We Are Not Speaking the Same Language: Current Procedural Terminology Coding and Provision of Care in Lymphatic Reconstruction.

INTRODUCTION: Current Procedural Terminology (CPT) codes provide a uniform language for medical billing, but specific codes have not been assigned for lymphatic reconstruction techniques. The authors hypothesized that inadequate codes would contribute to heterogeneous coding practices and reimbursement challenges, ultimately limiting surgeons' ability to treat patients. METHODS: A 22-item virtual questionnaire was offered to 959 members of the American Society of Reconstructive Microsurgeons to assess the volume of lymphatic reconstruction procedures performed, CPT codes used for each procedure, and challenges related to coding and providing care. RESULTS: The survey was completed by 66 board-certified/board-eligible plastic surgeons (6.9%), who unanimously agreed that lymphatic surgery is integral to cancer care, with 86.4% indicating that immediate lymphatic reconstruction should be offered after lymphadenectomy. Most performed lymphovenous bypass, immediate lymphatic reconstruction, liposuction, and vascularized lymph node transfer.Respondents reported that available CPT codes failed to reflect procedural scope. A wide variety of CPT codes was used to report each type of procedure. Insurance coverage problems led to 69.7% of respondents forgoing operations and 32% reducing treatment offerings. Insurance coverage and CPT codes were identified as significant barriers to care by 98.5% and 95.5% of respondents, respectively. CONCLUSIONS: Respondents unanimously agreed on the importance of lymphatic reconstruction in cancer care, and most identified inadequate CPT codes as causing billing issues, which hindered their ability to offer surgical treatment. Appropriate and specific CPT codes are necessary to ensure accuracy and consistency of reporting and ultimately to improve patient access to care.

Titratable residues that drive RND efflux: Insights from molecular simulations.

The resistance-nodulation-division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump. Given the difficulties in studying proton movement using even state-of-the-art structural biology methods, the contributions from computational studies have been invaluable from a mechanistic perspective.

Utility of a Neuromuscular Activation Exercise Protocol on Surgeon Posture.

BACKGROUND: Surgeons are at risk for musculoskeletal disorders from ergonomic strain in the operating room. These deficits may stem from neuromuscular control deficits. Neuromuscular activation exercises (NMEs) may strengthen the brain-muscle connection. This study aimed to assess the utility of a surgeon-oriented NME protocol on posture. METHODS: Surgeons, operating room staff, and medical students completed a professionally established NME routine. An electronic application, PostureScreen®, assessed participants' posture. A long-term cohort was assessed before and after a 2 to 6-week routine. A short-term cohort was assessed immediately before and after completion. All participants additionally completed a postintervention survey. RESULTS: After intervention, the short-term cohort (n = 47) had significantly reduced frontal and sagittal postural deviation (P < 0.05). A significant decrease in effective head weight was additionally demonstrated with decreased neck flexion and increased cerebral-cervical symmetry (P < 0.05).The long-term cohort (n = 6) showed a significant postintervention decrease in lateral and anterior shoulder translation (P < 0.05). Total anterior translational deviations demonstrated trend-level decrease (P = 0.078). This demonstrates that after intervention, participants' shoulders were more centered with the spine as opposed to shifted right or left. Survey results showed participants favored exercises that immediately brought relief of tension. CONCLUSIONS: A decrease in postural deviations associated with NME in both cohorts demonstrates NME as a potential mechanism to protect surgeon musculoskeletal health and improve well-being. Survey results demonstrate areas of refinement for NME protocol design.

Ecological and anthropogenic drivers of waterfowl productivity are synchronous across species, space, and time.

Knowledge of interspecific and spatiotemporal variation in demography-environment relationships is key for understanding the population dynamics of sympatric species and developing multispecies conservation strategies. We used hierarchical random-effects models to examine interspecific and spatial variation in annual productivity in six migratory ducks (i.e., American wigeon [Mareca americana], blue-winged teal [Spatula discors], gadwall [Mareca strepera], green-winged teal [Anas crecca], mallard [Anas platyrhynchos] and northern pintail [Anas acuta]) across six distinct ecostrata in the Prairie Pothole Region of North America. We tested whether breeding habitat conditions (seasonal pond counts, agricultural intensification, and grassland acreage) or cross-seasonal effects (indexed by flooded rice acreage in primary wintering areas) better explained variation in the proportion of juveniles captured during late summer banding. The proportion of juveniles (i.e., productivity) was highly variable within species and ecostrata throughout 1961-2019 and generally declined through time in blue-winged teal, gadwall, mallard, pintail, and wigeon, but there was no support for a trend in green-winged teal. Productivity in Canadian ecostrata declined with increasing agricultural intensification and increased with increasing pond counts. We also found a strong cross-seasonal effect, whereby more flooded rice hectares during winter resulted in higher subsequent productivity. Our results suggest highly consistent environmental and anthropogenic effects on waterfowl productivity across species and space. Our study advances our understanding of current year and cross-seasonal effects on duck productivity across a suite of species and at finer spatial scales, which could help managers better target working-lands conservation programs on both breeding and wintering areas. We encourage other researchers to evaluate environmental drivers of population dynamics among species in a single modeling framework for a deeper understanding of whether conservation plans should be generalized or customized given limited financial resources.

An Interdisciplinary, Comprehensive Recovery Pathway Improves Microsurgical Breast Reconstruction Delivery.

INTRODUCTION: Free-flap (autologous) breast reconstruction demonstrates superiority over alloplastic approaches but is offered infrequently. Enhanced recovery protocols can address postoperative challenges, but most literature is limited to inpatient interventions and outcomes. This study describes an adoptable, longitudinally comprehensive and multidisciplinary recovery pathway for autologous reconstruction which adds to the current guidelines. The authors aimed to allow perioperative outcomes comparable to alloplastic reconstructions. METHODS: All autologous Comprehensive Recovery Pathway (CRP) subjects from a single surgeon were retrospectively included. A comparator group of equal size was randomly selected from institutional subpectoral and dual-plane tissue expander patients having Enhanced Recovery After Surgery guideline-directed care. All subjects in both cohorts received preoperative paravertebral regional blocks. Operative detail, inpatient recovery, longitudinal morphine equivalents (MEs) required, and complications were compared. RESULTS: Each cohort included 71 cases (99 breasts). Despite longer operations, intraoperative MEs were fewer in autologous cases ( P = 0.02). Morphine equivalents during inpatient stay were similar between cohorts, with both being discharged on median day 2. Multivariate regression demonstrated a 0.8-day increased stay for autologous subjects with additional contribution from bilateral cases, body mass index, and age ( P < 0.05). Autologous subjects were regularly discharged postoperative day 1 (17%) and postoperative day 2 (39%), with trend toward earlier discharge ( P < 0.01). Outpatient MEs were significantly fewer in autologous subjects, corresponding to a 30- to 150-mg oxycodone difference ( P < 0.01). Major complication occurred in 12.7% of autologous and 22.5% of alloplastic subjects ( P = 0.11). Flap loss occurred in 1 autologous subject versus 11 alloplastic failures ( P < 0.01). CONCLUSIONS: This study details partnership between the plastic surgery service, regional and acute pain anesthesia services, and dedicated nursing with longitudinal optimizations allowing perioperative outcomes improved over current literature. Patients in the CRP used fewer opioids from operation through follow-up with comparable length of stay and significantly fewer reconstructive failures than alloplastic subjects. The pathway may be quickly adopted into academic practice patterns and mitigates traditional barriers, allowing extension of autologous reconstruction offerings.

Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.

Unfolding an Elusive Area-Selective Deposition Process: Atomic Layer Deposition of TiO2 and TiON on SiN vs SiO2.

Area-selective atomic layer deposition (AS-ALD) processes for TiO2 and TiON on SiN as the growth area vs SiO2 as the nongrowth area are demonstrated on patterns created by state-of-the-art 300 mm semiconductor wafer fabrication. The processes consist of an in situ CF4/N2 plasma etching step that has the dual role of removing the SiN native oxide and passivating the SiO2 surface with fluorinated species, thus rendering the latter surface less reactive toward titanium tetrachloride (TiCl4) precursor. Additionally, (dimethylamino)trimethylsilane was employed as a small molecule inhibitor (SMI) to further enhance the selectivity. Virtually perfect selectivity was obtained when combining the deposition process with intermittent CF4/N2 plasma-based back-etching steps, as demonstrated by scanning and transmission electron microscopy inspections. Application-compatible thicknesses of ∼8 and ∼5 nm were obtained for thermal ALD of TiO2 and plasma ALD of TiON.

The AI-driven Drug Design (AIDD) platform: an interactive multi-parameter optimization system integrating molecular evolution with physiologically based pharmacokinetic simulations.

Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have demonstrated the contribution of this field to medicine. Properly designed and implemented platforms can drastically reduce drug development timelines and costs. While such efforts were initially focused primarily on target affinity/activity, it is now appreciated that other parameters are equally important in the successful development of a drug and its progression to the clinic, including pharmacokinetic properties as well as absorption, distribution, metabolic, excretion and toxicological (ADMET) properties. In the last decade, several programs have been developed that incorporate these properties into the drug design and optimization process and to varying degrees, allowing for multi-parameter optimization. Here, we introduce the Artificial Intelligence-driven Drug Design (AIDD) platform, which automates the drug design process by integrating high-throughput physiologically-based pharmacokinetic simulations (powered by GastroPlus) and ADMET predictions (powered by ADMET Predictor) with an advanced evolutionary algorithm that is quite different than current generative models. AIDD uses these and other estimates in iteratively performing multi-objective optimizations to produce novel molecules that are active and lead-like. Here we describe the AIDD workflow and details of the methodologies involved therein. We use a dataset of triazolopyrimidine inhibitors of the dihydroorotate dehydrogenase from Plasmodium falciparum to illustrate how AIDD generates novel sets of molecules.

Tracking flight activity of potato leafhopper (Hemiptera: Cicadellidae) with the Midwest Suction Trap Network.

Potato leafhopper (PLH), Empoasca fabae Harris (Hemiptera: Cicadellidae), is an economic pest of a variety of crops that migrates between overwintering sites in the southern United States and northern breeding grounds. Since 2005, the Midwest Suction Trap Network (STN) has monitored the magnitude and timing of aerially dispersing aphids' activity, but the potential of the network to monitor other taxa is only beginning to be explored. Here, we use the Midwest STN to examine how the magnitude and timing of PLH activity vary with weather, cropland cover, and time of year. We found that weekly PLH activity increased early in the season (May-June) with increasing degree day accumulation and decreased mid-season (July-August) with increasing occurrence of rain. The first detections occurred earlier in southern latitudes, while the last detections occurred sooner, when there was more surrounding potato land cover, and later over time between 2018 and 2021 and in southern latitudes. PLH activity was thus longer in duration in southern latitudes and has continued to extend later into the year overall. Resolving uncertainty about how well the Midwest STN captures migratory activity and how closely suction trap detections reflect local population densities in crop fields remain important research priorities before the potential of the Midwest STN for PLH monitoring can be realized. Still, observed patterns suggest that PLH could increase in economic importance as insects disperse over larger portions of the growing season in the warming, agriculturally productive US Midwest and that the STN can become a useful tool to monitor these changes.

Etiology of Drug-Induced Edema: A Review of Dihydropyridine, Thiazolidinedione, and Other Medications Causing Edema.

Edema is an accumulation of fluid in the body's tissues that affects millions of Americans yearly. It can affect multiple body parts, for example, the brain or eyes, but often occurs in the periphery, including the feet and legs. Medications, such as dihydropyridine and thiazolidinediones (TZDs), can be the etiology of edema. Edema can develop in association with problems in the vasculature or lymphatic flow. In recent years, a better understanding of these drug-induced mechanisms has been appreciated. Specifically, dihydropyridines can increase hydrostatic pressure and cause selective pre-capillary vessel vasodilation. TZDs can cause edema through increased vascular permeability and increased hydrostatic pressure. Specifically, peroxisome proliferator-activated receptor gamma (PPARγ) stimulation increases vascular endothelial permeability, vascular endothelial growth factor (VEGF) secretion, renal sodium, and fluid retention. Other drugs that can cause edema include neuropathic pain agents, dopamine agonists, antipsychotics, nitrates, nonsteroidal anti-inflammatory (NSAIDS), steroids, angiotensin-converting enzyme (ACE) inhibitors, and insulin. There are various clinical presentations of edema. Since multiple mechanisms can induce edema, it is important to understand the basic mechanisms and pathophysiology of drug-induced edema. Edema can even become fatal. For example, angioedema can occur from ACE inhibitor therapy. In this regard, it is considered a medical emergency when there is laryngeal involvement. This review aims to thoroughly appreciate the multiple causes of drug-induced edema and the ways it can be treated or prevented.

A clinical practice review of percutaneous ethanol injection for thyroid nodules: state of the art for benign, cystic lesions.

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

OBJECTIVES: Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. DESIGN: Retrospective, electronic medical record linkage, cohort study. SETTING: Quaternary PICU. PATIENTS: Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). MEASUREMENTS AND MAIN RESULTS: ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. CONCLUSIONS: A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

Precision-cut lung slices as an ex vivo model to study Pneumocystis murina survival and antimicrobial susceptibility.

IMPORTANCE: Our study reveals the potential of precision-cut lung slices as an ex vivo platform to study the growth/survival of Pneumocystis spp. that can facilitate the development of new anti-fungal drugs.

An assessment of immediate newborn care readiness and availability in Nepal.

BACKGROUND: Global neonatal mortality necessitates access to immediate newborn care interventions. In Nepal, disparities persist in the readiness and availability of newborn care services within health facilities. OBJECTIVE: This study aimed to assess this status and compare facilities that had implemented an intensive newborn resuscitation capacity building and retention programme in the past five years with those that had not. METHODS: Our observational cross-sectional study involved 154 health facilities across Nepal. Through on-site inspections and maternal log reviews, we evaluated the immediate newborn care readiness and availability. RESULTS: The mean immediate newborn care intervention availability score of 52.8% (SE = 21.5) and the readiness score averaged 79.6% (SE = 12.3). Encouragingly, 96% of facilities ensured newborns were dried and wrapped for warmth, and 69.9% provided newborn resuscitation. Practices such as delayed cord clamping (42.0%), skin-to-skin contact (28.6%), and early breastfeeding (63.5%) showed room for improvement. Only 16.1% of health facilities administered Vitamin K1 prophylaxis.Domain-specific scores demonstrated a high level of facility readiness in infrastructure (97.5%), medicine, equipment, and supplies (90.6%), and staff training (90.9%), but a lower score for neonatal resuscitation aids (28.8%). Disparities in readiness and availability were evident, with rural areas and the Madhesh province reporting lower scores. Variations among health facility types revealed provincial and private hospitals outperforming local-level facilities. A positive association was observed between the LDSC/SSN mentoring programme and both the readiness and availability of immediate newborn care services. CONCLUSION: This study highlights the gap between healthcare facility readiness and the actual availability of immediate newborn care interventions in Nepal. Addressing disparities and barriers, particularly in rural areas and local-level facilities, is crucial for improving neonatal survival. The positive link between the LDSC/SSN programme and service availability and facility readiness emphasises the significance of targeted training and mentorship programmes in enhancing newborn care across Nepal.

Phospholipid transport to the bacterial outer membrane through an envelope-spanning bridge.

The outer membrane of Gram-negative bacteria provides a formidable barrier, essential for both pathogenesis and antimicrobial resistance. Biogenesis of the outer membrane requires the transport of phospholipids across the cell envelope. Recently, YhdP was implicated as a major protagonist in the transport of phospholipids from the inner membrane to the outer membrane however the molecular mechanism of YhdP mediated transport remains elusive. Here, utilising AlphaFold, we observe YhdP to form an elongated assembly of 60 ß strands that curve to form a continuous hydrophobic groove. This architecture is consistent with our negative stain electron microscopy data which reveals YhdP to be approximately 250 Å in length and thus sufficient to span the bacterial cell envelope. Furthermore, molecular dynamics simulations and in vivo bacterial growth assays indicate essential helical regions at the N- and C-termini of YhdP, that may embed into the inner and outer membranes respectively, reinforcing its envelope spanning nature. Our in vivo crosslinking data reveal phosphate-containing substrates captured along the length of the YhdP groove, providing direct evidence that YhdP transports phospholipids. This finding is congruent with our molecular dynamics simulations which demonstrate the propensity for inner membrane lipids to spontaneously enter the groove of YhdP. Collectively, our results support a model in which YhdP bridges the cell envelope, providing a hydrophobic environment for the transport of phospholipids to the outer membrane.

Significance of intramedullary T2* signal voids in the magnetic resonance imaging of paraplegic deep pain-negative dogs following intervertebral disc extrusion at short-term follow-up.

Introduction: Dogs presenting as paraplegic without nociception due to a thoracolumbar intervertebral disc extrusion provide a difficult decision to both the clinician and the owner. The prognosis when performing surgical decompression remains guarded. Aside from significant extradural compression, these dogs often have a significant secondary spinal cord injury, which has shown to be an important factor in determining both the likelihood of developing progressive myelomalacia and the return to ambulation. Materials and methods: This is a retrospective, observational, single centre study including 82 dogs presenting as paraplegic with absent nociception diagnosed with an intervertebral disc extrusion. Patients underwent MRI of the thoracolumbar spine, including a gradient echo sequence which was evaluated for the presence of intramedullary signal void artefacts. Decompressive surgery was performed, and patients were evaluated for the presence of nociception at short term follow up (at least four weeks post-surgery). Results: Overall, 59.8% of patients regained nociception within the study period. This number was significantly reduced to 33.3% when multiple gradient echo signal voids were present (compared to 67.3% of dogs without signal voids). There was no significant difference in the rate of developing progressive myelomalacia between groups. Conclusions: This paper adds to the existing literature and suggests that the gradient echo sequence may be of use when assessing acute spinal cord injury in the context of intervertebral disc extrusion and how it relates to prognosis.

Metabolism of serine/glycine lipids by human gingival cells in culture.

Porphyromonas gingivalis produces five classes of serine/glycine lipids that are recovered in lipid extracts from periodontitis-afflicted teeth and diseased gingival tissues, particularly at sites of periodontitis. Because these lipids are recovered in diseased gingival tissues, the purpose of the present study was to evaluate the capacity of cultured human gingival fibroblasts (HGF), keratinocytes, and macrophages to hydrolyze these lipids. We hypothesize that one or more of these cell types will hydrolyze the serine/glycine lipids. The primary aim was to treat these cell types for increasing time in culture with individual highly enriched serine/glycine lipid preparations. At specified times, cells and culture media samples were harvested and extracted for hydrolysis products. The serine/glycine lipids and hydrolysis products were quantified using liquid chromatography-mass spectrometry (LC-MS) and free fatty acids were quantified using gas chromatograph-mass spectrometer. LC-MS analysis used two different mass spectrometric methods. This study revealed that treatment of HGF or macrophage (THP1) cells with lipid (L) 654 resulted in breakdown to L342 and subsequent release into culture medium. However, L654 was converted only to L567 in gingival keratinocytes. By contrast, L1256 was converted to L654 by fibroblasts and macrophages but no further hydrolysis or release into medium was observed. Gingival keratinocytes showed no hydrolysis of L1256 to smaller lipid products but because L1256 was not recovered in these cells, it is not clear what hydrolysis products are produced from L1256. Although primary cultures of gingival fibroblasts and macrophages are capable of hydrolyzing specific serine/glycine lipids, prior analysis of lipid extracts from diseased gingival tissues revealed significantly elevated levels of L1256 in diseased tissues. These results suggest that the hydrolysis of bacterial lipids in gingival tissues may reduce the levels of specific lipids, but the hydrolysis of L1256 is not sufficiently rapid to prevent significant accumulation at periodontal disease sites.

Characterization of Circulating Cold Shock Proteins FGF21 and RBM3 in a Multi-Center Study of Pediatric Cardiac Arrest.

Fibroblast Growth Factor 21 (FGF21) is a neuroprotective hormone induced by cold exposure that targets the ß-klotho co-receptor. ß-klotho is abundant in the newborn brain but decreases rapidly with age. RNA-Binding Motif 3 (RBM3) is a potent neuroprotectant upregulated by FGF21 in hypothermic conditions. We characterized serum FGF21 and RBM3 levels in patients enrolled in a prospective multi-center study of pediatric cardiac arrest (CA) via a secondary analysis of samples collected to evaluate brain injury biomarkers. Patients (n = 111) with remnant serum samples available from at least two of three available timepoints (0-24, 24-48 or 48-72 hours post-resuscitation) were included. Serum samples from 20 healthy controls were used for comparison. FGF21 was measured by Luminex and internally validated enzyme-linked immunoassay (ELISA). RBM3 was measured by internally validated ELISA. Of postarrest patients, 98 were managed with normothermia, while 13 were treated with therapeutic hypothermia (TH). FGF21 increased >20-fold in the first 24 hours postarrest versus controls (681 pg/mL [200-1864] vs. 29 pg/mL [15-51], n = 99 vs. 19, respectively, p < 0.0001, median [interquartile range]) with no difference in RBM3. FGF21 did not differ by sex, while RBM3 was increased in females versus males at 48-72 hours postarrest (1866 pg/mL [873-5176] vs. 1045 pg/mL [535-2728], n = 40 vs. 54, respectively, p < 0.05). Patients requiring extracorporeal membrane oxygenation (ECMO) postresuscitation had increased FGF21 versus those who did not at 48-72 hours (6550 pg/mL [1455-66,781] vs. 1213 pg/mL [480-3117], n = 7 vs 74, respectively, p < 0.05). FGF21 and RBM3 did not correlate (Spearman's rho = 0.004, p = 0.97). We conclude that in a multi-center study of pediatric CA patients where normothermic targeted temperature management was largely used, FGF21 was markedly increased postarrest versus control and highest in patients requiring ECMO postresuscitation. RBM3 was sex-dependent. We provide a framework for future studies examining the effect of TH on FGF21 or use of FGF21 therapy after pediatric CA.