Internal Medicine Commons^™

Targeting Myocardial Equilibrative Nucleoside Transporter Ent1 Provides Cardioprotection By Enhancing Myeloid Adora2b Signaling, Jiaojiao Wang, Andre R Jordan, Huabin Zhu, Sarrah L Hasanali, Eric Thomas, Soum D Lokeshwar, Daley S Morera, Sung Alexander, Joseph Mcdaniels, Anuj Sharma, Karina Aguilar, Semih Sarcan, Tianyi Zhu, Mark S Soloway, Martha K Terris, Muthusamy Thangaraju, Luis E Lopez, Vinata B Lokeshwar

Faculty, Staff and Student Publications

BACKGROUND: Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment.

METHODS: We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and …

Intestinal Iga-Coated Bacteria In Healthy- And Altered-Microbiomes (Dysbiosis) And Predictive Value In Successful Fecal Microbiota Transplantation, Herbert L Dupont, Zhi-Dong Jiang, Ashley S Alexander, Andrew W Dupont, Eric L Brown

Faculty, Staff and Student Publications

IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of …

Case Study: Abnormal Presentation Of Infective Endocarditis With Streptococcus Canis And Chiari Network, Shahbaz Afzal, Ryan Russell, Alexander Chekhov

Advances in Clinical Medical Research and Healthcare Delivery

Here we present a rare case of infective endocarditis (IE) with Streptococcus canis and Chiari network in an 85 year old female living with multiple dogs and open skin of lower extremity predisposing her to bacteremia. Underlying abnormalities of the cardiac chambers such as Chiari network predisposes to a higher incidence of bacterial seeding and causing IE. A Chiari network is usually asymptomatic and of no clinical significance but can worsen prognosis in IE. IE carries a significant morbidity and mortality burden and when diagnosed early can be a lifesaving diagnosis. Due to the wide range of complications, early diagnosis …

Labial Frenotomy For Symptomatic Isolated Upper Lip Tie, Cecilia G Freeman, Jason F Ohlstein, Nicholas A Rossi, John B Mcintire, Luis D Neve, Shiva Daram, Harold S Pine

Faculty, Staff and Student Publications

BACKGROUND: The benefits and challenges of successful breastfeeding for both mother and child have been well-established in the literature. While ankyloglossia, or tongue tie, alone or in combination with upper lip tie has been the focus of several previous studies, very few have directly addressed isolated symptomatic upper lip tie and the role of surgical correction for breastfeeding difficulties.

MATERIALS AND METHODS: Seven infants with isolated upper lip tie and breastfeeding difficulty were taken to the operating room for labial frenotomy. These infants were assessed at their follow-up visits for their degree of weight gain since their procedure. Their mothers …

The Importance Of Mitral Valve Prolapse Doming Volume In The Assessment Of Left Ventricular Stroke Volume With Cardiac Mri, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.

METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of …

Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Hanh Hong Chu, Yoshiki Kobayashi, Dan Van Bui, Yasutaka Yun, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Akira Kanda, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …

High-Frequency Ultrasound In Patients With Seronegative Rheumatoid Arthritis, Junkui Wang, Miao Wang, Qinghua Qi, Zhibin Wu, Jianguo Wen

Faculty, Staff and Student Publications

This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The …

Procedural Outcomes After Percutaneous Coronary Interventions In Focal And Diffuse Coronary Artery Disease, Takuya Mizukami, Jeroen Sonck, Koshiro Sakai, Brian Ko, Michael Maeng, Hiromasa Otake, Bon-Kwon Koo, Sakura Nagumo, Bjarne L Nørgaard, Jonathon Leipsic, Toshiro Shinke, Daniel Munhoz, Niya Mileva, Marta Belmonte, Hirofumi Ohashi, Emanuele Barbato, Nils P Johnson, Bernard De Bruyne, Carlos Collet

Faculty, Staff and Student Publications

Background

Coronary artery disease (CAD) patterns play an essential role in the decision‐making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes.

Methods and Results

This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post‐PCI FFR >0.90 was considered an optimal result. …

Detection Of Progression Or Regression Of Breast Cancer By Circulating Tumor Dna (Ctdna), Ujjwal Karki, Bipin Ghimire, Emma Herrman, Siddhartha Yadav, Mohammad Muhsin Chisti

Conference Presentation Abstracts

Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into the systemic circulation. Studies have shown potential utility of the test to predict relapse or recurrence following treatment in solid tumors, but sensitivity and specificity have varied widely, ranging from 19-100% and 80-100% respectively, in breast cancer specifically. Moreover, literature describing the utility of monitoring dynamic changes in ctDNA trends is limited. We aim to evaluate the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings.

Treatment Of Epilepsy Using A Targeted P38Γ Kinase Gene Therapy, Nicolle Morey, Magdalena Przybyla, Julia Van Der Hoven, Yazi D Ke, Fabien Delerue, Janet Van Eersel, Lars M Ittner

Faculty, Staff and Student Publications

Hyperphosphorylated microtubule-associated protein tau has been implicated in dementia, epilepsy, and other neurological disorders. In contrast, site-specific phosphorylation of tau at threonine 205 (T205) by the kinase p38γ was shown to disengage tau from toxic pathways, serving a neuroprotective function in Alzheimer's disease. Using a viral-mediated gene delivery approach in different mouse models of epilepsy, we show that p38γ activity-enhancing treatment reduces seizure susceptibility, restores neuronal firing patterns, reduces behavioral deficits, and ameliorates epilepsy-induced deaths. Furthermore, we show that p38γ-mediated phosphorylation of tau at T205 is essential for this protection in epilepsy, as a lack of this critical interaction reinstates …

Exploring The Experiences Of Clients Receiving Opioid Use Disorder Treatment At A Methadone Clinic In Kenya: A Qualitative Study, Sarah Kiburi, Jackline Mwangi, Geoffrey Maina

Internal Medicine, East Africa

Background: Assessing the experiences of individuals on methadone treatment is essential to help evaluate the treatment program’s efectiveness. This study aimed to explore the experiences of patients receiving methadone treatment at a clinic in Nairobi, Kenya.

Method: This study employed an exploratory qualitative study design. Through purposive sampling, participants were enrolled from individuals attending a methadone clinic for at least 2 years. Semi-structured individual interviews were used to collect data on substance use and experience before methadone treatment and experiences after starting methadone treatment, including benefts and challenges. Interviews were transcribed, and NVIVO 12 software was used to …

Intensivist -Driven Ventilator Management Shortens Duration Of Mechanical Ventilation In Coronary Artery Bypass Graft Surgery Patients, Yonatan Dollin, Brian Elliott, Ronald J. Markert, Angela Morman, Matthew Koroscil

Internal Medicine Faculty Publications

Background Prolonged mechanical ventilation in post Coronary Artery Bypass Graft Surgery (CABG) is associated with deleterious effects including, increased ICU and hospital length of stay (LOS), infectious complications, and mortality. Standardized ventilator weaning protocols and the utilization of critical care physicians in post CABG patient care vary substantially among institutions. The purpose of this study was to evaluate if intensivist consultation in conjunction with a multidisciplinary, standardized ventilator weaning protocol improves outcomes in CABG patients. Materials and Methods We performed a single-center, retrospective, before-after cohort analysis at Miami Valley Hospital in Dayton, OH, a 970-bed community hospital. Patients were divided …

An Unexpected Case Of Non-Uremic Calciphylaxis In A Patient With Multiple Risk Factors, Shannon Nugent, Fred Karaisz, Maisa Elbadawi, Andrew Touati, Neda Nikbakht, Jason B. Lee, Hasan Arif

Division of Internal Medicine Faculty Papers & Presentations

A 58-year-old woman with a history of morbid obesity, asthma, and prior warfarin use presented to the hospital with shortness of breath and a three-month history of painful, ulcerated ulcers with retiform purpura of her bilateral distal extremities. A punch biopsy specimen demonstrated focal necrosis and hyalinization of the adipose tissue with subtle arteriolar calcium deposition, findings consistent with calciphylaxis. We discuss the presentation of non-uremic calciphylaxis and review the risk factors, pathophysiology, and interdisciplinary management approach of this rare disease.

Fulminant Lung Fibrosis In Non-Resolvable Covid-19 Requiring Transplantation, Soma S K Jyothula, Andrew Peters, Yafen Liang, Weizhen Bi, Pooja Shivshankar, Simon Yau, Puneet S Garcha, Xiaoyi Yuan, Bindu Akkanti, Scott Collum, Nancy Wareing, Rajarajan A Thandavarayan, Fernando Poli De Frias, Ivan O Rosas, Bihong Zhao, L Maximilian Buja, Holger K Eltzschig, Howard J Huang, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We …

Luspatercept In Low-Risk Myelodysplastic Syndrome: A Real-World Single Institution Case Series, Shamis Khan, Sara Taveras Alam, Rosa Torres Ramos, John Etumbani Mbue, Effrosyni Apostolidou, Gustavo A Rivero, Sarvari Venkata Yellapragada

Faculty, Staff and Student Publications

No abstract provided.

Secondhand Smoke Exposure Is Independently Associated With Stroke Among Non-Smoking Adults In West Africa., Akinkunmi Paul Okekunle, Osahon Jeffery Asowata, Adekunle G. Fakunle, Onoja Matthew Akpa, Fred S. Sarfo, Albert Akpalu, Kolawole Wahab, Reginald Obiako, Morenikeji Komolafe, Philip Adebayo

Internal Medicine, East Africa

Background: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans.

Objective: To evaluate the association of SHSE with stroke among indigenous Africans. Methods We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05.

Results: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes.

Conclusion: …

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Reproducing Statistics Performed In Published Randomized Controlled Trials, Naila H Dhanani, Oscar A Olavarria, Cynthia S Bell, Julie L Holihan, Mike K Liang

Faculty, Staff and Student Publications

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.

METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. …

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty, Staff and Student Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty, Staff and Student Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …