Noninvasive Surveillance Research Articles

NIMG-50. MULTIPARAMETRIC MRI DISTINGUISHES NEURONAL AND IMMUNE SIGNATURES IN INVASIVE HIGH-GRADE GLIOMA RIM THROUGH GRAPH NETWORK ANALYSIS

Abstract BACKGROUND Standard of care surgery for high grade glioma (HGG) employs Magnetic Resonance Imaging to identify the contrast enhancing (CE) core for resection, leaving a non-enhancing (NE) invasive rim of tumor which contributes to recurrence. Multi-parametric MRI (mpMRI) has recently been used to map regional biological heterogeneity of neuronal and immune signatures in HGG, and continues to offer a promising strategy for non-invasive surveillance of tumor progression. Here, we present a graph network analysis relating mpMRI to biological signatures in the NE tumor rim and show the utility of communities of imaging features for discriminating tumor phenotypes. METHODS 53 mpMRI features across 101 spatially-localized RNA-sequenced biopsy samples from 64 patients with IDH-wt HGG were represented as nodes within a Neo4j graph network. Modularity optimization was used to identify communities of densely connected nodes. Communities of nodes representing high proportions of NE samples (one-tailed test) were kept for further analysis. Gene set enrichment analysis (GSEA) on samples within selected imaging communities was analyzed for biological process enrichment using clusterProfiler. Single sample GSEA (ssGSEA) using ssGSEA2 was used to annotate neuronal and immune cell states across samples within selected communities. mpMRI feature selection within each community identified the most relevant imaging features for isolating samples classified into neuronal and immune cell states. RESULTS 11 imaging communities gathered a high proportion of NE samples. Three NE communities showed significant enrichment of neuronal signatures, while one showed significant enrichment of immune pathways. One neuronal-predominant community showed unique upregulation of 14 pathways related to neuronal migration/astrocyte projection. CONCLUSION Network imaging communities can identify clusters of NE glioma samples showing contrasting neuronal and immune signatures, including distinct upregulation of migration and projection pathways. Mapping these imaging feature communities to specific biological processes implicated in glioma progression may aid treatment planning and prognostication for glioma patients.

Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real-World Analysis of Donor-Derived Cell-Free DNA-Based Surveillance Protocol.

Acute cellular (ACR) and antibody-mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor-derived cell-free DNA (dd-cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd-cfDNA in screening for acute rejection (AR) and donor-specific antibodies (DSAs) in pediatric HT recipients. Blood samples for dd-cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0-150 days), and presence of DSAs. There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd-cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd-cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%-11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd-cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%. Implementation of noninvasive rejection surveillance with dd-cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long-term monitoring of allograft health in pediatrics.

Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics.

Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration-based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.

Association Between High Sensitivity Troponin I and NTproBNP With Rejection and Graft Loss in Pediatric Heart Transplant Recipients.

Troponin I is a blood biomarker of cardiac injury and levels measured using a high-sensitivity assay after pediatric heart transplantation (HT) have not been described. We sought to assess the association between high-sensitivity troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NTproBNP) with treated acute rejection (AR) and graft loss in pediatric heart transplant (HT) recipients. Serum was collected and banked from pediatric HT recipients prior to cardiac catheterization. Patients with samples drawn within 365 days post-HT were included and followed for up to 5 years. Generalized linear mixed-effect models examined the association between hsTnI and treated AR using a random intercept per patient. Cox proportional hazards models tested the association between maximal hsTnI and NT-proBNP and death/graft loss. HsTnI and NTproBNP values decline in the weeks following HT, after which these biomarkers stabilize. HsTnI was higher in AR versus no AR (6.2 vs. 3.5 ng/L, p < 0.001); doubling of hsTnI increased the odds of AR by 33% (p = 0.004). HsTnI showed moderate discrimination for AR with an AUC of 0.811 (95% CI 0.76, 0.87) and a NPV of 96.4% (95% CI 93.0, 98.1). Elevation in NT-proBNP was not associated with AR. In multivariable Cox modeling, a doubling of maximal NT-proBNP was associated with graft loss (HR 8.96, p = 0.014). In this pediatric HT cohort, HsTnI was moderately discriminative for AR and higher maximal NT-proBNP was associated with graft loss. HsTnI may add value in pediatric HT non-invasive AR surveillance, and elevated NTproBNP could suggest an increased risk of graft loss.

Analysis of urine cell-free DNA in bladder cancer diagnosis by emerging bioactive technologies and materials.

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

Vectorcardiography Predicts Heart Failure in Patients Following ST Elevation Myocardial Infarction.

Modeling outcomes, such as onset of heart failure (HF) or mortality, in patients following ST elevation myocardial infarction (STEMI) is challenging but clinically very useful. The acute insult following a myocardial infarction and chronic degeneration seen in HF involve a similar process where a loss of cardiomyocytes and abnormal remodeling lead to pump failure. This process may alter the strength and direction of the heart's net depolarization signal. We hypothesize that changes over time in unique parameters extracted using vectorcardiography (VCG) have the potential to predict outcomes in patients post-STEMI and could eventually be used as a noninvasive and cost-effective surveillance tool for characterizing the severity and progression of HF to guide evidence-based therapies. We identified 162 patients discharged from Michigan Medicine between 2016 and 2021 with a diagnosis of acute STEMI. For each patient, a single 12-lead ECG > 1 week pre-STEMI and > 1 week post-STEMI were collected. A set of unique VCG parameters were derived by analyzing features of the QRS complex. We used LASSO regression analysis incorporating clinical variables and VCG parameters to create a predictive model for HF, mortality, or the composite at 90, 180, and 365 days post-STEMI. The VCG model is most predictive for HF onset at 90 days with a robust AUC. Variables from the HF model mitigating or driving risk, at a p < 0.05, were primarily parameters that assess the area swept by the depolarization vector including the 3D integral and convex hull in select spatial octants and quadrants.

Noninvasive rejection surveillance after solid organ transplantations: analysis of the donor-derived cell-free DNA

A szolidszerv-transzplantátum kilökődése a modern immunszuppresszív kezelés mellett is a graftdiszfunkció, a hospitalizáció és a halálozás egyik fő etiológiai tényezője. A rejekció diagnosztikájában ’gold standard’ invazív biopszia azonban a hospitalizáció mellett számos szövődménnyel járhat, interpretálását nagy interobszerver variabilitás jellemzi. A rejekció megítélésében a noninvazív módszerek ezért nagy klinikai jelentőséggel bírnak. A graftkárosodást jellemző donoreredetű sejtmentes DNS (dd-cfDNA) a recipiens szérumából mutatható ki, szintje már a biopszia által igazolt kilökődést megelőzően emelkedést mutat, és magas negatív prediktív értékkel bír. Munkánk során a dd-cfDNA-assay szolid szerv (vese, máj, szív, tüdő, hasnyálmirigy) transzplantációját követően betöltött szerepét vizsgáltuk az elérhető irodalom összefoglalásával, továbbá a szívtranszplantáltak körében a rutin klinikai gyakorlatba 2022. októberben bevezetett dd-cfDNA-alapú rejekció utánkövetése során nyert első hazai eredményeinket kívánjuk megosztani. Cardialis allograftrejekció utánkövetése során 46 szívtranszplantált beteg 264 dd-cfDNA-mintáját elemeztük. Az eredmény a keringő donoreredetű sejtmentes DNS és a plazma teljes (recipiens- és donoreredetű) sejtmentes DNS arányát mutatja: a ≥0,20% dd-cfDNA-érték károsodásra, míg a ≥0,35% dd-cfDNA-szint súlyos graftkárosodásra utal. A dd-cfDNA-minták 80%-a &lt;0,20% értéket mutatott. Myocardium-károsodásra utaló dd-cfDNA-érték következtében összesen 20 szívizom-biopsziát végeztünk: kilökődés 6 esetben igazolódott. 16 hónap során 232, a reguláris surveillance-biopsziák 88%-a biztonságosan elhagyható volt a dd-cfDNA-értékek alapján. A korai graftkárosodás kimutatása által lehetőség nyílik az immunszuppresszív terápia korai és személyre szabott módosítására a súlyosabb fokú kilökődés és az irreverzibilis graftkárosodás megelőzése, illetve a gyógyszertoxicitás elkerülése érdekében. Orv Hetil. 2024; 165(33): 1275–1285.

Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry

BackgroundMolecular testing with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual non-invasive surveillance on clinical decision-making has not been widely investigated. MethodsWe evaluated 2077 subjects from the SHORE registry who were enrolled between 2018 and 2021 and had verified biopsy data, and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. Incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LR+) were calculated and biopsy rates over time were analyzed. ResultsThe incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive and 9.2% for dual positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive and 35.4% for dual positive results. The LR+ for ACR was 1.37, 2.91 and 3.90 for GEP positive, dd-cfDNA positive and dual positive testing, respectively. From 2018-2021, first-year biopsy rates declined from 5.9 to 5.3 biopsies/patient, and second year from 1.5 to 0.9 biopsies/patient. At two-years, survival was 94.9% and only 2.7% had graft dysfunction. ConclusionsDual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. Use of dual non-invasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.

Non-invasive surveillance of shared pathogens in the Eurasian brown bear (Ursus arctos) human interface

Multi-host communities are perfect scenarios for the emergence and spread of pathogens, threatening the recovery of endangered, isolated, or inbred populations, such as the brown bear (Ursus arctos) in northwestern Spain. The population recovery in recent years has forced bears to occupy highly anthropized areas, increasing their interaction with human and domestic animals, with potential consequences for global health. During 2022–2023 a survey of parasites, bacteria and viruses shared between wildlife, domestic animals and humans was performed in this population using non-invasive surveillance, i.e., bear fecal samples (n = 73) and sponge-based sampling of trees (n = 42; 14 rubbed trees and 28 control trees). Pathogen detection rates were defined as the percentage of qPCR or culture-positive samples. Generalized linear models were fitted to assess their relationship with environmental variables including dispersion of the human population, and percentage of agricultural and periurban habitats in a 6 km-buffer around each sample. Canine Adenovirus type 1 (45.2%), Giardia spp. (15.1%), Salmonella spp. (12.3%), and extended-spectrum-beta-lactamases (ESBL) Escherichia coli (1.4%) were identified in fecal samples. In contrast, only five sponges from three rubbed and two control trees resulted positive to E. coli (14.3%). The results suggest that several pathogens are common in the Cantabrian brown bear population and that anthropization of the territory modulates their prevalence and richness.The effective design of management programs for bear conservation will require a one-health approach, in which genetic analysis of non-invasive samples can be key tools for the sanitary surveillance at the wildlife-livestock-human interface.

Remote Surveillance Technology of Dialysis Arteriovenous Access: Retrospective Evaluation in a UK Renal Centre

Background: Early identification of dysfunctional arteriovenous haemodialysis (HD) vascular access (VA) is important for timely referral and intervention. Method: We retrospectively calculated VA risk score using Vasc-Alert surveillance software technology from HD treatment sessions in 2 satellite HD units over 18 months. We included in the analysis HD patients dialysing with arteriovenous fistula or graft (AVF/G) with available Vasc-Alert data for≥ 2 months. For group one (eventful) that included patients who developed vascular access thrombosis or stenosis over the study period, we collected Vasc-Alert risk score 2 months prior to the event and, for group two (uneventful), over 5 consecutive months. Vasc-Alert technology utilises routinely collected data during HD to calculate VA risk score and triggers an alert if the score is ≥7 in 3 consecutive dialysis sessions. Patients with >2 alerts (vascular access score ≥7) per month were considered to have positive alerts. Results: From 140 HD patients, 81 patients dialysed via AVF/G. 77/81 had available Vasc-Alert data and were included in the final analysis. Out of 17 eventful patients, 11 (64.7%) had positive alerts 2 months prior to the vascular event. Out of the 60 patients without vascular events, 20 patients (33.3%) had positive alert. Vasc-Alert’s sensitivity and specificity for vascular events were 64.7% and 66.6%, respectively. Within the 6 patients with thrombosed access, 2 patients (33.3%) detected by Vasc-Alert were not detected with clinical monitoring. Conclusion: Vascular access risk score can be a useful non-invasive vascular access surveillance method to assist clinical decision making.

DEMA: A Deep Learning-Enabled Model for Non-Invasive Human Vital Signs Monitoring Based on Optical Fiber Sensing.

Optical fiber sensors are extensively employed for their unique merits, such as small size, being lightweight, and having strong robustness to electronic interference. The above-mentioned sensors apply to more applications, especially the detection and monitoring of vital signs in medical or clinical. However, it is inconvenient for daily long-term human vital sign monitoring with conventional monitoring methods under the uncomfortable feelings generated since the skin and devices come into direct contact. This study introduces a non-invasive surveillance system that employs an optical fiber sensor and advanced deep-learning methodologies for precise vital sign readings. This system integrates a monitor based on the MZI (Mach-Zehnder interferometer) with LSTM networks, surpassing conventional approaches and providing potential uses in medical diagnostics. This could be potentially utilized in non-invasive health surveillance, evaluation, and intelligent health care.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Role of Cerebroplacental Ratio in Predicting Perinatal Outcome.

Objective Doppler velocimetry provides a sensitive, non-invasive, and safe method of surveillance of fetal hemodynamics and fetomaternal circulation. Cerebroplacental ratio (CPR) is an indicator of placental function and fetal maladaptation to placental insufficiency. Cerebroplacental ratio (CPR) is becoming a significant indicator of unfavorable pregnancy outcomes, which has implications for the assessment of fetal well-being. This study aimedto determine the cut-off value of the cerebroplacental ratio (CPR) in appropriate for gestational age (AGA) fetuses in high-risk mothers to predict adverse perinatal outcomes. We also compared the efficacy of CPR, umbilical artery pulsatility index (UmA PI), and middle cerebral artery pulsatility index (MCA PI) for predicting adverse perinatal outcomes. Design and setting This was a prospective observational study conducted at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Methods A total of 100 women with singleton high-risk pregnancies were included in this prospective observational study. Obstetric ultrasound was performed at the time of recruitment, and fetal weight and CPR were noted. Based on fetal weight, patients were divided into AGA and fetal growth restriction (FGR) groups; CPR was measured; patients were followed up fortnightly; and outcomes were noted. Main outcome The effectiveness of CPR, UmA PI, and MCA PI for predicting poor perinatal outcomes and identifying the cut-off value of CPR in appropriate for gestational age (AGA) fetuses in high-risk mothers was assessed. Result The values of MCA PI, UmA PI, and CPR were statistically significant between AGA and FGR (p-value =.023, .002 and .0001), respectively. The cut-off value for CPR-detecting adverse outcomes in AGA was 1.49. It has sensitivity, specificity, positive predictive value, and negative predictive value of 67.5%, 68%, 71.69%, and 70.21%, respectively. Conclusion Cerebroplacental ratio (CPR) reflects both circulatory insufficiency of the placenta and adaptive changes of the middle cerebral artery, indicating an important non-invasive surveillance modality.

FibroScan as a surveillance marker post-cavopulmonary anastomosis for single-ventricle physiology.

Single-ventricle physiology encompasses a group of congenital cardiac malformations with only one functional ventricle. The Fontan procedure is the final palliation of this pathway and has its complications. One of these is Fontan-associated liver disease (FALD). It is known that all patients with Fontan will have FALD, due to the physiology of the Fontan circuit, and only the severity will vary. The pathophysiology of hepatic damage in FALD is unique and not easily detectable by routine non-invasive investigations. Therefore, this study is aimed to identify if FibroScan can be used as a surveillance marker to detect and assess the progression of FALD. Patients who attended the Cardiothoracic and Vascular Surgery Outpatient Department (OPD) for follow-up post-cavopulmonary anastomosis (bidirectional Glenn and Fontan) were enrolled in this study. They underwent routine examinations and tests, and in addition a FibroScan was performed. FibroScan showed that the liver stiffness measurement (LSM) was increased in all patients who had undergone Fontan and a couple of patients who had undergone bidirectional (BD) Glenn. The LSM was 12.29 (± 3.59) kPa in patients post-Fontan and 6.64 (± 4.24) kPa in patients post-BD Glenn. This raised LSM was not associated with a parallel rise in liver enzymes or other laboratory markers associated with liver function. This emphasizes the suitability of FibroScan as an early and non-invasive surveillance tool for monitoring the progression of hepatic venous congestion and FALD. We have found that LSM via FibroScan can effectively be a surveillance or screening test for FALD. Serial FibroScans can be used to monitor the progress of liver disease. Raised LSM may also have a role in predicting the morbidity for completion of Fontan post-BD Glenn operation. Large-scale studies are needed to validate our findings.

Celiac Disease Affects 1% of Global Population: Who Will Manage All These Patients?

Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to the treatment with a gluten-free diet and the ensuing clinical and histological recovery. Traditionally this has been accomplished by regular on-site attendance at specialist healthcare facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited healthcare resources challenge the current centralized and non-individualized follow-up strategies. The improved non-invasive surveillance tools and online healthcare services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for.

Noninvasive Surveillance and Evolutionary Insight into Siadenovirus among Antarctic Penguins

Avian siadenoviruses infect diverse terrestrial and aquatic birds worldwide. Antarctica hosts several avian species that are susceptible to siadenovirus infection, such as penguins and South Polar skuas. However, the presence, diversity, and transmission of these viruses in Antarctic birds are poorly understood due to limited surveillance and sequence data. In this study, we performed a noninvasive surveillance of avian siadenoviruses using fecal samples collected from waterbirds at King George Island (part of South Shetland Islands, Antarctica) from late January to mid-February 2023. Polymerase chain reaction, sequencing, and phylogenetic analysis were used to investigate the occurrence, genetic diversity, and evolutionary relationships of these viruses in this unique environment. The results of these studies confirmed the presence of siadenoviruses in penguins living along the southeastern coast of King George Island. Distinct viral strains, specific to each penguin species studied, were found suggesting limited interspecies transmission and a complex viral ecosystem within Antarctic bird populations. Siadenovirus strains isolated from penguin’s species were genetically distinct from those infecting South Polar skuas. An in silico 3D modeling of hexon proteins from siadenoviruses gathered from gentoo penguins permitted to detect key amino acid substitutions in the FG2 domain that may affect capsid structure and function. The persistent prevalence of siadenoviruses in Antarctica underscores the need for ongoing surveillance to understand the evolutionary dynamics of viruses in this region. This study is the first to noninvasively detect siadenoviruses in Antarctic penguins, opening a new avenue for viral research. This approach not only sheds light on viral dynamics but also contributes to the conservation of Antarctica’s unique wildlife and biodiversity, especially in the face of increasing global warming.

Sex Differences in Cardiac Transplantation.

The goal of this review was to summarize contemporary evidence surrounding sex differences in heart transplantation (HT). Women have steadily comprised approximately 25% of waitlist candidates and HT recipients. This disparity is likely multifactorial with possible explanations including barriers in referral to advanced heart failure providers, implicit bias, and concerns surrounding sensitization. Women continue to experience higher waitlist mortality at the highest priority tiers. After HT, there are differences in post-transplant complications and outcomes. Future areas of study should include sex differences in noninvasive surveillance, renal outcomes after transplantation, and patient-reported outcomes. There are important sex-specific considerations that impact candidate selection, donor matching, waitlist and post-transplant outcomes. Concerted efforts are needed to improve referral patterns to ensure transplantation is allocated equally.

Non-invasive rejection surveillance in stable heart transplantation using local laboratory-run donor-derived cell-free DNA assay: two-centre European feasibility study

Abstract Background Monitoring adverse events is crucial after heart transplantation (HTx). Allograft rejection is a major etiological factor of graft dysfunction, hospitalisation, and death posttransplant. Endomyocardial biopsy (EMB) is the standard method of monitoring rejection; however, there are risks and limitations associated with it. The ISHLT guidelines for the care of HTx recipients have included non-invasive surveillance such as testing for donor-derived cell-free DNA (dd-cfDNA). While major studies have been conducted with patient cohorts and centralised testing in the USA, hereby we explored a European two-site cohort where dd-cfDNA was quantified at local centres by next-generation sequencing-based CE-marked assay. Purpose Our objective was to assess feasibility of assay and evaluate dd-cfDNA values in clinically stable HTx recipients. Methods HTx patients were enrolled at their scheduled visits in this cross-sectional study in 2 European HTx centres. Serial data after HTx, including clinical status, maintenance immunosuppression therapy and drug levels, diagnostic tests (blood tests, echocardiograms, coronary angiograms, EMBs), and adverse events were collected. Venous blood specimens were drawn in Streck cfDNA blood collection tubes for quantification of dd-cfDNA levels. We analysed dd-cfDNA fraction in plasma using AlloSeq cfDNA assay. For analysis, clinical stability was defined as asymptomatic patients &amp;gt;28 days post-HTx with normal graft function, without cytomegalovirus infection, history of rejection, or allograft vasculopathy. Results Between July 2021 and December 2022, 50 HTx recipients were enrolled at a median of 274 (112–395) days posttransplant. The median age at enrolment was 55.5 years. Of the total 82 dd-cfDNA results, 34 samples were excluded as they did not meet stability criteria. The median dd-cfDNA value of stable patients was 0.11% (95% CI 0.08%–0.13%). Median levels of dd-cfDNA did not differ between samples drawn in the first year after HTx (n=40) and at later time (n=8) [0.11% vs. 0.11%; p=0.41]. Of the 48 dd-cfDNA samples, 7 had values at risk based on the dd-cfDNA cut-off values from previous clinical validation trials: 4 at the injury cut-off of ≥0.20% and 3 at the severe injury threshold of ≥0.35%. Comparing clinical variables of samples with dd-cfDNA ≥0.20% (n=7) and &amp;lt;0.20% (n=41), we observed a 3-fold, non-significant increase in rate of de novo DSA formation (33.3% vs. 10.8%; p=0.19). Conclusions Our data show feasibility to analyse dd-cfDNA at the local level. In our two-site European reference cohort, dd-cfDNA is present at low levels (median 0.11%) which is within former reported ranges for clinically stable HTx recipients. Levels of dd-cfDNA do not vary beyond the first post-HTx year. The fact that in patients with de novo DSA higher dd-cfDNA levels are found; although, not statistically significant, suggests that dd-cfDNA may be a marker of subclinical rejection and requires further study.

Abstract 16189: Using Vectorcardiography to Predict Prognosis in Patients With STEMI and Heart Failure

Introduction: There is an unmet need for a non-invasive and cost-effective surveillance tool for characterizing the severity and progression of heart failure (HF) to guide evidence-based therapies. We hypothesize that changes over time in unique parameters extracted using vectorcardiography (VKG) have the potential to predict clinical outcomes in patients with HF. The pathophysiology of HF involves abnormal remodeling and a loss of cardiomyocytes, which may alter the strength and direction of the net depolarization signal. These subtle changes can be elucidated using VKG and correlated with prognosis. We hypothesize a similar approach can be utilized for patients post-STEMI as the underlying pathophysiology - loss of myocardium - is comparable and could serve as an initial proof-of-concept. Methods: We identified 209 patients discharged from Michigan Medicine between 2016 and 2021 with a diagnosis of acute STEMI. For each patient, a single 12-lead EKG pre-STEMI and &gt;1-week post-STEMI were collected. A set of 60 VKG parameters were derived by analyzing features of the QRS complex. We used LASSO regression analysis incorporating clinical variables and VKG parameters to create a predictive model for the composite outcome of mortality or HF at 90 days post-STEMI. Model accuracy was determined by randomly partitioning the data into five folds and running the logistic regression model on all folds but one. Results: Comorbid diabetes (OR = 3.04, p = 0.06), QTc post-STEMI (OR = 2.44, p &lt;0.05), and P wave onset pre-STEMI (OR = 0.41, p &lt; 0.05) were consistently predictive. A logistic regression with just these variables has a raw accuracy of 80.3% and cross-fold validation accuracy of 79.4%. Future work aims to create one of the largest pre-/post-STEMI ECG databases, with over 1,200 patients, which will be used to corroborate the above results and serve as a tool for other investigators to explore. Conclusions: ECG changes before and after a STEMI event can be used to assess the risk of mortality or HF and help guide management. The composite outcome appears to be dominated by variables that are primarily associated with arrhythmogenic death. Future work will focus on pump failure alone and determine VKG parameter predictiveness in HF specifically.

214P Development and prospective validation of a multiplex RNA urine test for noninvasive detection and surveillance of urothelial carcinoma

214P Development and prospective validation of a multiplex RNA urine test for noninvasive detection and surveillance of urothelial carcinoma