Circulatory and Respiratory Physiology Commons^™

E3 Ligase Rnf145 Regulates Airway Smooth Muscle Cell Proliferation Via The Pp2a-P70s6k Signaling Axis, Vijaya Kumar Gangipangi, Erin O. Curley, Deepak A. Deshpande, Pawan Sharma

Center for Translational Medicine Faculty Papers

Airway smooth muscle (ASM) is a key determinant of airway caliber and a major contributor to structural remodeling in obstructive lung diseases, including asthma and COPD. ASM proliferation is regulated by transcriptional and post-transcriptional mechanisms, including ubiquitin-dependent protein turnover mediated by E3 ubiquitin ligases. Here, we investigated the role of the RING-type E3 ligase RNF145 in mitogenic signaling and ASM cell proliferation. Human ASM cells were transfected with RNF145 shRNA or treated with the E3 ligase inhibitor SMER3, followed by stimulation with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF). RNF145 knockdown or SMER3 treatment dose-dependently inhibited mitogen-induced ASM …

Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”¹ Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.

METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: The prognostic value of baseline Quantitative Flow Ratio (QFR) in real-world patients remains unclear. This study aimed to evaluate the prognostic value of baseline QFR and its three-tier model-low, grey-zone, and high QFR-in patients with single-vessel intermediate stenosis.

METHODS: This retrospective study included 478 patients with QFR between 0.70 and 0.90 who underwent coronary angiography between May and June 2023. Patients were stratified into Low (0.70-0.74), Grey-Zone (0.75-0.85), and High (0.86-0.90) QFR groups. The primary endpoint was major adverse cardiac events (MACE); the key secondary endpoint was target vessel failure (TVF). Kaplan-Meier and Cox proportional hazards models …

Short Term Hemodynamic Effects Of Atrial Fibrillation In A Closed-Loop Human Cardiac-Baroreflex System, Oluwasanmi Adeodu, Michelle Gee, Babak Mahmoudi, Rajanikanth Vadigepalli, Mayuresh V. Kothare

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Atrial fibrillation (AF) remains the leading cardiac cause of stroke and AF-related death rate in the United States has been increasing for over twenty years. While the effect of standalone AF on heart rate is well established, there is a lack of clarity on its impact on other critical hemodynamic metrics. This is ostensibly due to interaction with other common comorbidities, especially hypertension. In addition, AF has a complex relationship with the state of the baroreflex. Evidence indicates that baroreflex sensitivity (BRS), the ability of the intrinsic cardiac control system to initiate parasympathetic response, is suppressed during AF. Therefore, a …

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And Adverse Clinical Outcomes In Patients With Pulmonary Hypertension And Chronic Kidney Disease, Andrew Geller, Jose Manuel Martinez Manzano, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Simone Jarrett, Kevin Bryan Lo, Christian Witzke

Einstein Health Papers

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between …

Trajectory Of Iron And Red Cell Parameters In Moderately Anemic Iron-Deficient Pregnant Women Receiving Daily Iron-Folic Acid Supplementation: A Prospective Cohort Study, J. P. Akshaykirthan, Manjunath S. Somannavar, S. Yogeshkumar, M. S. Deepthy, Umesh Charantimath, Amaresh Patil, Mrutyunjaya B. Bellad, Richard Derman, Shivaprasad S. Goudar

Global Health Articles

Background/Objectives: The objective is to study the trajectories of hematologic and biochemical markers in moderately anemic pregnant women receiving oral iron supplementation throughout pregnancy. Methods: This prospective cohort study was conducted from August 2021 to September 2023 involving 315 pregnant women from rural areas of Belgaum, Karnataka, India, with hemoglobin levels between 7.0 and 9.9 g/dL and serum ferritin < 30 ng/mL and/or TSAT < 20%. Participants received iron-folic acid supplementation (IFAS) as per Anaemia Mukt Bharat guidelines. Blood samples were collected to measure various hematologic and iron markers and compared across each visits. Results: We report a complete adherence rate of 95.3% for iron and 97.8% for folic acid supplementation throughout pregnancy and also observed significant improvements in hemoglobin (9.36 (8.55, 9.74) to 12.03 (11.49, 12.72)) g/dL, hematocrit (29.93 ± 2.87 to …

Cardiomyocyte Regeneration Therapy And Its Effect On Lvef And Scar Size- A Systematic Review And Meta-Analysis, Mahnoor Mahnoor, Syed Irtaza Hassan, Muhammad Bakhtiar, Salal Sharjeel, Roha Daneyal, Muhammad Ibrahim, Raheel Iftikhar

Kimmel Cancer Center Faculty Papers

BACKGROUND: Myocardial infarction (MI) results in loss of cardiomyocytes leading to heart failure. Despite advancements in pharmacotherapy and interventions such as revascularization, ischemic heart failure remains a challenge. Recent advancements in stem cell therapies, genetic engineering and bioengineering have shown to improve cardiac function and quality of life.

METHODOLOGY: Following PRISMA guidelines, randomized controlled trials clinical trials from last 12 years were systematically reviewed. All the patients included in these studies had ischemic heart failure and were subjected to different types of stem cell therapies. Protocol for this meta-analysis is registered on PROSPERO (Registration no: CRD42023399263). Data extraction and Quality …

The Effect Of Tranexamic Acid On Blood Coagulation In Primary Total Hip Arthroplasty Using Rotational Thromboelastometry: A Randomized Controlled Trial, Uzung Yoon, David Beausang, Elia Elia, Marc Torjman, Jeffrey Mojica, James J. Purtill, David Nazarian, P. Maxwell Courtney, Yoogoo Kang

Department of Anesthesiology Faculty Papers

BACKGROUND: Tranexamic acid (TXA), is commonly administered prophylactically to reduce blood loss in patients undergoing total hip arthroplasty (THA). However, its effect has never been studied. We hypothesized that no difference exists in the degree of fibrinolysis and blood loss between patients receiving prophylactic TXA and placebo.

METHODS: This double-blinded randomized-controlled trial included 50 patients undergoing primary THA in 2021-2023. Clinicaltrials.gov (NCT03897621). Rotational-thromboelastometry (ROTEM) were performed to test blood coagulability using non citrated whole blood (NATEM) and blood treated with TXA (T-APTEM). The intervention group received TXA intravenously. The placebo group received 0.9% sodium chloride solution. The primary outcome measure …

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And All-Cause Mortality In Patients With Liver Cirrhosis, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, Jose Manuel Martinez Manzano, Andrew Geller, Simone Jarrett, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Kevin Lo, Zurab Azmaiparashvili

Einstein Health Papers

BACKGROUND: Estimated plasma volume status (ePVS) correlates with intravascular congestion and prognosis in patients with heart failure. The ePVS relationship with invasive hemodynamic profiling and clinical outcomes in patients with liver cirrhosis (LC) remains unclear.

METHODS: This single-center retrospective cohort study included LC patients who underwent right heart catheterization (RHC) between 2018 and 2023. Estimated plasma volume status (ePVS) was calculated using the Strauss-derived Duarte formula, with patients classified into high (> 5.5%) and low-ePVS (≤ 5.5%) groups. Cox-multivariable analysis was used to determine if ePVS was associated with all-cause mortality within 1 year post-RHC among transplant-free patients.

RESULTS: Of …

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …

Outcomes Among Heart Failure Patients Hospitalized For Acute Pulmonary Embolism And Covid-19 Infection: Insight From The National Inpatient Sample, Bruce Adrian Casipit, Sahana Tito, Isaac Ogunmola, Abiodun Idowu, Shivaraj Patil, Kevin Lo, Behnam Bozorgnia

Einstein Health Papers

There is paucity of data regarding the outcomes of hospitalized acute pulmonary embolism (PE) patients with heart failure (HF) and Coronavirus Disease 2019 (COVID-19) infection. We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study to investigate the outcomes of hospitalized acute PE patients with HF and COVID-19, looking at its impact on in-hospital mortality, thrombolysis, and thrombectomy utilization as well as hospital length of stay (LOS). A total of 23,413 hospitalized acute PE patients with HF were identified in our study, of which 1.26% (n = 295/23,413) had COVID-19 infection. Utilizing a stepwise survey …

Closed-Loop Modeling Of Central And Intrinsic Cardiac Nervous System Circuits Underlying Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The baroreflex is a multi-input, multi-output physiological control system that regulates blood pressure by modulating nerve activity between the brainstem and the heart. Existing computational models of the baroreflex do not explicitly incorporate the intrinsic cardiac nervous system (ICN), which mediates central control of heart function. We developed a computational model of closed-loop cardiovascular control by integrating a network representation of the ICN within central control reflex circuits. We examined central and local contributions to the control of heart rate, ventricular functions, and respiratory sinus arrhythmia (RSA). Our simulations match the experimentally observed relationship between RSA and lung tidal volume. …

Myosin Heavy Chain And Physiological Adaptation Of The Rat Diaphragm In Elastase-Induced Emphysema., Dong Kwan Kim, Jianliang Zhu, Benjamin W Kozyak, James M Burkman, Neal A Rubinstein, Edward B Lankford, Hansell H Stedman, Taitan Nguyen, Sanford Levine, Joseph B Shrager

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. METHODS: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform …