Same Day Discharge Total Knee Arthroplasty: Hospital Demonstrates Similar Outcomes to Ambulatory Surgery Center in a More Complex Patient Population.

BACKGROUND: The purpose of this study was to compare outcomes between patients undergoing same-day discharge (SDD) total knee arthroplasty (TKA) at an ambulatory surgery center (ASC) versus a tertiary care university hospital setting. METHODS: A single tertiary academic center's institutional database was reviewed for patients that underwent primary TKA and were discharged the same day from August 2021 to January 2024. Patients who did not have at least one year of follow-up were excluded. Patient demographics, comorbidities, patient-reported outcome measures (PROMs), emergency department (ED) visits, admissions, reoperations, and revisions were collected. Patients were stratified by the location of their surgery: ASC versus hospital. Specific criteria had to be met prior to surgery at the ASC, and the final decision regarding the location of surgery was made via shared decision-making between the patient and their surgeon. Patients who did not meet ASC criteria underwent TKA at the main hospital. Univariable analyses were used to compare groups, and multivariable logistic regression was used to determine if surgical location was a significant factor. Of the 449 TKAs meeting inclusion criteria, 63.3% (284) were performed at the ASC and 36.7% (165) at the university hospital at a mean follow-up of 1.51 years (range, 1.00 to 2.40). Of those 165 whose surgery was done at the hospital, 93.9% met at least one ASC exclusion criteria. RESULTS: Patients whose TKA was done at the hospital had significantly higher weight (P = 0.003), body mass index (BMI) (P < 0.001), Elixhauser comorbidity index (ECI) (P < 0.001), proportion of patients who had an American Society of Anesthesiologists (ASA) classification of 3 (P = 0.023), and proportion of patients who required general anesthesia (P < 0.001). Additionally, patients whose TKA was done at the hospital had higher preoperative patient-reported outcome measurement information system (PROMIS) pain interference (PI) (62.0 [59.0, 66.0] versus 63.0 [61.8, 67.0]; P = 0.006), and lower physical function (PF) (39.0 [36.0, 43.0] versus 38.0 [34.0, 41.0]; P = 0.001). At 1 year, however, patients in both groups had similar PROMIS PI (53.0 [49.0, 59.0] versus 54.0 [44.0, 59.0]; P = 0.785) and PROMIS PF (47.0 [42.0, 51.0] versus 47.0 [41.0, 50.0]; P = 0422) scores as well as similar rates of achieving minimum clinically important difference (MCID) for PROMIS PI (64.4 versus 71.4%; P = 0.336) and PROMIS PF (60.5 versus 71.4%; P = 0.124). They also had a similar number of ED visits and admissions at 30 and 90 days, as well as similar reoperation-free (92.0 versus 93.3%; P = 0.79) and revision-free (95.5 versus 99.4%; P = 0.59) survival at 2 years. CONCLUSION: Although ASCs have strict patient criteria for SDD TKA, complex patients at a tertiary university hospital can be sent home the same day with equivalent outcomes. Therefore, unhealthier patients can safely achieve SDD without compromising outcomes if done in the appropriate setting.

An ecosystem of accepting life with chronic pain: A meta-ethnography.

Background: Chronic pain is a highly prevalent long-term condition, experienced unequally, impacting both the individual living with pain, and wider society. 'Acceptance' of chronic pain is relevant to improved consultations in pain care, and navigating an approach towards evidence-based, long-term management and associated improvements in health. However, the concept proves difficult to measure, and primary qualitative studies of lived experiences show complexity related to our socio-cultural-political worlds, healthcare experiences, and difficulties with language and meaning. We framed acceptance of chronic pain as socially constructed and aimed to conceptualise the lived experiences of acceptance of chronic pain in adults. Methods: We conducted a systematic search and screening process, followed by qualitative, interpretive, literature synthesis using Meta-ethnography. We included qualitative studies using chronic pain as the primary condition, where the study included an aim to research the acceptance concept. We conducted each stage of the synthesis with co-researchers of differing disciplinary backgrounds, and with lived experiences of chronic pain. Findings: We included 10 qualitative studies from Canada, Sweden, The Netherlands, Ireland, UK, Australia and New Zealand. Our 'lines of argument' include a fluid and continuous journey with fluctuating states of acceptance; language and meaning of acceptance and chronic pain, a challenge to identity in a capitalist, ableist society and the limits to individualism; a caring, supportive and coherent system. The conceptual framework of the meta-ethnography is represented by a rosebush with interconnected branches, holding both roses and thorns, such is the nature of accepting life with chronic pain. Conclusion: Our findings broaden conceptualisation of 'acceptance of chronic pain' beyond an individual factor, to a fluid and continuous journey, interconnected with our socio-cultural-political worlds; an ecosystem.

A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms.

Artificial intelligence (AI)-systems can improve cancer diagnosis, yet their development often relies on subjective histological features as ground truth for training. Here, we developed an AI-model applied to histological whole-slide images (WSIs) using CDH1 bi-allelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 bi-allelic mutations (accuracy=0.95) and diagnosed ILC (accuracy=0.96). A total of 74% of samples classified by the AI-model as having CDH1 bi-allelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and non-coding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI-model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI-algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI-models applied to WSI.

Brief Report: A population-based study of the impact of the COVID-19 pandemic on benzodiazepine use among children and young adults.

The COVID-19 pandemic was associated with increases in the prevalence of depression and anxiety among children and young adults. We studied whether the pandemic was associated with changes in prescription benzodiazepine use. We conducted a population-based study of benzodiazepine dispensing to children and young adults ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in prescription benzodiazepine dispensing occurred, and interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected benzodiazepine use. A structural break occurs where there is a sudden change in the trend of a time series. We observed an immediate decline in benzodiazepine dispensing of 23.6 per 100,000 (95% confidence interval [CI]: -33.6 to -21.2) associated with a structural break in April 2020, followed by a monthly decrease in the trend of 0.3 per 100,000 (95% CI: -0.74 to 0.14). Lower than expected benzodiazepine dispensing rates were observed each month of the pandemic from April 2020 onward, with relative percent differences ranging from - 7.4% (95% CI: -10.1% to - 4.7%) to -20.9% (95% CI: -23.2% to -18.6%). Results were generally similar in analyses stratified by sex, age, neighbourhood income quintile, and urban versus rural residence. Further research is required to understand the clinical implications of these findings and whether these trends were sustained with further follow-up.

The Trend of Medicare Reimbursement for Total Joint Arthroplasty: Using Mathematical Models to Predict Possible Per-Hour Rate Out to 2030.

Background: While multiple studies have assessed the trends of Medicare reimbursement for orthopedic total joint arthroplasty (TJA) surgeries, none have forecasted reimbursement in relatable per-hour figures. The purposes of this study are to examine trends of reimbursement for primary and revision TJA and translate forecasted primary TJA reimbursement to relatable per-hour compensation. Methods: The Center for Medicare and Medicaid Services reimbursement data from 1992 to 2024 were used to create a historical view of reimbursement for primary and revision TJA. All monetary values were converted to 2023 USD to account for inflation. Polynomial and linear forecast equations were used to predict the future of the TJA reimbursement to 2030. Relative Value Scale Update Committee standard times for procedures were used with the forecasts to establish per-hour rates. Results: Total reimbursement for primary total hip arthroplasty/total knee arthroplasty is forecasted to decrease 85.36%/86.14% by 2030. Using prior trends in reimbursement, TJA procedures are predicted to reimburse at or less than $100.00 2023 USD per Medicare case by 2030. Moreover, TJA surgeons are forecasted to earn $13.93/h per primary total hip arthroplasty and $14.97/h per primary total knee arthroplasty by 2030. Conclusions: This study highlights the concerning trends for both primary and revision arthroplasties as TJA surgeons are on a path to earn below minimum wage for primary TJAs by 2030. Mathematical models forecast a bleak future for orthopedic TJA reimbursement. This downward trajectory poses a risk to access and quality of care.

Pathophysiology of Cystic Fibrosis Liver Disease.

Hepatobiliary complications of Cystic Fibrosis (CF) constitute a significant burden for persons with CF of all ages, with advanced CF liver disease in particular representing a leading cause of mortality. The causes of the heterogeneity of clinical manifestations, ranging from steatosis to focal biliary cholestasis and biliary strictures, are poorly understood and likely reflect a variety of environmental and disease-modifying factors in the setting of underlying CFTR mutations. This review summarizes the current understanding of the pathophysiology of hepatobiliary manifestations of CF, and discusses emerging disease models and therapeutic approaches that hold promise to impact this important yet incompletely addressed aspect of CF care.

Chemokines Kill Bacteria by Binding Anionic Phospholipids without Triggering Antimicrobial Resistance.

Classically, chemokines coordinate leukocyte trafficking during immune responses; however, many chemokines have also been reported to possess direct antibacterial activity in vitro. Yet, the bacterial killing mechanism of chemokines and the biochemical properties that define which members of the chemokine superfamily are antimicrobial remain poorly understood. Here we report that the antimicrobial activity of chemokines is defined by their ability to bind phosphatidylglycerol and cardiolipin, two anionic phospholipids commonly found in the bacterial plasma membrane. We show that only chemokines able to bind these two phospholipids kill Escherichia coli and Staphylococcus aureus and that they exert rapid bacteriostatic and bactericidal effects against E. coli with a higher potency than the antimicrobial peptide beta-defensin 3. Furthermore, our data support that bacterial membrane cardiolipin facilitates the antimicrobial action of chemokines. Both biochemical and genetic interference with the chemokine-cardiolipin interaction impaired microbial growth arrest, bacterial killing, and membrane disruption by chemokines. Moreover, unlike conventional antibiotics, E. coli failed to develop resistance when placed under increasing antimicrobial chemokine pressure in vitro. Thus, we have identified cardiolipin and phosphatidylglycerol as novel binding partners for chemokines responsible for chemokine antimicrobial action. Our results provide proof of principle for developing chemokines as novel antibiotics resistant to bacterial antimicrobial resistance mechanisms.

The genomic landscape of 2,023 colorectal cancers.

Colorectal carcinoma (CRC) is a common cause of mortality1, but a comprehensive description of its genomic landscape is lacking2-9. Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome. We extend the molecular pathways involved in CRC development, define four new common subgroups of microsatellite-stable CRC based on genomic features and show that these groups have independent prognostic associations. We also characterize several rare molecular CRC subgroups, some with potential clinical relevance, including cancers with both microsatellite and chromosomal instability. We demonstrate a spectrum of mutational profiles across the colorectum, which reflect aetiological differences. These include the role of Escherichia colipks+ colibactin in rectal cancers10 and the importance of the SBS93 signature11-13, which suggests that diet or smoking is a risk factor. Immune-escape driver mutations14 are near-ubiquitous in hypermutant tumours and occur in about half of microsatellite-stable CRCs, often in the form of HLA copy number changes. Many driver mutations are actionable, including those associated with rare subgroups (for example, BRCA1 and IDH1), highlighting the role of whole-genome sequencing in optimizing patient care.

Studying the Pulmonary Endothelium in Health and Disease. An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. Endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the arterial-to-capillary-to-vein axis. While our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease.

Characterization and incidence of sunflower seed allergy in a pediatric allergy clinic.

BACKGROUND: Sunflower seeds are a popular allergen-free peanut alternative. OBJECTIVE: To describe sunflower seed allergy incidence and characteristics. METHODS: We conducted a retrospective cohort study of patients with sunflower seed allergy from 1995 to 2021 in a pediatric allergy clinic. We described demographics, testing results, atopic comorbidities, and reaction histories of patients with sunflower seed allergy, and calculated the annual cumulative incidence of the allergy. Logistic regression was used to estimate the increase in odds of sunflower seed allergy diagnosis for each year from 1995 to 2021. RESULTS: From 1995 to 2021, we identified 235 patients with sunflower seed allergy. Among patients with sunflower seed allergy, the median age at diagnosis was 3.9 years. Over three quarters of patients had another atopic condition. Half of reactions consisted of mild urticaria or rash, and a quarter met criteria for anaphylaxis. The cumulative incidence ranged from 0% (1995-1999, 2001-2004 and 2006) to 0.38% (2021). From 1995 to 2021, the odds of sunflower seed allergy diagnosis increased annually by 21% (OR 1.21, 95% CI: 1.17-1.25). CONCLUSION: In our single-center cohort of children with sunflower seed allergy, most children were diagnosed in early childhood, had high rates of comorbid atopic conditions, and had high rates of cutaneous reactions to sunflower seed products. Moreover, in our cohort, incidence of sunflower seed allergy increased.

PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases.

Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), result from an impairment of bile flow that leads to the hepatic retention of bile acids, causing liver injury. Until recently, the only approved treatments for PBC were ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). While these therapies slow the progression of PBC in the early stage of the disease, approximately 40% of patients respond incompletely to UDCA, and advanced cases do not respond. UDCA does not improve survival in patients with PSC, and patients often have dose-limiting pruritus reactions to OCA. Left untreated, these diseases can progress to fibrosis and cirrhosis, resulting in liver failure and the need for transplantation. These shortcomings emphasize the urgent need for alternative treatment strategies. Recently, nuclear hormone receptors have been explored as pharmacological targets for adjunct therapy because they regulate enzymes involved in bile acid metabolism and detoxification. In particular, the peroxisome proliferator-activated receptor (PPAR) has emerged as a therapeutic target for patients with PBC or PSC who experience an incomplete response to UDCA. PPARα is predominantly expressed in the liver, and it plays an essential role in the regulation of cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, both of which are critical enzyme families involved in the regulation of bile acid metabolism and glucuronidation, respectively. Importantly, PPARα agonists, e.g., fenofibrate, have shown therapeutic benefits in reducing elevated markers of cholestasis in patients with PBC and PSC, and elafibranor, the first PPAR (dual α, ß/δ) agonist, has been FDA-approved for the second-line treatment of PBC. Additionally, newer PPAR agonists that target various PPAR isoforms (ß/δ, γ) are under development as an adjunct therapy for PBC or PSC, although their impact on glucuronidation pathways are less characterized. This review will focus on PPAR-mediated bile acid glucuronidation as a therapeutic pathway to improve outcomes for patients with PBC and PSC.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Clinical Characteristics of Charcot-Marie-Tooth Disease Type 4J.

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by autosomal recessive variants in the Factor-Induced Gene 4 (FIG4) gene. Recent preclinical work has demonstrated the feasibility of adeno-associated virus serotype 9-FIG4 gene therapy. This study aimed to further characterize the CMT4J phenotype and evaluate feasibility of validated CMT-related outcome measures for future clinical trials. METHODS: This cross-sectional study enrolled children and adults with genetically confirmed CMT4J, with 2 documented disease-causing variants in the FIG4 gene. Patients were recruited through the Inherited Neuropathy Consortium network. Disease severity was assessed using standardized CMT-specific outcome measures and exploratory biomarkers including muscle MRI fat fraction, electrophysiology, and neurofilament light chain levels. Descriptive statistics and correlation analyses were conducted to explore relationships between variables. RESULTS: We recruited a total of 19 patients, including 14 pediatric patients (mean age 10.9 ± 3.9 years) and 5 adults (mean age 40.0 ± 13.9 years). The most frequent symptoms were gross motor delay and distal more than proximal muscle weakness, which were observed in 14 of 19 patients. The most common non-neuromuscular symptoms were cognitive and respiratory deficits, each seen in 8 of 19 patients. We denoted asymmetric weakness in 2 patients and nonuniform slowing of conduction velocities in 6 patients. Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS), Pediatric Quality of Life Inventory, and Vineland Adaptive Behavior Scale scores were affected in most patients. We observed a significant positive correlation between neurofilament light chain levels and CMTPedS, but the study was underpowered to observe a correlation between CMTPedS and MRI fat fraction. DISCUSSION: We obtained baseline clinical and biomarker data in a broad cohort with CMT4J in pediatric and adult patients. Motor delay, muscle weakness, and respiratory and cognitive difficulties were the most common clinical manifestations of CMT4J. Many patients had nerve conduction studies with nonuniform slowing, and 2 had an asymmetric pattern of muscle weakness. We observed that the neurofilament light chain levels correlated with the CMTPedS in the pediatric population. This study showed feasibility of clinical outcomes including CMTPedS in assessment of disease severity in the pediatric patient population and provided baseline characteristics of exploratory biomarkers, neurofilament light chain levels, and muscle MRI fat fraction. The coronavirus disease 2019 pandemic affected some of the visits, resulting in a reduced number of some of the assessments.

Memory compromise at extended delays in people with new-onset epilepsy.

OBJECTIVE: Memory is one of the most sensitive markers of cognitive compromise in people with new-onset epilepsy. Nonetheless, around half of these cases score within the normal range on standard memory testing. Here we explore whether memory retention at a 1-week delay reveals otherwise undetected memory compromise in such individuals, and how it relates to subjective memory complaints and mood. METHODS: Using a prospective design, 38 adults with new-onset epilepsy underwent baseline memory screening via telephone using an abbreviated Rey Auditory Verbal Learning Test (RAVLT). Psychological screening occurred via online questionnaires. One week later, without forewarning, participants completed three follow-up memory tasks. Of particular focus, we explored longer-term memory performances and forgetting trajectories in those individuals (n = 23) who demonstrated normal memory performances (scores >10th percentile) at baseline (30-min delay). Outcomes were compared to 32 healthy controls, matched for age, sex, and education. RESULTS: As a group, people with epilepsy performed worse than controls on all memory measures, with 44 percent impaired at baseline testing. Of those unimpaired at baseline, the rate and volume of information loss over 1 week was significantly greater than for controls. Contextual memory performance at 1 week was also significantly poorer for people with epilepsy. At the individual level, the prevalence of impaired forgetting was not significantly different between patients and controls. Subjective memory complaints were not related to any objective tests but were strongly related to self-reported mood and anxiety symptoms. SIGNIFICANCE: People with new-onset epilepsy show reduced memory at short and extended intervals. For those showing normal memory at baseline, information does appear to be forgotten more quickly than in healthy controls, though the effect is not large. The findings indicate that while extended delay memory testing is not essential in all new epilepsy cases, it could provide useful information for particular individuals. PLAIN LANGUAGE STATEMENT: Memory problems are common in people with epilepsy shortly after seizure onset, however, many individuals still show normal memory performances on standard neuropsychological testing. Through testing memory at an extended timepoint (1 week), our study found that on average, these individuals showed a slightly quicker rate of forgetting over a 1-week period than people without a brain condition. Self-reported memory complaints in people with new epilepsy were unrelated to their actual memory skills on testing at short and long timepoints but were rather linked to lower mood and quality of life.

'You can be as vigilant as you can, yet they make their way in': A descriptive study of parent and caregiver perspectives towards keeping children safe from button batteries.

Objectives: Button batteries pose a significant threat to young children, and parents and caregivers play an important role in keeping children safe from button batteries, especially in the home environment. However, little is known regarding parent or caregiver perspectives on button battery safety, in particular, the threat they pose to children. The aim of this study was to examine perspectives on button battery safety to enable tailored prevention strategies and to examine parent and caregiver perspectives on button battery safety in the home. Methods: One hundred and seventy-four parents and caregivers of children aged 0-5 completed a cross-sectional online survey. Distribution occurred via social media. The survey contained multiple-choice questions pertaining to button battery knowledge and attitudes. Results: Most respondents recognised the dangers of button battery ingestion, yet only 37% knew of button battery ingestion symptoms. While 68% knew of household items containing button batteries, 21% were aware of product-recall information sources. Approximately 64% understood immediate post-ingestion steps, but only 31% were familiar with first-aid procedures. From an attitudinal standpoint, 95% understood the importance of child supervision around button batteries, 78% prioritised battery safety in toy purchases, and 17% found current safety labels unsatisfactory. This study provides a foundation for ongoing investigation of parent and caregiver perspectives on button battery home safety. Conclusion: Ongoing, comprehensive education and public-safety campaigns are needed to rectify gaps in knowledge regarding button battery safety, and to reduce the risk of button battery ingestion in children.

Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score.

We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.