Digital Commons Network^™

Large-Scale Network Analysis Of The Cerebrospinal Fluid Proteome Identifies Molecular Signatures Of Frontotemporal Lobar Degeneration, Rowan Saloner, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic …

Screpertoire 2: Enhanced And Efficient Toolkit For Single-Cell Immune Profiling, Qile Yang, Ksenia R. Safina, Kieu Diem Quynh Nguyen, Zewen Kelvin Tuong, Nicholas Borcherding

2020-Current year OA Pubs

Single-cell adaptive immune receptor repertoire sequencing (scAIRR-seq) and single-cell RNA sequencing (scRNA-seq) provide a transformative approach to profiling immune responses at unprecedented resolution across diverse pathophysiologic contexts. This work presents scRepertoire 2, a substantial update to our R package for analyzing and visualizing single-cell immune receptor data. This new version introduces an array of features designed to enhance both the depth and breadth of immune receptor analysis, including improved workflows for clonotype tracking, repertoire diversity metrics, and novel visualization modules that facilitate longitudinal and comparative studies. Additionally, scRepertoire 2 offers seamless integration with contemporary single-cell analysis frameworks like Seurat and …

Correlation Of Ultrasound And Electrodiagnostic Evaluation In Ballistic Peripheral Nerve Injuries, Mitchell S. Mologne, Zachary D. Randall, Nathan P. Olafsen, David M. Brogan, Christopher J. Dy

2020-Current year OA Pubs

BACKGROUND: Evaluation and management of ballistic peripheral nerve injuries remain controversial, and recent series have suggested higher rates of nerve discontinuity than previously appreciated. Ultrasound (US) may aid clinicians in the management of ballistic injuries. The goal of this study was to compare US findings to electrodiagnostic and intraoperative findings to assess its accuracy in ballistic injuries.

METHODS: We conducted a retrospective review of patients with the following criteria: (1) ballistic injury to the upper or lower extremity with suspected mixed or motor peripheral nerve injury; (2) underwent electrodiagnostic studies (EDX) and peripheral nerve ultrasound. US findings were categorized as …

A Systematic Review And Meta-Analysis Of Social Cognition Among People Living With Hiv: Implications For Non-Social Cognition And Social Everyday Functioning, David E Vance, Rebecca Billings, Crystal Chapman Lambert, Pariya L Fazeli, Burel R Goodin, Mirjam-Colette Kempf, Leah H Rubin, Bulent Turan, Jenni Wise, Gerhard Hellemann, Junghee Lee

2020-Current year OA Pubs

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% …

Mollusc And Crustacean Consumption In The First 1000 Days: A Scoping Review, Brietta M Oaks, Emmanuel A Gyimah, Eliza Kleban, Kathleen Ragsdale, Lora L Iannotti

2020-Current year OA Pubs

Mollusc and crustacean consumption in the first 1000 d may improve maternal and child health by providing essential nutrients. However, in some contexts, molluscs and crustaceans have been associated with allergies and environmental contamination, potentially leading to adverse health and development outcomes. It is unclear whether the health benefits of consuming molluscs and crustaceans, collectively classified as shellfish in nutrition, are outweighed by the potential risks to pregnant women and children. We conducted a scoping review (PROSPERO: CRD42022320454) in PubMed, Scopus and EBSCO Global Health of articles published between January 2000 and March 2022 that assessed shellfish consumption during pregnancy, …

Burst Steroid Therapy And Quality Of Life In Patients With Acute Heart Failure: Insights From The Cortahf Trial, Matteo Pagnesi, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Patients hospitalized with acute heart failure (AHF) treated with a 7 day prednisone course in the CORTAHF pilot trial had a greater improvement in health-related quality of life (QoL) at Day 7 in both the overall population and in patients with baseline interleukin 6 > 13 pg/mL. This post-hoc analysis examines the specific QoL domains and the relationship between clinical signs of congestion and QoL.

METHODS: In the CORTAHF pilot trial, patients with AHF and high-sensitivity C-reactive protein (hsCRP) > 20 mg/L were randomized 1:1 to once-daily oral 40 mg prednisone for 7 days plus usual care or usual care alone. …

Chronic, Battery-Free, Fully Implantable Multimodal Spinal Cord Stimulator For Pain Modulation In Small Animal Models, Allie J Widman, Taron Bashar, Alex Burton, David Marshall Clausen, Prashant Gupta, Drew K Wolf, Jakayla Folarin-Hines, Maria Payne, John A Rogers, Kathleen W Meacham, Robert W Gereau, Philipp Gutruf

2020-Current year OA Pubs

Spinal cord stimulation (SCS) for chronic pain management is an invasive therapy involving surgical implantation of electrodes into spinal epidural space. While the clinical value and mechanistic action of the therapy is debated considerably in recent years, preclinical chronic studies employing rodent models can provide invaluable insights regarding the balance between efficacy and complications as well as mechanistic understanding of SCS therapy. However, current rodent compatible devices require tethered power delivery or bulky batteries, severely limiting the ability to probe long-term efficacy of SCS therapy. This work introduces a tether-free, small-footprint, fully implantable, battery-free SCS device compatible with rodent models, …

Masseter Muscle Size In Chronic Parotid Sialadenitis, Erika M Stephens, William E Nesmith, M Allison Ogden, Jolie L Chang

2020-Current year OA Pubs

OBJECTIVE: The relationship between masseter muscle thickness and parotid duct obstruction resulting in recurrent sialadenitis is not well defined. This study aims to evaluate masseter muscle size in patients with chronic sialadenitis of the parotid and compared to patients without parotid sialadenitis.

METHODS: Data was collected retrospectively from patients with symptomatic chronic sialadenitis of the parotid or submandibular glands. Measurements of the masseter and lateral pterygoid muscles were performed on CT or MRI imaging by two investigators who were blinded to the symptomatic gland location. Masseter thickness in the region of the parotid duct trajectory was measured.

RESULTS: Out of …

Corneal Characteristics In Children With Marfan Syndrome With Or Without Ectopia Lentis, Marisa O'Brien, Lawrence Tychsen

2020-Current year OA Pubs

IMPORTANCE: Myopia of Marfan syndrome (MFS) may be ascribed to crystalline lens subluxation, abnormal corneal curvature, and increased globe axial length. Few studies have reported these measures in MFS children who did or did not have ectopia lentis (EL).

OBJECTIVE: To measure eye findings longitudinally in MFS children with and without EL.

METHODS: A prospective, comparative case study was conducted on 24 MFS children (48 eyes). EL necessitated lensectomy and intraocular lens implantation surgery in 16/24 children (mean age 5.6 ± 2.8 years). The remaining 8/24 MFS children (mean age 11.2 ± 4.2 years) had no EL and were phakic. …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Carbapenem-Resistant Enterobacterales Peri-Rectal Colonization Prevalence On Admission To Two Intensive Care Units In An Academic Hospital In India, Armaghan-E-Rehman Mansoor, Jacaranda Van Rheenen, Ige A George, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

This study from a South Indian tertiary care hospital found a 41% peri-rectal Carbapenem-resistant

Development And Validation Of The Immune Profile Score (Ips), A Novel Multiomic Algorithmic Assay For Stratifying Outcomes In A Real-World Cohort Of Patients With Advanced Solid Cancer Treated With Immune Checkpoint Inhibitors, Alia D Zander, Douglas Adkins, Et Al.

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the oncology treatment landscape. Despite substantial improvements for some patients, the majority do not benefit from ICIs, indicating a need for predictive biomarkers to better inform treatment decisions.

METHODS: A de-identified pan-cancer cohort from the Tempus multimodal real-world database was used for the development and validation of the Immune Profile Score (IPS) algorithm leveraging Tempus xT (648 gene DNA panel) and xR (RNA sequencing) (N=1,707 development cohort; N=1,600 validation cohort). The cohort consisted of patients with advanced stage cancer with solid tumor carcinomas across 16 cancer types treated with any ICI-containing regimen as …

Music As An Implementation Strategy For Evidence-Based Health Interventions In Africa: A Systematic Review Using The Re-Aim Framework, Chidi Okafor, Shravya Allena, Olufunto A Olusanya, Temitope Ojo, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: While a growing body of scientific literature suggests that evidence-based interventions may improve health outcomes in diverse settings, little is known about the best strategies for large-scale implementation. In Africa, music-an important positive social determinant of health-leverages existing cultural values, which may effectively enhance the reach, uptake, and long-term sustainability of evidence-based interventions in the region. To understand how music interventions work, why they are effective, and with whom they resonate, this systematic review aims to evaluate the quality and empirical application of music as an implementation strategy for adopting evidence-based interventions in Africa using the RE-AIM framework as …

Mechanisms Of Change Of A Multifaceted Implementation Strategy On Fidelity To A Guideline For The Prevention Of Mental Health Problems At The Workplace: A Mechanism Analysis Within A Cluster-Randomized Controlled Trial, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak

2020-Current year OA Pubs

BACKGROUND: Occupational guidelines exist to support workplaces with the prevention of mental health problems (MHP) among their staff. However, knowledge of effective implementation strategies to support their implementation is limited. This study experimentally tested whether a multifaceted implementation strategy - comprising an educational meeting, five workshops, implementation teams, small cyclical tests of change, and facilitation - improves fidelity to a guideline for preventing MHP in a school setting through the pathway of change of the Capability Opportunity Motivation-Behavior (COM-B)-model. To gain a more granular understanding of the mechanisms of change, the Theoretical Domains Framework (TDF) was used to specify mediators …

Preterm Birth Increases Susceptibility To Hyperglycemia Induced Glomerular Alterations In Male Mice, Aleksandra Cwiek, Kevin M Bennett, Edwin J Baldelomar, Et Al.

2020-Current year OA Pubs

Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project was to determine the effect of preterm birth on kidney health after exposure to hyperglycemia. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, …

Allele-Specific Vitamin D Receptor Binding Is Associated With Pediatric-Onset Multiple Sclerosis, Defne Yilmaz, Soe Mar, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels and genetic variation related to vitamin D receptor (VDR) binding. The objective was to identify whether VDR binding variants (VDR-BVs) previously implicated in adult-onset MS were associated with pedMS using genetic instrumental variables (GIVs).

METHODS: Using previously identified VDR-BVs to construct individual GIVs with two-sample MR, we investigated associations with pedMS in …

Mechanisms Of Photoreceptor Protection Upon Targeting The Nrl-Nr2e3 Pathway, Daniel P Murphy, Alexander V Kolesnikov, Cynthia L Montana, Zaid M Khaja, Yu Liu, Vladimir J Kefalov, Joseph C Corbo

2020-Current year OA Pubs

Acute knockout of the rod photoreceptor transcription factor

Methods For Joint Modeling Of Longitudinal Omics Data And Time-To-Event Outcomes: Applications To Lysophosphatidylcholines In Connection To Aging And Mortality In The Long Life Family Study, Konstantin G Arbeev, Olivia Bagley, Svetlana V Ukraintseva, Alexander Kulminski, Eric Stallard, Michaela Schwaiger-Haber, Gary J Patti, Yian Gu, Anatoliy I Yashin, Michael A Province

2020-Current year OA Pubs

Studying the relationships between longitudinal changes in omics variables and event risks requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process models [SPM]) to longitudinal metabolomics data from the Long Life Family Study, focusing on the understudied associations of longitudinal changes in lysophosphatidylcholines (LPCs) with mortality and aging-related outcomes. We analyzed 23 LPC species, with 5,066 measurements of each in 3,462 participants, 1,245 of whom died during follow-up. JM analyses found that higher levels of the majority of LPC species were associated with lower mortality risks, with the …

Candidate Interventions For Integrating Hypertension And Cardiovascular-Kidney-Metabolic Care In Primary Health Settings: Hearts 2.0 Phase 1, Andres Rosende, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: HEARTS in the Americas is the regional adaptation of the WHO Global HEARTS Initiative, aimed at helping countries enhance hypertension and cardiovascular disease (CVD) risk management in primary care settings. Its core implementation tool, the HEARTS Clinical Pathway, has been adopted by 28 countries. To improve the care of hypertension, diabetes, and chronic kidney disease (CKD), HEARTS 2.0 was developed as a three-phase process to integrate evidence-based interventions into a unified care pathway, ensuring consistency across fragmented guidelines. This paper focuses on Phase 1, highlighting targeted interventions to improve and update the HEARTS Clinical Pathway.

METHODS: First, the coordinating …

Cytogenetic Annotation Automation In Myelodysplastic Syndrome Research Databases, Samuel Urrutia, Kelly S Chien, Ziyi Li, Alexandre Bazinet, Guilin Tang, Guillermo Garcia-Manero

2020-Current year OA Pubs

No abstract provided.

Dna Repair And The Contribution To Chemotherapy Resistance, Ksenija Nesic, Phoebe Parker, Elizabeth M Swisher, John J Krais

2020-Current year OA Pubs

The DNA damage response comprises a set of imperfect pathways that maintain cell survival following exposure to DNA damaging agents. Cancers frequently exhibit DNA repair pathway alterations that contribute to their intrinsic genome instability. This, in part, facilitates a therapeutic window for many chemotherapeutic agents whose mechanisms of action often converge at the generation of a double-strand DNA break. The development of therapy resistance occurs through countless molecular mechanisms that promote tolerance to DNA damage, often by preventing break formation or increasing repair capacity. This review broadly discusses the DNA damaging mechanisms of action for different classes of chemotherapeutics, how …

Active Transport Enables Protein Condensation In Cells, Gaurav Chauhan, Edward G Wilkinson, Yaning Yuan, Samuel R Cohen, Masayuki Onishi, Rohit V Pappu, Lucia C Strader

2020-Current year OA Pubs

Multiple factors drive biomolecular condensate formation. In plants, condensation of the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 attenuates response to the plant hormone auxin. Here, we report that actin-mediated movement of cytoplasmic ARF condensates enhances condensation. Coarse-grained molecular simulations of active polymers reveal that applied forces drive the associations of macromolecules to enhance phase separation while giving rise to dense phases that preferentially accumulate motile molecules. Our study highlights how molecular motility can drive phase separation, with implications for motile condensates while offering insights into cellular mechanisms that can regulate condensate dynamics.

Diverse Cell Types Establish A Pathogenic Immune Environment In Peripheral Neuropathy, Julie Choi, Amy Strickland, Hui Qi Loo, Wendy Dong, Lilianne Barbar, A Joseph Bloom, Yo Sasaki, Sheng Chih Jin, Aaron Diantonio, Jeffrey Milbrandt

2020-Current year OA Pubs

Neuroinflammation plays a complex and context-dependent role in many neurodegenerative diseases. We identified a key pathogenic function of macrophages in a mouse model of a rare human congenital neuropathy in which SARM1, the central executioner of axon degeneration, is activated by hypomorphic mutations in the axon survival factor NMNAT2. Macrophage depletion blocked and reversed neuropathic phenotypes in this sarmopathy model, revealing SARM1-dependent neuroimmune mechanisms as key drivers of disease pathogenesis. In this study, we investigated the impact of chronic subacute SARM1 activation on the peripheral nerve milieu using single cell/nucleus RNA-sequencing (sc/snRNA-seq). Our analyses reveal an expansion of immune cells …

Subcortical Correlates Of Consciousness With Human Single Neuron Recordings, Michael Pereira, Nathan Faivre, Fosco Bernasconi, Nicholas Brandmeir, Jacob E Suffridge, Kaylee Tran, Shuo Wang, Victor Finomore, Peter Konrad, Ali Rezai, Olaf Blanke

2020-Current year OA Pubs

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness remains unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing …

A Cross-Sectional Study Of The Role Of Epithelial Cell Injury In Kidney Transplant Outcomes, Philip F. Halloran, Tarek Alhamad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

METHODS: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

RESULTS: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. …

Treatment Of Overactive Katp Channels With Glibenclamide In A Zebrafish Model And A Clinical Trial In Humans With Cantú Syndrome, Lotte Kleinendorst, Sarah E Siegelaar, Helen I Roessler, Lema Meiwand, Malou Van Den Boogaard, Rianne H A C M De Bruin-Bon, Kirsten F Van Duinen, R Nils Planken, Elisabeth H Jaspars, Patrick M J H Kemperman, Berto J Bouma, Colin G Nichols, Marcel W Bekkenk, Gijs W Van Haaften, Mieke M Van Haelst

2020-Current year OA Pubs

This study explores the efficacy of glibenclamide, a K

Patient-Reported Social Determinants Of Health In Patients With Heart Failure, Kenneth E Freedland, Brian C Steinmeyer, Judith A Skala, Robert M Carney, Michael W Rich

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDOH) complicate medical care and affect clinical outcomes, but the lack of a reliable structured interview for medical patients has impeded clinical assessment and research on SDOH. We assessed the reliability and validity of a newly developed SDOH Patient Interview Form and investigated SDOH in patients with heart failure.

METHODS: The SDOH Patient Interview Form was administered to recently hospitalized patients with heart failure between January 2021 and April 2024. The interviews were recorded, and 50 were randomly selected for the interrater reliability analysis.

RESULTS: The sample included 367 participants (mean age, 61.2±12.1 years; 42.5% …

Sksr1 Identified As Key Virulence Factor In Cryptosporidium By Genetic Crossing, Wei He, Lianbei Sun, Tianyi Hou, Zuwei Yang, Fuxian Yang, Shengchen Zhang, Tianpeng Wang, Xinran Wang, Na Li, Yaqiong Guo, L David Sibley, Yaoyu Feng, Lihua Xiao

2020-Current year OA Pubs

Cryptosporidium is a major cause of severe diarrhea. Although Cryptosporidium isolates exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we use classical genetics to cross two Cryptosporidium parvum isolates of different virulence and use bulk segregant analysis of whole-genome sequences from the progeny to identify quantitative trait loci (QTL) associated with Cryptosporidium infectivity and virulence. Of the 23 genes in three QTL, two have loss-of-function mutations in the low-virulence isolates, including the SKSR1 gene encoding a variant secretory protein. Deletion of the SKSR1 gene or expression of the frame-shifted …

Rapamycin Treatment For Alzheimer's Disease And Related Dementias: A Pilot Phase 1 Clinical Trial, Mitzi M Gonzales, Miranda E Orr, Yingxin He, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rapamycin has been shown to extend lifespan and acts on pathologies underlying Alzheimer's disease and related dementias in animal models. However, rapamycin's clinical application remains underexplored.

METHODS: We conducted a single-site open-label phase 1 clinical trial (ClinicalTrials.gov: NCT04200911) to examine the effects of rapamycin in humans. Eligible participants were people 55-85 years old with mild cognitive impairment or early-stage dementia, which was defined as having a Global Clinical Dementia Rating Scale Score of 0.5-1. All participants received rapamycin (1 mg/day) for eight weeks. The primary aim was to evaluate rapamycin's central nervous system penetrance by assaying drug levels in …

Rationale And Design Of The Repeat Trial: A Multicenter Randomized Trial Comparing Redo Surgical Aortic Valve Replacement To Valve-In-Valve Transcatheter Aortic Valve Replacement, Matthias Raschpichler, Suzanne De Waha, Stefan Blankenberg, Marcio A Diniz, Emilia Bagiella, Annetine C Gelijns, Vinicius F Calsavara, Aakriti Gupta, Niklas Schofer, Tsuyoshi Kaneko, Mohamed Abdel-Wahab, Holger Thiele, Raj Makkar, Michael A Borger

2020-Current year OA Pubs

BACKGROUND: Redo surgical aortic valve replacement (rSAVR) has for long been the therapeutic reference standard for degenerated surgical aortic bioprostheses. Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as an alternative for patients at high surgical risk due to its lower invasiveness. The long-term clinical efficacy of ViV-TAVR in patients at low to intermediate surgical risk remains unknown.

METHODS AND RESULTS: To compare clinical outcomes of redo surgical aortic valve replacement versus ViV-TAVR in low- to intermediate-risk patients with degenerated surgical aortic bioprostheses. REPEAT (Repeat Intervention for Deteriorated Surgical Bioprosthetic Aortic Valves) is an investigator-initiated, international, multicenter, randomized, parallel, open-label …