Campus source to sink wastewater surveillance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Wastewater-based surveillance (WBS) offers an aggregate, and cost-effective approach for tracking infectious disease outbreak prevalence within communities, that provides data on community health complementary to individual clinical testing. This study reports on a 16-month WBS initiative on a university campus in England, UK, assessing the presence of SARS-CoV-2 in sewers from large buildings, downstream sewer locations, raw wastewater, partially treated and treated effluents. Key findings include the detection of the Alpha (B.1.1.7) variant in wastewater, with 70 % of confirmed campus cases correlating with positive wastewater samples. Notably, ammonium nitrogen (NH4-N) levels showed a positive correlation (ρ = 0.543, p < 0.01) with virus levels at the large building scale, a relationship not observed at the sewer or wastewater treatment works (WWTW) levels due to dilution. The WWTW was compliant to wastewater standards, but the secondary treatment processes were not efficient for virus removal as SARS-CoV-2 was consistently detected in treated discharges. Tools developed through WBS can also be used to enhance traditional environmental monitoring of aquatic systems. This study provides a detailed source-to-sink evaluation, emphasizing the critical need for the widespread application and improvement of WBS. It showcases WBS utility and reinforces the ongoing challenges posed by viruses to receiving water quality.

Pediatric Heart Transplantation Over 36 Years and Contemporary Volume-Outcome Analysis of UNOS.

BACKGROUND: This study examines 36 years of national pediatric heart transplantation data to 1) identify trends in transplant volume, centers, and one-year graft survival, and 2) assess how center transplant volume impacts outcomes over a contemporary 11-year period. METHODS: We performed a retrospective review of pediatric patients (<18 years) undergoing heart transplantation from 1/1/1987 to 12/31/2022 using the United Network for Organ Sharing Database. Trend analyses included the whole cohort, while volume-outcome analyses included a contemporary cohort to account for the temporal changes observed in transplant survival. Highest volume centers were defined by the number of heart transplants performed per center per year. RESULTS: Over 36 years, 11,828 pediatric heart transplants were performed. Transplant volume steadily rose, the number of centers remained stable, and one-year graft survival has improved significantly. In the contemporary era (2012-2022), 89 centers conducted 4,959 pediatric heart transplants. The top 15% high-volume centers (13 centers) accounted for 48.3% (2,393) of transplants, with an average of 16.7±3.8 transplants per center annually, compared to 3.9±3.1 for lower volume centers. Despite transplanting higher risk patients, high-volume centers had similar postoperative outcomes and improved long-term survival. CONCLUSIONS: While the number of US pediatric heart transplant centers has remained stable, pediatric heart transplant volume is steadily increasing, as is one-year graft survival. In a contemporary cohort, the top 15th percentile highest volume centers accounted for 48.3% of US pediatric heart transplants and transplanted higher risk patients with similar postoperative outcomes and improved longitudinal survival.

Outcomes of Isolated Tricuspid Valve Surgery: A Society of Thoracic Surgeons Analysis and Risk Model.

BACKGROUND: To provide patients and surgeons with clinically relevant information, the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS-ACSD) was queried to develop a risk model for isolated tricuspid valve (TV) operations. METHODS: All patients in the STS-ACSD undergoing isolated TV repair or replacement (N=13,587; age 48.3±18.4 years) were identified (7/2017-6/2023). Multivariable logistic regression accounting for TV replacement versus repair was used to model eight operative outcomes: mortality, morbidity and/or mortality, stroke, renal failure, reoperation, prolonged ventilation, short and prolonged hospital stay. Model discrimination (C-statistic) and calibration were assessed using 9-fold cross-validation. RESULTS: The isolated TV study population included 41.1% repairs (N=5,583; age 52.6±18.1 years) and 58.9% replacements (N=8,004; age 45.3±18.0 years). Overall predicted risk of operative mortality was 5.6%, similar in repairs and replacements (5.5% and 5.7%, respectively); as was the predicted risk of composite morbidity and mortality (28.2% and 26.8%). Replacements were generally younger patients with a higher endocarditis prevalence than repairs (45.7% vs. 21.1%). The model yielded a C-statistic of 0.81 for mortality and 0.76 for the composite of morbidity and mortality, with excellent observed-to-expected calibration that was comparable in all sub-cohorts and predicted risk decile groups. CONCLUSIONS: A new STS risk model has been developed for isolated TV surgery. The current mortality of isolated TV operations is lower than previously observed. This risk prediction model and these contemporary outcomes provide a new benchmark for current and future isolated TV interventions.

Combined en bloc heart and liver organ procurement.

A combined heart+liver transplant is the only option for survival in some patients with end-stage combined cardiac and hepatic disease. These patients may suffer from congenital or acquired cardiac disease. The potential aetiologies of the associated hepatic disease are heterogeneous and include systemic disease that impacts the liver as well as venous congestion in patients with functionally univentricular circulation. In the latter scenario, patients with functionally univentricular circulation often require complex cardiac reconstruction in the setting of a cardiac transplant after staged palliation. During cardiac procurement, our approach is to dissect the entire ascending aorta and aortic arch in continuity; the entire superior caval vein and innominate vein in continuity; and the pulmonary arteries from hilum to hilum if the donor is not a candidate for recovery of the lungs. The cardiac and abdominal organ procurement teams work in parallel during dissection and combined en bloc cardio-hepatectomy. This technique minimizes exposure of both organs to cold ischaemia. This video tutorial demonstrates the key steps for combined en bloc heart+liver organ procurement.

An Expanded Approach to the Ascertainment of Children and Youth With Special Health Care Needs.

OBJECTIVE: To describe the prevalence, characteristics, and health-related outcomes of children with diagnosed health conditions and functional difficulties who do not meet criteria for having a special health care need based on the traditional scoring of the Children with Special Health Care Needs (CSHCN) Screener. METHODS: Data come from the 2016 to 2021 National Survey of Children's Health (n = 225 443). Child characteristics and health-related outcomes were compared among 4 mutually exclusive groups defined by CSHCN Screener criteria and the presence of both conditions and difficulties. RESULTS: Among children who do not qualify as children and youth with special health care needs (CYSHCN) on the CSHCN Screener, 6.8% had ≥1 condition and ≥1 difficulty. These children were more likely than CYSHCN to be younger, female, Hispanic, uninsured, privately insured, living in a household with low educational attainment, have families with more children and a primary household language other than English. After adjustment, non-CYSHCN with ≥1 conditions and ≥1 difficulty were less likely than CYSHCN, but significantly more likely than other non-CYSHCN, to have ≥2 emergency department visits, have unmet health care needs, not meet flourishing criteria, live in families that experienced child health-related employment impacts and frustration accessing services. Including these children in the calculation of CYSHCN prevalence increases the national estimate from 19.1% to 24.6%. CONCLUSIONS: Approximately 4 million children have both a diagnosed health condition and functional difficulties but are not identified as CYSHCN. An expanded approach to identify CYSHCN may better align program and policy with population needs.

Spatial Resolution Fidelity Comparison Between Energy Integrating and Deep Silicon Photon Counting CT: Implications for Pulmonary Imaging.

PURPOSE: We investigated spatial resolution loss away from isocenter for a prototype deep silicon photon-counting detector (PCD) CT scanner and compare with a clinical energy-integrating detector (EID) CT scanner. MATERIALS AND METHODS: We performed three scans on a wire phantom at four positions (isocenter, 6.7, 11.8, and 17.1 cm off isocenter). The acquisition modes were 120 kV EID CT, 120 kV high-definition (HD) EID CT, and 120 kV PCD CT. HD mode used double the projection view angles per rotation as the "regular" EID scan mode. The diameter of the wire was calculated by taking the full width of half max (FWHM) of a profile drawn over the radial and azimuthal directions of the wire. Change in wire diameter appearance was assessed by calculating the ratio of the radial and azimuthal diameter relative to isocenter. t tests were used to make pairwise comparisons of the wire diameter ratio with each acquisition and mean ratios' difference from unity. RESULTS: Deep silicon PCD CT had statistically smaller (P<0.05) changes in diameter ratio for both radial and azimuthal directions compared with both regular and HD EID modes and was not statistically different from unity (P<0.05). Maximum increases in FWMH relative to isocenter were 36%, 12%, and 1% for regular EID, HD EID, and deep silicon PCD, respectively. CONCLUSION: Deep silicon PCD CT exhibits less change in spatial resolution in both the radial and azimuthal directions compared with EID CT.

Improvement of tumor neoantigen detection by high field asymmetric waveform ion mobility mass spectrometry.

Cancer neoantigens have been shown to elicit cancer-specific T-cell responses and have garnered much attention for their roles in both spontaneous and therapeutically induced antitumor responses. Mass spectrometry (MS) profiling of tumor immunopeptidomes has been used, in part, to identify MHC-bound mutant neoantigen ligands. However, under standard conditions, MS-based detection of such rare but clinically relevant neoantigens is relatively insensitive, requiring 300 million cells or more. Here, to quantitatively define the minimum detectable amounts of therapeutically relevant MHC-I and MHC-II neoantigen peptides, we analyzed different dilutions of immunopeptidomes isolated from the well-characterized T3 mouse methylcholanthrene (MCA)-induced cell line by MS. Using either data-dependent acquisition (DDA) or parallel reaction monitoring (PRM), we established the minimum amount of material required to detect the major T3 neoantigens in the presence or absence of high field asymmetric waveform ion mobility spectrometry (FAIMS). This analysis yielded a 14-fold enhancement of sensitivity in detecting the major T3 MHC-I neoantigen (mLama4) with FAIMS-PRM compared with PRM without FAIMS, allowing ex-vivo detection of this neoantigen from an individual 100 mg T3 tumor. These findings were then extended to two other independent MCA-sarcoma lines (1956 and F244). This study demonstrates that FAIMS substantially increases the sensitivity of MS-based characterization of validated neoantigens from tumors.

A computational neural model that incorporates both intrinsic dynamics and sensory feedback in the Aplysia feeding network.

Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding.

Sufficient COVID-19 quarantine and testing on international travelers to forestall cross-border transmission after China's removal of the Zero-COVID policy in early 2023.

BACKGROUND: Removal of zero-COVID restrictions in China led to a surge in COVID-19 cases. In response, countries imposed restrictions on Chinese travelers. However, border policies imposed may not have been informed by accurate data and may not have provided substantial benefits. METHODS: We analyzed quarantines sufficient to prevent additional in-country transmission for February 13-19, 2023 based on World Health Organization (WHO) and self-reported infection rates to estimate prevalence. RESULTS: We have shown that self-reported prevalence data indicated more stringent border restrictions compared to WHO-published prevalence statistics. No travel restrictions were required for Singapore, South Korea, and Japan so that infections would not be greater than with complete border closure. However, a 1-day, 2-day, and 3-day quarantine were indicated for England, Germany, and Scotland respectively. A 10-day, 13-day, and 14-day quarantine were required for Italy, France, and the Philippines, respectively, to prevent an increase in within-country infections due to travel. Vietnam and Thailand required a complete border shutdown. CONCLUSIONS: Our results demonstrated the necessity for accurate and timely reporting of pandemic statistics to prevent an increase in viral spread. Through the minimum-quarantine analysis, countries can use science to determine policy, minimize international friction, and improve the cost-efficiency of interventions.

Dermatologic manifestations of hereditary hemochromatosis: A systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

Endoluminal Biopsy for Vein of Galen Malformation.

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

Phylogenomic perspectives on speciation and reproductive isolation in a North American biodiversity hotspot: An example using California sages (Salvia subg. Audibertia; Lamiaceae).

BACKGROUND AND AIMS: The California Floristic Province (CA-FP) is the most species-rich region of North America north of Mexico. One of several proposed hypotheses explaining the exceptionally diversity of the region is that the CA-FP harbors myriad recently diverged lineages with nascent reproductive barriers. Salvia subgenus Audibertia is a conspicuous element of the CA-FP, with multiple sympatric and compatible species. METHODS: Using 305 nuclear loci and both organellar genomes, we reconstruct species trees, examine genomic discordance, conduct divergence-time estimation, and analyze contemporaneous patterns of gene flow and mechanical reproductive isolation. KEY RESULTS: Despite strong genomic discordance, an underlying bifurcating tree is supported. Organellar genomes capture additional introgression events not detected in the nuclear genome. Most interfertility is found within clades, indicating that reproductive barriers are coincident with genetic divergence. Species are generally not mechanically isolated, suggesting that it is unlikely to be the primary factor leading to reproductive isolation. CONCLUSIONS: Rapid, recent speciation with some interspecific gene flow in conjunction with the onset of a Mediterranean-like climate is the underlying cause of extant diversity in Salvia subgenus Audibertia. Speciation has largely not been facilitated by gene flow. Its signal in the nuclear genome seems to mostly be erased by backcrossing, but organellar genomes each capture different instances of historical gene flow, likely characteristic of many CA-FP lineages. Mechanical reproductive isolation appears to be only part of a mosaic of factors limiting gene flow.

Structural transitions enable interleukin-18 maturation and signaling.

Several interleukin-1 (IL-1) family members, including IL-1ß and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

Utility of IL-36 immunostaining in distinguishing psoriasis from pityriasis rosea and pityriasis lichenoides.

BACKGROUND: Psoriasis is an inflammatory skin disease driven by upregulation of cytokines in the Th17 pathway, including interleukin-36 (IL-36). Previous studies have highlighted the utility of IL-36 immunostaining for psoriasis compared to spongiotic dermatitis and other psoriasiform dermatoses; however, no study has examined the role of IL-36 staining in distinguishing psoriasis from pityriasis rosea (PR) and pityriasis lichenoides (PL), known histologic mimickers of psoriasis. METHODS: We compared the immunostaining pattern of IL-36 for 21 PR cases, 22 PL cases, and 10 psoriasis cases. We graded the immunostaining as 0, negative; 1, focal weak; 2, diffuse weak; 3, focal, strong; or 4, diffuse strong. We further categorized stains as negative (0-2 score) or positive (3-4 score) and utilized Fisher's exact test to compare the immunostaining pattern of these entities. RESULTS: All psoriasis specimens were positive for IL-36, whereas all PR specimens were negative (p = 0.00000002). Twenty PL specimens were negative (p = 0.000001). Nine of 10 pityriasis lichenoides et varioliformis acuta cases were negative (p = 0.00012), and 11 of 12 cases of pityriasis lichenoides chronica were negative (p = 0.00003). CONCLUSIONS: Our findings highlight the potential role of IL-36 immunostaining in distinguishing psoriasis from other psoriasiform dermatoses, including PR and PL.

Development and Initial Validation of a Meniere's Disease Quality of Life Instrument: The MenQOL.

OBJECTIVE: To design and validate a disease-specific quality of life instrument for Meniere's disease. METHODS: We used a sequential process of expert input, patient focus groups, and analyses of responses to draft questionnaires to create a 24-item Meniere's disease quality of life (MenQOL) instrument. The MenQOL and the SF-36v2 were administered to a cohort of 50 patients with Meniere's disease and 60 comparison patients with tinnitus, vertigo, or hearing loss from other causes identified at a tertiary academic center. We performed exploratory factor analysis, Cronbach's α, between group comparisons of total MenQOL scores, and regression analyses between the MenQOL and SF-36v2 to evaluate the instrument's factor structure, internal consistency, face validity, and external validity. Segregation of the instrument into domains was assessed by exploratory factor analysis. RESULTS: Exploratory factor analysis revealed that the MenQOL has a single domain. Cronbach's α = 0.914 indicated high internal consistency for the instrument as a whole. Mean MenQOL scores showing significantly worse quality of life among patients with Meniere's disease than comparison participants (52.5 ± 15.8 vs. 43.2 ± 12.6; p = 0.0051), indicating good construct validity. Significant inverse relationships in bivariate linear regressions between total MenQOL scores and SF-36v2 physical (slope = -0.94, p < 0.0001) and mental (slope = -1.16, p < 0.0001) composite scores showed acceptable concurrent validity. CONCLUSIONS: We have described the initial development of the MenQOL, a simple, valid patient-reported outcome measure that, subject to further study, may be used to assess the effects of treatment on disease-specific quality of life in patients with Meniere's disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Gambian Mothers Lack Obstetric Danger Sign Knowledge, But Educational Intervention Shows Promise.

Background: The Gambia has the 12th highest maternal mortality rate in the world, with 80% of deaths resulting from avoidable causes. Unawareness of pregnancy danger signs (DS) has been shown to be a barrier to seeking obstetric care, while app-based education intervention has shown promise. Objective: We aim to assess patient awareness of DS, identify barriers to awareness, and evaluate potential for implementing smartphone-based technologies for education. Methods: A cross-sectional semi-structured survey was administered to Gambian women (n = 100) across five hospitals/health centers. Data and informed consent were collected via an online survey portal. Analysis included bivariate analysis and descriptive statistics with p < 0.05 significance level. Recall of 0-2 DS per category was classified as "low" knowledge, 3-5 as "moderate" knowledge, and 6+ as "sufficient" knowledge. Cross-category recall was quantified for overall awareness level (0-6 = "low", 7-12 = "moderate", 13+ = "sufficient". N = 28 total DS). Findings: Although 75% of participants (n = 100) self-perceived "sufficient" knowledge of DS, the average recall was only two (SD = 2, n = 11) pregnancy DS, one labor and delivery DS (SD = 1, n = 8), and one postpartum DS (SD = 1, n = 9). Twenty-one women were unable to recall any danger signs. "Low" awareness was identified in 77% of women, while 23%, and 0% of women showed "moderate" and "sufficient" overall awareness, respectively. Education level was significantly correlated with overall danger sign recall (ρ(98) = .243, p = .015) and awareness level (ρ(98) = .265, p = .008). Monthly income was significantly correlated with awareness level (ρ(97) = .311, p = .002). Smartphone ownership was reported by 76% of women, and 97% expressed interest in using app-based video (94%) or provider (93%) teaching. Conclusions: Women had low knowledge of obstetric danger signs, and true awareness of danger signs was remarkably lower than self-perceived knowledge. However, patients exhibited proper healthcare-seeking behavior when danger signs arose. Findings suggest that video- or messaging-based education from local healthcare providers may be effective DS educational interventions.

Predicting Stroke For Pediatric Patients Supported With Ventricular Assist Devices:A PEDIMACS Report.

BACKGROUND: PEDIMACS provides detailed understanding on pediatric patients supported with ventricular assist devices (VADs). We sought to identify important variables affecting the incidence of stroke in pediatric VADs. METHODS: Between 2012-2022, 1,463 devices in 1,219 patients were reported to PEDIMACS s from 40 Centers in patients<19yrs at their first VAD implantation. Multiphase parametric hazard modeling was used to identify risk factors for stroke among all device types. RESULTS: Of the 1,219 patients, the most common devices were implantable continuous (472 [39%]), followed by paracorporeal pulsatile (342 [28%]), paracorporeal continuous (327 [27%]). Overall freedom from stroke at 6 months was higher in the recent era (2012-2016; 80.2% [77.1%-82.9%] vs 2017-2023; 87.9% [86.2%-89.4%], p=0.009). Implantable Continuous had the highest freedom from stroke at 3 (92.7% [91.1%-93.9%]) and 6 (91.1% [89.3%-92.6%]) months, followed by Paracorporeal Pulsatile (87.0% [84.8%-88.9%] and 82.8% [79.8%-85.5%]), and Paracoporeal Continuous (76.0% [71.8%-79.5%] and 69.5% [63.4%-74.8%]). Parametric modeling identified risk factors for stoke early post implant and later. Overall, and particularly for Paracorporal Pulsatile devices, early stroke risk has decreased in the most recent era (HR 5.01). Among Implantable Continuous devices, cardiogenic shock was the major risk factor. For patients<10kg, early hazard was only seen in previous era. For congentail patients, early hazard was seen in non-implantable device use and use of ECMO. CONCLUSIONS: Overall stroke rate has decreased from 20% to 15% at 6 months, with particular improvement among PP devices. Risk factor analyses offer insights for identification of higher stroke risk subsets and further management refinements.