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ObjectiveThis study aimed to detect novel mesenchymal stem cell peptides/biomarkers of bronchopulmonary dysplasia (BPD) in the tracheal aspirate fluid (TAF) of preterm infants.Study designParticipants included infants less than 32 weeks' gestational age or birth weight under 1500 grams who required endotracheal intubation and mechanical ventilation within first 24 hours of life. TAF sample collection was performed at the time of the first clinically indicated routine suctioning. Standardization curves for human levels of osteopontin (Opn), macrophage colony stimulating factor 1 (Csf1), transforming growth factor beta 1 (TGF-β1), and secretory immunoglobulin A (sIgA) were generated for 15 enrolled participants.ResultsWe demonstrated that stem cell biomarkers are secreted into the TAF of preterm infants and their concentrations can be easily measured during the first week of life.ConclusionsFurther studies are warranted to determine a causal relationship between these biomarkers and BPD development and severity.

ObjectiveTo determine whether prenatal treatment with a single course of glucocorticoids (GCs) affects size at birth among full-term infants independent of fetal size before GC administration or exposure to preterm labor (PTL).Study designIn all, 105 full-term infants were recruited into three study groups (30 GC treated; 60 controls matched for gestational age (GA) at birth and sex; and 15 PTL controls without GC exposure). Size of the infants was estimated before treatment using two-dimensional (2D) ultrasound and by direct measurement at birth.ResultsLength, weight and head circumference at birth were smaller among GC-treated infants compared with matched controls (P's0.2). Exposure to PTL did not account for this effect.ConclusionsPrenatal treatment with a single course of GCs was associated with a reduction in size at birth among infants born at term gestation. This effect cannot be explained by differences in fetal size before treatment or exposure to PTL.

OBJECTIVE: This study aimed to detect novel mesenchymal stem cell peptides/biomarkers of bronchopulmonary dysplasia (BPD) in the tracheal aspirate fluid (TAF) of preterm infants. STUDY DESIGN: Participants included infants less than 32 weeks' gestational age or birth weight under 1500 grams who required endotracheal intubation and mechanical ventilation within first 24 hours of life. TAF sample collection was performed at the time of the first clinically indicated routine suctioning. Standardization curves for human levels of osteopontin (Opn), macrophage colony stimulating factor 1 (Csf1), transforming growth factor beta 1 (TGF-β1), and secretory immunoglobulin A (sIgA) were generated for 15 enrolled participants. RESULTS: We demonstrated that stem cell biomarkers are secreted into the TAF of preterm infants and their concentrations can be easily measured during the first week of life. CONCLUSIONS: Further studies are warranted to determine a causal relationship between these biomarkers and BPD development and severity. [ABSTRACT FROM AUTHOR]

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood product transfusion characterized by sudden onset hypoxemic respiratory failure with bilateral lung infiltrates and non-cardiogenic pulmonary edema developing within 6 hours of transfusion. It is believed to be under-recognized, particularly among preterm neonates in whom co-existing developmental lung disease adds diagnostic complexity. Here we report the case of a preterm neonate who developed TRALI during a blood transfusion following PDA ligation. [ABSTRACT FROM AUTHOR]

Pneumatosis intestinalis and free intraperitoneal air on abdominal radiographs are considered pathognomonic signs of necrotizing enterocolitis (NEC). We report a unique case of late-onset fulminant sepsis due to Clostridium perfringens presenting with shock, extensive pneumatosis intestinalis and free intraperitoneal air in an extremely low birth weight infant without histopathological evidence of bowel necrosis or NEC. [ABSTRACT FROM AUTHOR]

Objective: Spontaneous intestinal perforations (SIP) in extremely low birth weight infants are distinctly different from necrotizing enterocolitis. The etiology of SIP is not well understood. Our objective was to identify perinatal therapeutic interventions that may increase the risk of spontaneous intestinal perforations. Methods: Medical records of extremely low birth weight infants (BW<1000g) admitted to a neonatal intensive care unit during 42-month period were studied. Infants with radiologic or histologic diagnosis of necrotizing enterocolitis were excluded. Information collected included maternal and infant demographics, perinatal risk factors, clinical findings and interventions, and exposure to medications before and after delivery. Chi square and paired t-tests were used to compare SIP patients to those with no perforation (NP). Mean values are given with standard error of the mean. Results: There were 13 SIP and 165 NP. There were more male infants (84.6% vs 49.1%, p<0.025) and more out born in-fants (61.5% vs 39.9%, p<0.05) in the SIP group. The use of maternal tertbutaline was higher in the SIP group (30.8% vs 9.1%, p<0.015). Early treatment with indomethacin (0-3days) was significantly higher in the SIP group (69.2% vs 27.9%, p=0.002). Hypotension requiring dopamine was significantly higher in the SIP group (69.2% vs 34.6%, p=0.017). Com-bined exposure to antenatal steroids and postnatal indomethacin was significantly higher in the SIP group (69.2% vs 36.4%, p=0.019), as was the combined early treatment with hydrocortisone and indomethacin (7.7% vs 0.6%, p=0.02). Conclusions: Early use of indomethacin, and co-exposure to antenatal or postnatal steroids is related to development of spontaneous intestinal perforation in extremely low birth weight infants. Prenatal exposure to maternal terbutaline and postnatal use of dopamine for hypotension increases the risk for SIP in these infants. [ABSTRACT FROM AUTHOR]

Abstract Background Malnutrition is a problem for many older people recovering from a hip and other major fractures. Oral supplementation with high calorie high protein nutrients is a simple intervention that may help older people with fractures to improve their recovery in terms of rehabilitation time, length of hospital stay and mortality. This paper reports a pilot study to test the feasibility of a trial initiated in a hospital setting with an oral supplement to older people with recent fractures. Method A randomized controlled trial with 44 undernourished participants admitted to a hospital following a fracture. The intervention group (n = 23) received a high calorie high protein supplement for forty days in addition to their diet of choice. The control group (n = 21) received high protein milk during their hospital stay in addition to their diet of choice and their usual diet when discharged from hospital. Results All participants were women and their mean age was 85.3 (± 6.1) years. Twenty nine (65%) participants had a hip fracture. At baseline no differences were measured between the two groups regarding their nutritional status, their cognitive ability or their abilities in activities of daily living. There were no significant differences between the intervention and control group with reference to nutritional or functional parameters at 40 day and 4 month follow-ups. Median length of stay in hospital was 18.0 days, with 12 participants being readmitted for a median of 7.0 days. Conclusion It is feasible to perform a randomised trial in a hospital and community setting to test the effect of an oral high energy high protein supplement for older people. Due to the limited number of participants and incomplete adherence with use of the supplements no conclusion can be drawn about the efficacy or effectiveness of this intervention.

Background: The University of California Fetal Consortium published that 55% of infants with gastroschisis develop growth faltering by hospital discharge. To address this problem, we developed a nutrition pathway emphasizing (1) early provision of parenteral macronutrients, (2) use of human milk, and (3) growth faltering treatment. This study's goals were to assess adherence to and efficacy of this pathway in infants with gastroschisis across six California hospitals., Methods: In 2015, the consortium standardized the care for infants with gastroschisis. To decrease growth faltering rates, between 2019 and 2020, nutrition guidelines were proposed, discussed, revised, and initiated. This study's primary outcome was weight or linear growth faltering (z score decline ≥0.8 in weight or length) at hospital discharge. Adherence measures were assessed., Results: One hundred twenty-six infants with gastroschisis were born prepathway; 52 were born postpathway. Median gestational age was similar between cohorts. Adherence to components of the pathway ranged from 58% to 95%. The proportion of infants with weight or linear growth faltering at discharge was lower after pathway initiation (59.4% vs 36.2%, P = 0.0068). Adjusting for gestational age and fetal growth restriction, the pathway was associated with decreased weight or linear growth faltering (odds ratio [OR] 0.35 [0.16-0.75], P = 0.0060) and decreased linear growth faltering (OR 0.24 [0.096-0.56], P = 0.0062) at discharge. Hypertriglyceridemia, cholestasis, and days to full feeds were similar to published cohorts., Conclusion: Fewer infants with gastroschisis experienced weight or length growth faltering at hospital discharge following the implementation of a multicenter nutrition pathway., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

This study describes the deployment process of an AI-driven clinical decision support (CDS) system to support postpartum depression (PPD) prevention, diagnosis and management. Central to this CDS is an L2-regularized logistic regression model trained on electronic health record (EHR) data at an academic medical center, and subsequently refined through a broader dataset from a consortium to ensure its generalizability and fairness. The deployment architecture leveraged Microsoft Azure to facilitate a scalable, secure, and efficient operational framework. We used Fast Healthcare Interoperability Resources (FHIR) for data extraction and ingestion between the two systems. Continuous Integration/Continuous Deployment pipelines automated the deployment and ongoing maintenance, ensuring the system's adaptability to evolving clinical data. Along the technical preparation, we focused on a seamless integration of the CDS within the clinical workflow, presenting risk assessment directly within the clinician schedule and providing options for subsequent actions. The developed CDS is expected to drive a PPD clinical pathway to enable efficient PPD risk management., (©2024 AMIA - All rights reserved.)

Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a combination of MeSH Terms and free-text keywords in September 2021. No other mood disorders or psychiatric diagnoses were included. Original papers in English were included. The PRISMA framework was followed for the screening of papers. Two researchers screened the retrieved articles from the literature search, and a third researcher resolved any conflicts. Of 2,193 papers identified, 49 were selected for full-text review. 14 articles were included in the qualitative synthesis. Six supported psilocybin's mechanism of antidepressant action via changes to serotonin or glutamate receptor activity and three papers found an increase in synaptogenesis. Thirteen papers investigated changes in non-receptor or pathway-specific brain activity. Five papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex. Several neuroreceptors, neurotransmitters, and brain areas are thought to be involved in psilocybin's ability to mitigate depressive symptoms. Psilocybin appears to alter cerebral blood flow to the amygdala and prefrontal cortex, but the evidence on changes in functional connectivity and specific receptor activity remains sparse. The lack of consensus between studies suggests that psilocybin's mechanism of action may involve a variety of pathways, demonstrating the need for more studies on psilocybin's mechanism of action as an antidepressant.

Objective: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age., Study Design: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 μIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database., Results: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 μIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 μIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 μIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity., Conclusions: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy., Competing Interests: Declaration of Competing Interest This study was funded through an intramural funding provided by the Division of Neonatology, Department of Pediatrics, University of CaliforniaIrvine. The authors reported no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.

BACKGROUND: Management strategies for preterm neonates with respiratory distress syndrome include early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen and may include the use of less invasive surfactant administration (LISA) to avoid the need for endotracheal intubation. This randomized trial investigated whether early administration of caffeine and LISA would decrease the need for endotracheal intubation in the first 72 hours of life (HoL) compared with caffeine and CPAP alone. METHODS: Eligible neonates born at 24 weeks 0 days to 29 weeks 6 days of gestational age were randomly assigned to receive intravenous caffeine in the first 2 HoL followed by surfactant administration via the LISA method (intervention) or caffeine followed by CPAP (control). The primary outcome was the frequency of neonates requiring endotracheal intubation or meeting respiratory failure criteria between groups (caffeine and LISA vs. caffeine and CPAP) within the first 72 HoL. Multivariable logistic regression modeling was used to adjust for gestational age strata in normally distributed primary and secondary outcomes. RESULTS: Enrollment occurred between January 2020 and December 2022. Endotracheal intubation or meeting respiratory failure criteria within the first 72 HoL occurred in 21 (23%) of 92 neonates randomly assigned to receive caffeine and LISA compared with 47 (53%) of 88 neonates in the caffeine and CPAP group (odds ratio, 0.258; 95% confidence interval, 0.136 to 0.490; P<0.001), which remained significant after adjusting for gestational age strata (odds ratio, 0.227; 95% confidence interval, 0.112 to 0.460; P<0.001). Adverse events were similar between groups, except bronchopulmonary dysplasia, which occurred in 26% of the LISA group and 39% of the control group (P=0.049). CONCLUSIONS: In preterm neonates supported with CPAP, early caffeine and LISA resulted in a lower frequency of endotracheal intubation within the first 72 HoL. (Funded by Chiesi USA; ClinicalTrials.gov number, NCT04209946.)

Objective: To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak., Design: Prospective observational study., Setting: Neonatal intensive care unit (NICU)., Methods: We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates., Results: A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak., Conclusions: In comparison to fast outbreaks, outbreaks that are "slow and sustained" may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.

Study Objectives: Limited data exist concerning the indications, parameters, utility of daytime polysomnography, and treatment of infants with suspected sleep-related breathing disorders., Methods: We retrospectively reviewed all polysomnography undertaken in a quaternary pediatric hospital for term infants up to 6 months of age between January 2017 and December 2019. Outcomes were evaluated, including a comparison among diagnostic groups., Results: Of 161 infants (58% male), 77 (48%) were ≤ 2 months old, and 103 (61%) were referred for either craniofacial abnormalities or an airway malformation. Daytime (n = 100) vs nighttime (n = 61) studies showed no differences in sleep architecture or treatment rates. Apnea-hypopnea index was > 10 events/h in 137 (85%) and was similar across different diagnostic groups, and 97 (78%) were prescribed noninvasive ventilation, with a mean treatment duration of 13.4 ± 9 months. Of the infants who were commenced on noninvasive ventilation 75% did not require it beyond 24 months., Conclusions: Polysomnographic sleep parameters and the number of treatments prescribed were equivalent whether the polysomnography was performed during daytime or nighttime. Treatment with noninvasive ventilation was required in the short term for most infants with sleep-related breathing disorders, regardless of the indication for referral., Citation: Singh J, Yeoh E, Castro C, Uy C, Waters K. Polysomnography in infants with clinical suspicion of sleep-related breathing disorders. J Clin Sleep Med . 2022;18(12):2803-2812., (© 2022 American Academy of Sleep Medicine.)

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine., Competing Interests: Conflict of interest Nil for any authors., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised 'onconeuronal' antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient help to determine the clinical relevance of the syndrome and hence guide its management. We summarise current knowledge and a practical approach to the investigation, diagnosis, treatment and outcomes of patients with suspected PNS., Competing Interests: Competing interests: SRI is a coapplicant and receives royalties on patent application WO/2010/046716 (UK patent number, PCT/GB2009/051441) entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed commercially for the development of assays for LGI1 and other VGKC complex antibodies. SRI and SB are coapplicants on a patent application entitled 'Diagnostic Strategy to Improve Specificity of CASPR2 Antibody Detection' (PCT/GB2019/051257, publication number WO/2019/211633 and UK1807410.4). SRI has received honoraria from UCB, MedImmun, ADC therapeutics and Medlink Neurology, and research support from CSL Behring, UCB and ONO Pharma. CU and JH declare no competing interests with respect to this publication., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis., Study Design: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study's primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time., Results: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35-37). Length of stay was 32 days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14 days, 30 days, and discharge were less than birth (P < .01 for all). Weight and length z scores declined from birth to 30 days (-0.10 and -0.11 z score units/week, respectively, P < .001). Length growth failure at discharge was associated with weight and length z score changes over time (P < .05 for both). Lower gestational age was associated with weight growth failure (OR 0.70 for each gestational age week, 95% CI 0.55-0.89, P = .004)., Conclusions: Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants., (Copyright © 2021 Elsevier Inc. All rights reserved.)