closure Is Associated with Increased Risk for Fungal Intra-Abdominal Infections in Trauma Patients.

Background: Fungal infections are associated with increased morbidity and death. Few studies have examined risk factors associated with post-operative fungal intra-abdominal infections (FIAIs) in trauma patients after exploratory laparotomy. In this study, we evaluated potential risk factors for acquiring post-operative FIAIs and their impact on clinical outcomes. Methods: This was a retrospective analysis of trauma patients admitted from 2005 to 2018 who underwent exploratory laparotomy and subsequently had development of intra-abdominal infection (IAI). Demographics, comorbidities, culture data, antimicrobial usage, Injury Severity Scores (ISS), and clinical outcomes were abstracted. All post-operative IAIs were evaluated and stratified as either bacterial, fungal, combined, and with or without colonization. All groups were compared. Risk factors for the development of post-operative IAI and clinical outcomes were analyzed by Student t test and chi-square test. Multi-variable logistic regression was used to determine independent predictors of post-operative FIAIs. Results: There were 1675 patients identified as having undergone exploratory laparotomy in the setting of traumatic injury, 161 of whom were suspected of having IAI. A total of 105 (6.2%) patients had a diagnosis of IAI. Of these patients, 40 (38%) received a diagnosis of FIAI. The most common fungal pathogens were unspeciated yeast (48.3%), followed by Candida albicans (42.7%), C. glabrata (4.5%), C. dubliniensis (2.25%), and C. tropicalis (2.25%). There were no significant differences in demographics, comorbidities, and percentage of gastric perforations between FIAI and bacterial IAI (BIAI) groups. Patients with FIAIs, however, had a 75% temporary abdominal closure (TAC) rate compared with 51% in BIAIs (p = 0.01). The FIAI group had higher ISS (27 vs. 22, p = 0.03), longer hospital days (34 vs. 25, p = 0.02), and longer intensive care unit (ICU) days (17 vs. 9, p = 0.006) when compared with BIAI. The FIAI group also had a five-fold greater mortality rate. Logistic regression identified TAC as an independent risk factor for the development of post-operative FIAIs (odds ratio [OR] 6.16, confidence interval [CI] 1.14-28.0, p = 0.02). Conclusions: An FIAI after exploratory laparotomy was associated with greater morbidity and death. A TAC was associated independently with increased risk of FIAI after exploratory laparotomy in the setting of traumatic injury. Clinicians should suspect fungal infections in trauma patients in whom post-operative IAI develops after undergoing exploratory laparotomy using TAC techniques.

Revisiting the applicability of adult early post-operative nausea and vomiting risk factors for the paediatric patient: A prospective study using cotinine levels in children undergoing adenotonsillectomies.

BACKGROUND AND AIMS: Post-operative vomiting (POV) in children remains a significant clinical problem. This prospective study aims to investigate the applicability of well-established adult early post-operative nausea and vomiting (PONV) risk factors on paediatric POV after adenotonsillectomies under regulated anaesthetic conditions. METHODS: After Institutional Review Board approval, 213 children aged 3-10-year-old were enrolled. The participants had pre-operative questionnaires completed, followed protocolised anaesthetic plans and had saliva analysed for cotinine. The primary outcomes were POV as correlated with age, gender, family or personal history of PONV, motion sickness history, opioid use, surgical time, anaesthetic time and environmental tobacco smoke (ETS) exposure, as assessed by cotinine levels and questionnaire reports. Data on analgesics, antiemetics and POV incidence before post-anaesthesia care unit discharge were collected. Statistical analysis was done through multiple logistic regression. RESULTS: A total of 200 patients finalised the study. Early POV occurred in 32%. Family history of PONV (odds ratio [OR] = 5.3, P < 0.01) and motion sickness history (OR = 4.4, P = 0.02) were highly significant risk factors. Age reached borderline statistical significance (OR = 1.4, P = 0.05). None of the other factors reached statistical significance. CONCLUSION: Early POV occurs frequently in paediatric patients undergoing adenotonsillectomies. In this paediatric-aged group, the incidence of POV was affected by the family history of PONV, and history of motion sickness. Age, female gender, opioid use, surgical and anaesthetic times did not affect the incidence of POV. ETS exposure, as assessed by cotinine levels and questionnaire reports, had no protective effect on early paediatric POV.

Syringe Pump Performance Maintained with IV Filter Use During Low Flow Rate Delivery for Pediatric Patients.

BACKGROUND: Complex surgical and critically ill pediatric patients rely on syringe infusion pumps for precise delivery of IV medications. Low flow rates and in-line IV filter use may affect drug delivery. To determine the effects of an in-line filter to remove air and/or contaminants on syringe pump performance at low flow rates, we compared the measured rates with the programmed flow rates with and without in-line IV filters. METHODS: Standardized IV infusion assemblies with and without IV filters (filter and control groups) attached to a 10-mL syringe were primed and then loaded onto a syringe pump and connected to a 16-gauge, 16-cm single-lumen catheter. The catheter was suspended in a normal saline fluid column to simulate the back pressure from central venous circulation. The delivered infusate was measured by gravimetric methods at predetermined time intervals, and flow rate was calculated. Experimental trials for initial programmed rates of 1.0, 0.8, 0.6, and 0.4 mL/h were performed in control and filter groups. For each trial, the flow rate was changed to double the initial flow rate and was then returned to the initial flow rate to analyze pump performance for titration of rates often required during medication administration. These conditions (initial rate, doubling of initial rate, and return to initial rate) were analyzed separately for steady-state flow rate and time to steady state, whereas their average was used for percent deviation analysis. Differences between control and filter groups were assessed using Student t tests with adjustment for multiplicity (using n = 3 replications per group). RESULTS: Mean time from 0 to initial flow (startup delay) was <1 minute in both groups with no statistical difference between groups (P = 1.0). The average time to reach steady-state flow after infusion startup or rate changes was not statistically different between the groups (range, 0.8-5.5 minutes), for any flow rate or part of the trial (initial rate, doubling of initial rate, and return to initial rate), although the study was underpowered to detect small time differences. Overall, the mean steady-state flow rate for each trial was below the programmed flow rate with negative mean percent deviations for each trial. In the 1.0-mL/h initial rate trial, the steady-state flow rate attained was lower in the filter than the control group for the initial rate (P = 0.04) and doubling of initial rate (P = 0.04) with a trend during the return to initial rate (P = 0.06), although this same effect was not observed when doubling the initial rate trials of 0.8 or 0.6 mL/h or any other rate trials compared with the control group. CONCLUSIONS: With low flow rates used in complex surgical and pediatric critically ill patients, the addition of IV filters did not confer statistically significant changes in startup delay, flow variability, or time to reach steady-state flow of medications administered by syringe infusion pumps. The overall flow rate was lower than programmed flow rate with or without a filter.

PyEEG: an open source Python module for EEG/MEG feature extraction.

Computer-aided diagnosis of neural diseases from EEG signals (or other physiological signals that can be treated as time series, e.g., MEG) is an emerging field that has gained much attention in past years. Extracting features is a key component in the analysis of EEG signals. In our previous works, we have implemented many EEG feature extraction functions in the Python programming language. As Python is gaining more ground in scientific computing, an open source Python module for extracting EEG features has the potential to save much time for computational neuroscientists. In this paper, we introduce PyEEG, an open source Python module for EEG feature extraction.