Digital Commons Network^™

Cognitive Reserve Predicts Baseline Tau Burden In The Us Pointer Trial Imaging Cohort, Valory N Pavlik, Chris J Weber, Joseph C Masdeu, Laura D Baker, Melissa M Yu, Michele York, Rachel A Whitmer, Susan M Landau, Theresa M Harrison, Tomas M Holland, Laura Lovato

Faculty, Staff and Students Publications

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

A Computer Vision And Machine Learning Approach To Classify Views In Distal Radius Radiographs, Rohan Vemu, Dion Birhiray, Bassem Darwish, Raven Hollis, Sai Unnam, Srikhar Chilukuri, Lorenzo Deveza

Faculty, Staff and Students Publications

Advances in computer vision and machine learning have augmented the ability to analyze orthopedic radiographs. A critical but underexplored component of this process is the accurate classification of radiographic views and localization of relevant anatomical regions, both of which can impact the performance of downstream diagnostic models. This study presents a deep learning object detection model and mobile application designed to classify distal radius radiographs into standard views-anterior-posterior (AP), lateral (LAT), and oblique (OB)- while localizing the anatomical region most relevant to distal radius fractures. A total of 1593 deidentified radiographs were collected from a single institution between 2021 and …

Predictors Of Decannulation Success In Tracheostomy: A 10-Year Analysis Of The Global Tracheostomy Collaborative Database, Charissa J Zaga, Carly E Milliren, Brendan A Mcgrath, Christina J Yang, Bradley A Schiff, Stephen J Warrillow, Jennifer K Henningfeld, Prudence A Gregson, Joshua R Bedwell, Karen M Beaudet, Michael J Brenner, Vinciya Pandian

Faculty, Staff and Students Publications

Objective: Decannulation is a critical milestone in functional recovery after tracheostomy, but standardized guidelines are lacking. This study examined factors associated with tracheostomy decannulation success, comparing hospital utilization, adverse events, and survival outcomes between decannulated and non-decannulated patients.

Study design: Retrospective, observational study.

Setting: Data were collected from 25 hospitals participating in the Global Tracheostomy Collaborative (GTC) in the United States, Australia, and the United Kingdom.

Methods: Prospectively collected data from adult patients who underwent tracheostomy from 2013 to 2022 were analyzed. Outcomes included decannulation success, hospital utilization metrics (intensive care unit [ICU] admissions, mechanical ventilation use, tracheostomy duration, and …

Targeting Rbm10-Repressed Rorb Activity In Liquid Condensates Inhibits Lysosomal Biogenesis And Neuroblastoma Progression Via Affecting Nf-Κb Signaling, Yanhua Guo, Xiaojing Wang, Chunhui Yang, Zhijie Wang, Xiaolin Wang, Xinyue Li, Jiaying Qu, Shunchen Zhou, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

Neuroblastoma (NB), a pediatric solid malignancy, is distinguished by hetergenous clinical characteristics, including tumor aggressiveness or spontaneous regression. Nevertheless, the regulatory mechanisms and therapeutic approaches underlying these processes are still mainly unknown. Herein, RAR-related orphan receptor B (RORB) as a transcription factor repressing nuclear factor kappa B (NF-κB) signaling involved in lysosomal biogenesis of NB. RORB attenuated the growth, invasiveness, and metastatic spread of NB cells are identified. From a mechanistic perspective, RORB increased the transcription of nuclear receptor subfamily 1 group D member 1 (NR1D1)- or RIO kinase 3 (RIOK3)- in a circadian clock-dependent manner, resulting in suppression of …

Correction: Significant Increase Of Firework Induced Eye Injuries In Germany And The Netherlands- Are We Doing Enough To Protect Minors And Bystanders?, Ameli Gabel-Pfisterer, Stefan Johann Lang, Daniel Boehringer, Hansjürgen Agostini, Lotte C De Geus, Jan Tjeerd De Faber

Faculty, Staff and Students Publications

No abstract provided.

Consequences Of Adverse Events In Cancer Immunotherapy Combinations - A Comprehensive Real-World Analysis, Siv Gyda Aanes, Carsten Nieder, David Westfall Bates, Siri Wiig, Ellinor Christin Haukland

Faculty, Staff and Students Publications

Background: Immune checkpoint inhibitors (ICIs) are pivotal in systemic anticancer therapy. The aim of the study was to investigate incidence, severity and consequences of immune-related adverse events (irAEs) in ICI combinations by comparing different adverse events classification systems.

Methods: A retrospective multicentre cohort study included patients treated with ICI combinations. IrAEs were assessed by CTCAE v.5, NCC MERP index and SITC consensus for chronic irAEs.

Results: Among 612 patients, 244 (40%) experienced 354 irAEs, in total 58 irAEs per 100 patients varying between treatments. Higher incidence was observed for autoimmune disease, thoracic radiotherapy, melanoma, dual ICI and ICI/TKI. Severe irAEs …

Frailty And Nutritional Status Predict Postoperative Complications In Radical Cystectomy Patients, David E Hinojosa-Gonzalez, Gal Saffati, Gustavo Salgado-Garza, Cecilio Armengol-García, Bailey Slawin, Sienna Blackwell, Jennifer M Taylor, Jeremy R Slawin

Faculty, Staff and Students Publications

Introduction: Radical cystectomy (RC) is associated with significant morbidity and mortality. While frailty and nutritional status have emerged as important predictors of surgical outcomes, their impact on RC complications remains incompletely characterized. We aimed to evaluate the relationship between frailty (using the Modified Frailty Index-5 [mFI-5], nutritional status (using the Nutritional Risk Index [NRI]), and postoperative outcomes in patients undergoing RC.

Methods: We conducted a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Frailty was defined as mFI-5 score ≥2 and malnutrition as NRI ≤97.5. Hypoalbuminemia was defined as preoperative albumin ≤3.5. Outcomes included …

Coco-St Detects Global And Local Biological Structures In Spatial Transcriptomics Datasets, Muhammad Aminu, Bo Zhu, Natalie Vokes, Hong Chen, Lingzhi Hong, Jianrong Li, Junya Fujimoto, Mehdi Chaib, Yuqiu Yang, Bo Wang, Alissa Poteete, Monique B Nilsson, Xiuning Le, Tina Cascone, David Jaffray, Nicholas Navin, Tao Wang, Lauren A Byers, Don L Gibbons, John Heymach, Ken Chen, Chao Cheng, Jianjun Zhang, Jia Wu

Faculty, Staff and Students Publications

Spatial domain detection methods often focus on high-variance structures, such as tumour-adjacent regions with sharp gene expression changes, while missing low-variance structures with subtle gene expression shifts, like those between adjacent normal and early adenoma regions. Here, to address this, we introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive feature representation framework. By comparing a target sample with a background sample, CoCo-ST detects both high-variance, broadly shared structures and low-variance, tissue-specific features. It offers technical advantages, including multisample integration, batch-effect correction and scalability across technologies from spot-level Visium data to single-cell Xenium Prime 5K and subcellular Visium HD …

Perfluoroalkyl Substance Pollutants Disrupt Microglia Function And Trigger Transcriptional And Epigenomic Changes, Yating Cheng, Jian-Rong Li, Hangjin Yu, Shuang Li, Boranai Tychhon, Chao Cheng, Yi-Lan Weng

Faculty, Staff and Students Publications

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired …

The Ifit2-Ifit3 Antiviral Complex Targets Short 5′ Untranslated Regions On Viral Mrnas For Translation Inhibition, Dustin R Glasner, Candace Todd, Brian Cook, Agustina D'Urso, Shivani Khosla, Elena Estrada, Jaxon D Wagner, Mason D Bartels, Chuan-Tien Hung, Pierce Ford, Jordan Prych, Kathryn S Hatch, Brian A Yee, Kaori M Ego, Qishan Liang, Sarah R Holland, James Brett Case, Kevin D Corbett, Michael S Diamond, Benhur Lee, Gene W Yeo, Mark A Herzik, Eric L Van Nostrand, Matthew D Daugherty

Faculty, Staff and Students Publications

Recognition of foreign RNA is critical for the innate immune response to viruses. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFIT) 2 and 3 are highly upregulated following viral infection, but mechanistic insight into their antiviral role is lacking. Here we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can serve as a molecular pattern for innate immune recognition via IFIT2 and IFIT3. Structure determination of the IFIT2-IFIT3 complex at 3.2 Å using cryo-EM reveals a domain-swapped heterodimer that is required for recognition of the viral mRNA 5' end, translation inhibition and antiviral activity. Critically, viral …

Paediatric Difficult Intubations And The Impact Of Timing Of Weekend Versus Weekday Cases: An Analysis Of The Pediatric Difficult Intubation Registry, Christy J Crockett, Judit Szolnoki, Sabina Khan, Angela C Lee, Alexander Kaizer, Patrick Olomu, Melissa Brooks Peterson

Faculty, Staff and Students Publications

Background: Off-hours presentation has been shown to be independently associated with tracheal intubation-related adverse events in patients with predicted difficult airway. The comparison of the complication rates of paediatric difficult intubations on weekends vs weekdays is unknown. The primary objective of this retrospective review is to determine the complication rates for paediatric difficult intubation cases that occur on a weekend vs a weekday.

Methods: We performed a retrospective review of data from the Pediatric Difficult Intubation registry, with service dates June 8, 2012 to May 9, 2023, to compare complication rates (total complications, hypoxaemia, non-hypoxaemia complications, and first-attempt success rate) …

Pediatric Heart-Kidney Transplantation, Swati Choudhry, Kriti Puri, Vikas R Dharnidharka

Faculty, Staff and Students Publications

Heart transplantation is regarded as the definitive treatment for advanced pediatric heart failure. However, concomitant kidney dysfunction often complicates candidate selection for isolated heart transplantation. Prolonged venous congestion, nephrotoxic exposures, and recurrent episodes of acute kidney injury can result in varying degrees of renal impairment. Differentiating between reversible kidney injury secondary to cardiorenal syndrome and irreversible intrinsic renal disease remains a major challenge. Pediatric heart-kidney transplantation has shown survival benefits for patients with end-stage heart failure requiring chronic dialysis, yet its role in patients with less severe renal dysfunction is less clearly defined. This review summarizes the current evidence on …

Selective Agonism Of Liver And Gut Fxr Prevents Cholestasis And Intestinal Atrophy In Parenterally Fed Neonatal Pigs, Yanjun Jiang, Zhengfeng Fang, Gregory Guthrie, Barbara Stoll, Shaji Chacko, Sen Lin, Bolette Hartmann, Jens J Holst, Harry Dawson, Jose J Pastor, Ignacio R Ipharraguerre, Douglas G Burrin

Faculty, Staff and Students Publications

We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs. Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA) or increasing doses of obeticholic acid (OCA) for 19 days. Enteral OCA (5 and 15 mg/kg), but not CDCA (30 mg/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA, and OCA, and their relative proportions were increased by the type of bile acid (CDCA …

Factors Influencing 25-Year Survival In Pediatric Liver Transplant Recipients, Garrett Wortham, Megan Crawford, John Miggins, Chun-Sing Huang, John A Goss, Abbas Rana, Nhu Thao Galván

Faculty, Staff and Students Publications

Background: This study assesses the impact of cholestatic liver disease, including biliary atresia, on 25-year survival post-transplantation and additional factors influencing long-term outcomes after pediatric liver transplantation.

Methods: We conducted a retrospective analysis of pediatric liver transplant recipients (1987-1998) using de-identified data from the OPTN 2023 Liver Database. After exclusions for multi-organ transplants (n = 222), prior transplants (n = 2256), and deaths within 1 year (n = 526), 2429 patients remained, including 645 with cholestatic disease. Univariate and multivariate analyses identified factors associated with 25-year survival.

Results: A primary diagnosis of cholestatic disease was associated with improved 25-year survival …

From Pachymeningitis Hemorrhagica To Abusive Head Trauma: A Journey Through The Centuries, Oliver Berthold, Flora Blangis, Christopher Spencer Greeley

Faculty, Staff and Students Publications

The development of medical knowledge follows specific principles. These also apply to abusive head trauma. The seminal literature from the early 20th century is based on earlier research from Europe, which is fundamental to understand the evolution of understanding and nomenclature of abusive head trauma. A review of original medical literature on intracranial injuries in children, published in German, English, and French, was conducted using PubMed and Google Scholar for articles before 1950. The primary search focused on subdural hemorrhages and pachymeningitis in children, followed by a snowball search of references. Full texts of available manuscripts were reviewed. Primary literature …

Differences In Patient And Parent Preferences For Prognostic Communication Across Disease Milestones In Advanced Childhood Cancer, Rachel A Kentor, Shoshana Mehler, Caroline Christianson, Harmony Farner, Tara M Brinkman, Justin N Baker, Pamela S Hinds, Jennifer W Mack, Erica C Kaye

Faculty, Staff and Students Publications

Background: Navigating prognostic communication is challenging for clinicians caring for adolescents and young adults (AYAs) with poor-prognosis cancer. Presently, little is known about how AYA and parent preferences for prognostic disclosure evolve over time. This study explored communication preferences at key illness milestones of disease progression to inform individualized, person-centered approaches to optimize prognostic disclosure.

Procedure: Sixty-five participants, including 25 AYAs aged 12-25 years and 40 parents, were recruited at distinct illness timepoints-diagnosis, relapse/progression, Phase I/II trial enrollment, and bereavement-to participate in semi-structured interviews about their preferences for timing, style, and content of prognostic communication. Rapid analysis was conducted to …

Beyond Seizures As An Outcome Measure: A Global Severity Scoring System For Cdkl5 Deficiency Disorder, Peter Jacoby, Eric D Marsh, Scott Demarest, Jacinta M Saldaris, Helen Leonard, Heather E Olson, Joni N Saby, Elia Pestana-Knight, Rajsekar Rajaraman, Dana Price, Judith Weisenberg, Bernhard Suter, Jenny Downs, Tim A Benke

Faculty, Staff and Students Publications

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance …

Gregor: Accelerating Genomics For Rare Diseases, Moez Dawood, Ben Heavner, Marsha M Wheeler, Rachel A Ungar, Jonathan Lotempio, Laurens Wiel, Seth Berger, Jonathan A Bernstein, Jessica X Chong, Emmanuèle C Délot, Evan E Eichler, James R Lupski, Ali Shojaie, Michael E Talkowski, Alex H Wagner, Chia-Lin Wei, Christopher Wellington, Matthew T Wheeler, Gregor Partner Members, Claudia M B Carvalho, Richard A Gibbs, Casey A Gifford, Susanne May, Danny E Miller, Heidi L Rehm, Kaitlin E Samocha, Fritz J Sedlazeck, Eric Vilain, Anne O'Donnell-Luria, Jennifer E Posey, Lisa H Chadwick, Michael J Bamshad, Stephen B Montgomery, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium

Faculty, Staff and Students Publications

Rare diseases are collectively common, affecting approximately 1 in 20 individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in next-generation sequencing, development of new computational and functional genomics approaches to prioritize genes and variants and increased global sharing of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize and evaluate emerging genomics technologies …

Neurodevelopmental Abnormalities Underlying Behavioral Deficits In A Model Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Michael R Williamson, Vaishnav Krishnan, Mahyar J Hedayatpour, Adam C Adler, Nandani Adyapak, Chris S Ward, Russell Ray, David Durgan, Farrah Kheradmand, Benjamin Deneen

Faculty, Staff and Students Publications

Rationale: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

Objectives: To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

Methods: We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the …

Point/Counterpoint: Upfront Braf Inhibition For Adult Braf-Mutant High-Grade Gliomas, Sebastien Perreault, Marjolein Geurts, Jasia Mahdi, Karisa C Schreck, Matthias Preusser, Patrick Y Wen, Mary Jane Lim-Fat, Jan-Michael Werner

Faculty, Staff and Students Publications

No abstract provided.

Sim And Learn: Simulation And Its Value In Neurology Education, Laveena Singla, Fariha Jamal, Anju Abu, Dana Ionel, Amtul Farheen

Faculty, Staff and Students Publications

Background: Simulation is a widely used health care education tool. Its use is increasing in acute neurologic conditions and has great potential to help trainees better perform procedures and enhance communication and professionalism.

Observations: This article describes the different neurologic simulations used as educational tools and the evidence that demonstrates their value. It also details the benefits afforded by simulations (eg, improved adherence to protocols, reduced door-to-needle time in stroke care) and areas of opportunity. It includes the use of virtual reality to allow trainees to interact with 3-dimensional models of the brain as well as augmented reality to view …

Myeloid-Specific Camkk2 Deficiency Protects Against Diet-Induced Obesity And Insulin Resistance By Rewiring Metabolic Gene Expression And Enhancing Energy Expenditure, Andrea R Ortiz, Kevin Nay, Brittany A Stork, Adam M Dean, Sean M Hartig, Cristian Coarfa, Surafel Tegegne, Christopher Rm Asquith, Daniel E Frigo, Brian York, Anthony R Means, Mark A Febbraio, John W Scott

Faculty, Staff and Students Publications

Objective: Obesity is associated with chronic, low-grade inflammation in metabolic tissues such as liver, adipose tissue and skeletal muscle implicating insulin resistance and type 2 diabetes as inflammatory diseases. This inflammatory response involves the accumulation of pro-inflammatory macrophages in these metabolically relevant organs. The Ca2+-calmodulin-dependent protein kinase kinase-2 (CAMKK2) is a key regulator of cellular and systemic energy metabolism, and a coordinator of macrophage-mediated inflammatory responses. However, its role in obesity-associated metabolic dysfunction is not fully defined. The aim of this study was to determine the contribution of CAMKK2 to the regulation of inflammation and systemic metabolism during diet-induced obesity. …

Indomethacin-Induced Ductus Arteriosus Closure And Aortopulmonary Collateral Formation In Fetal Ebstein Anomaly With Circular Shunt, Mounica Y Rao, Ruth M Vaughan, Shaine A Morris, Nancy A Ayres, Maggie J Nguyen, Jianhong Zhang, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

• Indomethacin may improve hemodynamics in fetal Ebstein anomaly with circular shunt. • Ductal closure with indomethacin can impair pulmonary blood flow and growth. • Ductal closure may result in subsequent development of APCs. • Irreversible ductal closure may affect postnatal surgical palliation. • Fetal echocardiography is vital for early intervention and medication titration.

Pharmacological Treatment For Patients With Obesity And Heart Failure: Focus On Glucagon-Like Peptide-1 Receptor Agonists. European Journal Of Heart Failure Expert Consensus Document, Luca Monzo, Gianluigi Savarese, Wilfried Mullens, Amr Abdin, Biykem Bozkurt, Ovidiu Chioncel, Seif El Hadidi, Thomas M Gorter, Riccardo M Inciardi, Mark C Petrie, Gabriele G Schiattarella, Davide Stolfo, Marco Metra, Nicolas Girerd

Faculty, Staff and Students Publications

There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP-1 RAs and GIP/GLP-1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body …

Urinary Markers In Heart Failure – Types, Timing And Thresholds. European Journal Of Heart Failure Expert Consensus Document, Masatake Kobayashi, Biykem Bozkurt, Peder Langeland Myhre, Juan Carlos Lopez Azor, Mateusz Guzik, Gracjan Iwanek, Guillaume Baudry, Marta Cobo-Marcos, Òscar Miró, Jeroen Dauw, Piotr Ponikowski, Wilfried Mullens, Alberto Palazzuoli, Marco Metra, Jan Biegus

Faculty, Staff and Students Publications

Several urinary markers reflect disease severity and have the potential to support the management of heart failure (HF). Collecting urine samples is easy and inexpensive, and urine sample composition can be altered not only by underlying kidney impairments (i.e. filtration barrier damage and tubular injury) but also via neurohormonal and inflammatory activation, ageing, comorbidities, other medical conditions and pharmacological interventions. For instance, urinary sodium may help to predict the response to loop diuretic therapy in acute HF, while albuminuria is used as a risk marker and therapeutic target for the progression of cardiovascular and kidney diseases in chronic HF, especially …

Management Of Patients With Heart Failure At High Risk Of Hyperkalaemia: The Care-Hk In Hf Registry, Stephen J Greene, Andrew J Sauer, Michael Böhm, Biykem Bozkurt, Javed Butler, John G F Cleland, Andrew J S Coats, Nihar R Desai, Diederick E Grobbee, Ellie Kelepouris, Fausto Pinto, Giuseppe Rosano, Victoria Donachie, Solenn Fabien, Sandra Waechter, Maria G Crespo-Leiro, Martin Hülsmann, Tibor Kempf, Otmar Pfister, Anne-Catherine Pouleur, Manish Saxena, Martin Schulz, Maurizio Volterrani, Stefan D Anker, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Aims: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia.

Methods and results: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, …

Albuminuria As A Diagnostic Criterion And A Therapeutic Target In Heart Failure And Other Cardiovascular Disease, Biykem Bozkurt, Patrick Rossignol, Joseph A Vassalotti

Faculty, Staff and Students Publications

The high disease burden and bidirectional relationship of chronic kidney disease (CKD), heart failure (HF) and other cardiovascular disease (CVD) necessitate the need for early diagnosis of these diseases. While current screening and detection methods are recommended by CKD and CVD guidelines, their adoption in practice is low. Urine albumin-to-creatinine ratio (uACR) is recognized as a diagnostic marker for CKD and a prognostic marker for CKD progression, HF and CVD outcomes, therefore albuminuria changes have been accepted as a surrogate outcome for kidney and cardiovascular endpoints. Furthermore, clinical trials investigating guideline-directed medical therapies have shown that uACR reductions are accompanied …

Multiomic And Electrophysiologic Analyses Reveal That An Inherited Mrc2 Variant Causes Fibroblast Dysfunction And Increased Atrial Fibrillation Susceptibility, Kevin S Ho, Joshua A Keefe, Shuai Zhao, Mohit M Hulsurkar, Sung Yun Jung, Md Abul Hassan Samee, Xander H T Wehrens

Faculty, Staff and Students Publications

A recent study identified a rare variant in the mannose receptor C type 2 (MRC2) gene in individuals with familial reentrant supraventricular tachycardia, a Wolff-Parkinson-White (WPW) electrocardiogram pattern, and structurally normal hearts. WPW syndrome is associated with atrial fibrillation (AF), and MRC2 was recently proposed as a protective gene for AF. We determined whether the E990G-heterozygous (het) loss-of-function variant in Mrc2 increases AF susceptibility and identified aberrant cellular mechanisms resulting from Mrc2 deficiency in atrial cardiofibroblasts (ACFs) and atrial tissue in mice that may promote AF. Programmed electrical stimulation was performed to determine AF susceptibility in Mrc2 E990G-het …

Concerns Regarding The Standard Deviation Of Individual Responses For Assessing Treatment Response Heterogeneity, Aaron R Caldwell, David B Allison, Andrew W Brown, Gary L Gadbury, Thirupathi Reddy Mokalla, R Drew Sayer, Andrew D Vigotsky

Children’s Nutrition Research Center Staff Publications

The estimation of treatment response heterogeneity (TRH) is increasingly important as medicine moves toward personalized approaches. While various statistical methods have been proposed to quantify TRH in parallel-group trials, the standard deviation of individual responses (SDIR) has gained prominence within physiological research. This method is intended to quantify individual response variation by comparing standard deviations of change scores between intervention and control groups. We acknowledge that SDIR represents an improvement over many other flawed approaches that often involve responder counting. However, SDIR has critical limitations: 1) it cannot overcome the fundamental problem of causal inference because the correlation between potential …