Diseases Commons^™

Reconstructive Outcomes Of Multilayered Closure Of Large Skull Base Dural Defects Following Open Anterior Craniofacial Resection, Justin Shi, Tokunbo Ayeni, Kathleen Kelly Gallagher, Akash J Patel, Ali Jalali, David J Hernandez, Angela D Haskins, Vlad C Sandulache, Erich M Sturgis, Andrew T Huang

Faculty, Staff and Students Publications

Introduction  Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities.

Design  This study is a retrospective review.

Results  Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm ² . Dural graft matrices …

Pathological Implication Of Protein Post-Translational Modifications In Cancer, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Protein post-translational modifications (PTMs) profoundly influence protein functions and play crucial roles in essentially all cell biological processes. The diverse realm of PTMs and their crosstalk is linked to many critical signaling events involved in neoplastic transformation, carcinogenesis and metastasis. The pathological roles of various PTMs are implicated in all aspects of cancer hallmark functions, cancer metabolism and regulation of tumor microenvironment. Study of PTMs has become an important area in cancer research to understand cancer biology and discover novel biomarkers and therapeutic targets. With a limited scope, this review attempts to discuss some PTMs of high frequency with recognized …

Exome Sequencing Identifies Genetic Variants In Anophthalmia And Microphthalmia, Jingjing Li, Wei Yang, Yuejun Jessie Wang, Chen Ma, Cynthia J Curry, Daniel Mcgoldrick, Deborah A Nickerson, Jessica X Chong, Elizabeth E Blue, James C Mullikin, Jennita Reefhuis, Wendy N Nembhard, Paul A Romitti, Martha M Werler, Marilyn L Browne, Andrew F Olshan, Richard H Finnell, Marcia L Feldkamp, Faith Pangilinan, Lynn M Almli, Mike J Bamshad, Lawrence C Brody, Mary M Jenkins, Gary M Shaw, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 …

Glutathione Peroxidase 2 Is A Metabolic Driver Of The Tumor Immune Microenvironment And Immune Checkpoint Inhibitor Response, Kazi Mokim Ahmed, Ratna Veeramachaneni, Defeng Deng, Nagireddy Putluri, Vasanta Putluri, Maria F Cardenas, David A Wheeler, William K Decker, Andy I Frederick, Sawad Kazi, Andrew G Sikora, Vlad C Sandulache, Mitchell J Frederick

Faculty, Staff and Students Publications

BACKGROUND: The existence of immunologically 'cold tumors' frequently found across a wide spectrum of tumor types represents a significant challenge for cancer immunotherapy. Cold tumors have poor baseline pan-leukocyte infiltration, including a low prevalence of cytotoxic lymphocytes, and not surprisingly respond unfavorably to immune checkpoint (IC) inhibitors. We hypothesized that cold tumors harbor a mechanism of immune escape upstream and independent of ICs that may be driven by tumor biology rather than differences in mutational neoantigen burden.

METHODS: Using a bioinformatic approach to analyze TCGA (The Cancer Genome Atlas) RNA sequencing data we identified genes upregulated in cold versus hot …

Advances In Management And Therapeutics Of Cutaneous Basal Cell Carcinoma, Olivia M Chen, Keemberly Kim, Chelsea Steele, Kelly M Wilmas, Nader Aboul-Fettouh, Carrick Burns, Hung Quoc Doan, Sirunya Silapunt, Michael R Migden

Faculty, Staff and Student Publications

Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary versus recurrent tumor, anatomic location, size, and patient attributes determine the risk level and acceptable treatment options. Surgical options offer histologic confirmation of tumor clearance. Standard excision provides post-treatment histologic assessment, while Mohs micrographic surgery (MMS) provides complete margin assessment intraoperatively. Additional treatment options may be employed in the correct clinical context. Small and low-risk BCCs, broad field cancerization, locally-advanced disease, metastatic disease, cosmetic concerns, or morbidity with surgical …

Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott

Faculty, Staff and Students Publications

Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell "glucolipotoxicity" can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is …

Effect Of A Glp-1 Mimetic On The Insulin Response To Oral Sugar Testing In Horses, Darko Stefanovski, Mary A Robinson, Andrew Van Eps

Faculty, Staff and Student Publications

BACKGROUND: Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed.

HYPOTHESIS/OBJECTIVES: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations.

STUDY DESIGN: Randomized, crossover, experimental study.

ANIMALS: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID).

METHODS: Horses completed both study arms: subcutaneous administration of exenatide (or no treatment) 30 min before an oral sugar …

Stem Cell Transplantation For Systemic Sclerosis, Sebastian Bruera, Harish Sidanmat, Donald A Molony, Maureen D Mayes, Maria E Suarez-Almazor, Kate Krause, Maria Angeles Lopez-Olivo

Faculty, Staff and Students Publications

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.

OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).

SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February …

Whole Genome Sequence Association Analysis Of Fasting Glucose And Fasting Insulin Levels In Diverse Cohorts From The Nhlbi Topmed Program, Daniel Dicorpo, Sheila M. Gaynor, Emily M. Russell, Kenneth E. Westerman, Laura M. Raffield, Marcio Almeida, Juan M. Peralta, John Blangero, Joanne E. Curran, Ravindranath Duggirala

School of Medicine Publications

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well …

Advances In Cutaneous Squamous Cell Carcinoma Management, Carrick Burns, Shelby Kubicki, Quoc-Bao Nguyen, Nader Aboul-Fettouh, Kelly M Wilmas, Olivia M Chen, Hung Quoc Doan, Sirunya Silapunt, Michael R Migden

Faculty, Staff and Student Publications

cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of …

Heart Failure In General And Cardiac Transplant Patients With Covid-19, Munish Sharma, Gowthami Sai Kogilathota Jagirdhar, Kalpalatha K Guntupalli, Rahul Kashyap, Salim Surani

Faculty, Staff and Students Publications

Coronavirus disease 2019 (COVID-19) is primarily an infection of the respiratory tract, but it can have multisystem manifestations. Cardiac complications of COVID-19 can range from acute myocardial injury, cardiac arrhythmias, or heart failure, amongst others. Heart failure (HF) in COVID-19 can be a de novo process or due to worsening of pre-existing cardiovascular ailment. HF in a patient with COVID-19 not only poses challenges in clinical presentation and management of COVID-19 but also affect prognosis of the patient. This article aims to succinctly revisit the implications of this pandemic regarding pre-existing HF or new-onset HF based on prevailing data. It …

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …

A Phospholipid Mimetic Targeting Lrh-1 Ameliorates Colitis, Suzanne G Mays, Emma H D'Agostino, Autumn R Flynn, Xiangsheng Huang, Guohui Wang, Xu Liu, Elizabeth J Millings, C Denise Okafor, Anamika Patel, Michael L Cato, Jeffery L Cornelison, Diana Melchers, René Houtman, David D Moore, John W Calvert, Nathan T Jui, Eric A Ortlund

Faculty, Staff and Students Publications

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

Pneumonitis After Immune Checkpoint Inhibitor Therapies In Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study, Ajay Sheshadri, Alberto A Goizueta, Vickie R Shannon, David London, Guillermo Garcia-Manero, Hagop M Kantarjian, Farhad Ravandi-Kashani, Tapan M Kadia, Marina Y Konopleva, Courtney D Dinardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A Albittar, Linda L Zhong, Fechukwu O Akhmedzhanov, Muhammad H Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R Mendoza, Myrna C B Godoy, Girish Shroff, Sang T Kim, Saadia A Faiz, Dimitrios P Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G Daver

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Genetic Risk, Midlife Life's Simple 7, And Incident Dementia In The Atherosclerosis Risk In Communities Study, Adrienne Tin, Jan Bressler, Jeannette Simino, Kevin J Sullivan, Hao Mei, B Gwen Windham, Michael Griswold, Rebecca F Gottesman, Eric Boerwinkle, Myriam Fornage, Thomas H Mosley

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher scores in Life's Simple 7 (LS7), a metric for cardiovascular and brain health, have been associated with lower risk of dementia. It is uncertain whether this association holds among those with high genetic risk of dementia. Our objective is to evaluate the extent that LS7 may offset dementia risk across the range of genetic risk.

METHODS: Participants in the Atherosclerosis Risk in Communities (ARIC) Study were followed from 1987-1989 to 2019. We derived midlife LS7 scores and generated genetic risk scores (GRS) using genome-wide summary statistics of Alzheimer disease, which have been used to study the …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

An Evaluation Of A Multidisciplinary Implementation Of Evidence Based Practice In Prediabetes, Emily Sisco

Dissertations

Abstract

Problem Over 70% of prediabetic patients progress to full diabetes. There are over 80 million American adults who are diabetic. Diabetes is the costliest chronic disease that often leads to many other health issues.

Methods This QI project utilized a descriptive observational design. Quantitative data was collected via retrospective chart review. Primary data collected was documentation of a patient visit to the registered dietician and the hemoglobin A1c (HbA1c) of patients who followed up in the office after the referral.

Results Eight patients followed up to the office for a second visit (n=8). Four patients did see the registered …

Selected Transesophageal Echocardiographic Parameters Of Left Ventricular Diastolic Function Predict Length Of Stay Following Coronary Artery Bypass Graft-A Prospective Observational Study, Samhati Mondal, Nauder Faraday, Wei Dong Gao, Sarabdeep Singh, Sachidanand Hebbar, Kimberly N Hollander, Thomas S Metkus, Lee A Goeddel, Maria Bauer, Brian Bush, Brian Cho, Stephanie Cha, Stephanie O Ibekwe, Domagoj Mladinov, Noah S Rolleri, Laeben Lester, Jochen Steppan, Rosanne Sheinberg, Nadia B Hensley, Anubhav Kapoor, Jeffrey M Dodd-O

Faculty, Staff and Students Publications

(1) Importance: Abnormal left ventricular (LV) diastolic function, with or without a diagnosis of heart failure, is a common finding that can be easily diagnosed by intra-operative transesophageal echocardiography (TEE). The association of diastolic function with duration of hospital stay after coronary artery bypass (CAB) is unknown. (2) Objective: To determine if selected TEE parameters of diastolic dysfunction are associated with length of hospital stay after coronary artery bypass surgery (CAB). (3) Design: Prospective observational study. (4) Setting: A single tertiary academic medical center. (5) Participants: Patients with normal systolic function undergoing isolated CAB from September 2017 through June 2018. …

Long-Term Follow-Up For The Development Of Subsequent Malignancies In Patients Treated With Genetically Modified Iecs, David H M Steffin, Ibrahim N Muhsen, Laquisa C Hill, Carlos A Ramos, Nabil Ahmed, Meenakshi Hegde, Tao Wang, Mengfen Wu, Stephen Gottschalk, Sarah B Whittle, Premal D Lulla, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Andras Heczey, Leonid S Metelitsa, Bambi J Grilley, Catherine Robertson, Virginia Torrano, Natalia Lapteva, Adrian P Gee, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop

Faculty, Staff and Students Publications

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, …

Evaluation Of A Process Change Using An Updated Sedation Protocol, Rachel Allen

Dissertations

Problem: Pediatric delirium is continuing to increase intensive care environments and for patients who require mechanical ventilation and continuous sedative medications. Delirium is harmful to the patient creating lasting neurologic and mental health issues along with prolonged hospitalization and increased healthcare cost

Method: For this quality improvement (QI) project, a descriptive observational study was used to evaluate the implementation of a sedation protocol for patients who are mechanically ventilated and on continuous sedative medications. This was completed with the use of retrospective chart reviews three months prior to implementation and three months after the new protocol was implemented. Nurses were …

Synthetic Essentiality Of Tryptophan 2,3-Dioxygenase 2 In Apc-Mutated Colorectal Cancer, Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A Labella, Jing Li, Denise J Spring, Di Zhao, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Inactivation of adenomatous polyposis coli (APC) is common across many cancer types and serves as a critical initiating event in most sporadic colorectal cancers. APC deficiency activates WNT signaling, which remains an elusive target for cancer therapy, prompting us to apply the synthetic essentiality framework to identify druggable vulnerabilities for APC-deficient cancers. Tryptophan 2,3-dioxygenase 2 (TDO2) was identified as a synthetic essential effector of APC-deficient colorectal cancer. Mechanistically, APC deficiency results in the TCF4/β-catenin-mediated upregulation of TDO2 gene transcription. TDO2 in turn activates the Kyn-AhR pathway, which increases glycolysis to drive anabolic cancer cell growth and CXCL5 secretion to recruit …

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …

Multifaceted Intervention To Improve P2y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial, P Michael Ho, Colin I O'Donnell, Marina Mccreight, Anthony A Bavry, Hayden B Bosworth, Saket Girotra, P Michael Grossman, Christian Helfrich, Faisal Latif, David Lu, Michael Matheny, Kreton Mavromatis, Jose Ortiz, Amitabh Parashar, Devona M Ratliff, Gary K Grunwald, Michael Gillette, Hani Jneid

Faculty, Staff and Students Publications

Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) …

Pathophysiology Of Aortic Stenosis, Melissa Lee

Nursing Student Class Projects (Formerly MSN)

Pathophysiology of Aortic Stenosis

Melissa J. Lee

Department of Nursing, Otterbein University

NURS 6810: Advanced Pathophysiology for the Advanced Practice Nurse

Dr. Deana Batross & Dr. Shivani Bhatnagar

July 29, 2022

Pathophysiology of Aortic Stenosis

Proper evaluation of co-morbidities is imperative for patient safety and successful outcomes for patients undergoing anesthesia. Aortic stenosis (AS) is one of the most complex diseases encountered in anesthesia, affecting five percent of older adults and ten percent of the 80-89-year-old-cohort (Joseph et al., 2017). The pathophysiological development of AS is the end result of an inflammatory process caused by endothelial damage from mechanical stress, …

Perioperative Risks Of The Patient With Heart Failure, Gabrielle Metoyer

Nursing Student Class Projects (Formerly MSN)

Perioperative Risks of the Patient with Heart Failure

Gabrielle Metoyer

Department of Nursing, Otterbein University

NURS 6810 – Advanced Pathophysiology

Dr. Deanna Batross and Dr. Shivani Bhatnagar

August 5, 2022

Abstract

According to the CDC (2020), heart failure occurs when the heart cannot pump enough blood and oxygen to support other organs in your body. Heart failure is an epidemic disease affecting 1-2% of the population worldwide (Schwinger, 2020). It is one of the leading causes of morbidity and mortality worldwide with an estimated 6.5 million adults with heart failure in the United States (Lo et al., 2021). Medical advances …

Cardiovascular Disease Awareness Program On Risk Factors For Cardiovascular Disease Among Adolescents In Selected Schools, In New Delhi, Komal Kumari

Manipal Journal of Nursing and Health Sciences

Introduction: Cardiovascular disease (CVD) is the main cause of mortality worldwide. The main risk factors include tobacco chewing/smoking, higher blood cholesterol, high blood pressure, physical inactivity, obesity, excessive alcohol use, age, sex, and heredity. Although CVDs commonly develop in middle age or later, risk factors are highly impacted by childhood practices that are continued into maturity. Knowledge gaps on CVD and its risk factors are major obstacles to effective prevention and treatment. Hence, a CVD awareness program was organized in order to educate adolescents about CVD and its risk factors. Objective: The objectives of the study were to identify students’ …

Complex And Simple Appendicitis: Restrictive Or Liberal Postoperative Antibiotic Exposure (Casa Relax) Using Desirability Of Outcome Ranking (Door) And Response Adjusted For Duration Of Antibiotic Risk (Radar): Study Protocol For A Randomized Controlled Trial, Daniel Dante Yeh, Gabrielle E Hatton, Claudia Pedroza, Gerd Pust, Alejandro Mantero, Nicholas Namias, Lillian S Kao

Faculty, Staff and Student Publications

OBJECTIVES: After appendectomy for simple or complicated appendicitis, the optimal duration of postoperative antibiotics (postop abx) is unclear and great practice variability exists. We propose to compare restrictive versus liberal postop abx using a hierarchical composite endpoint which includes patient-centered outcomes and accounts for duration of antibiotic exposure.

METHODS/DESIGN: Participants with simple or complicated appendicitis undergoing appendectomy are randomly assigned to either restricted or liberal strategy. Eligible subjects declining randomization will be recruited to enroll in an observation only cohort. The primary endpoint is an ordinal scale of mutually exclusive clinical outcomes with within-category rankings determined by duration of antibiotic …

Comparison Of Different Metrics Of Cerebral Autoregulation In Association With Major Morbidity And Mortality After Cardiac Surgery, Xiuyun Liu, Joseph Donnelly, Ken M Brady, Kei Akiyoshi, Brian Bush, Raymond C Koehler, Jennifer K Lee, Charles W Hogue, Marek Czosnyka, Peter Smielewski, Charles H Brown

Faculty, Staff and Student Publications

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery.

METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. …