Medical Specialties Commons^™

Radiolabeled Nanomaterial For Cancer Diagnostics And Therapeutics: Principles And Concepts, Muskan Goel, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

In the last three decades, radiopharmaceuticals have proven their effectiveness for cancer diagnosis and therapy. In parallel, the advances in nanotechnology have fueled a plethora of applications in biology and medicine. A convergence of these disciplines has emerged more recently with the advent of nanotechnology-aided radiopharmaceuticals. Capitalizing on the unique physical and functional properties of nanoparticles, radiolabeled nanomaterials or nano-radiopharmaceuticals have the potential to enhance imaging and therapy of human diseases. This article provides an overview of various radionuclides used in diagnostic, therapeutic, and theranostic applications, radionuclide production through different techniques, conventional radionuclide delivery systems, and advancements in the delivery …

Proton Therapy With Concurrent Chemotherapy For Thoracic Esophageal Cancer: Toxicity, Disease Control, And Survival Outcomes, Michael S Rutenberg, Bradford S Hoppe, Jason S Starr, Ziad Awad, Mathew Thomas, Christopher G Morris, Perry Johnson, Randal H Henderson, Jeremy C Jones, Bharatsinh Gharia, Steven Bowers, Herbert C Wolfsen, Sunil Krishnan, Stephen J Ko, Hani M Babiker, Romaine C Nichols

Faculty, Staff and Student Publications

PURPOSE: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery.

MATERIALS AND METHODS: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton …

Editorial: Modulation Of Microglia Reactivity And Plasticity In Cns Injury, Zhenyan He, Hailiang Tang, Jiping Tang, Xuying He, Ningbo Xu, Devin W Mcbride

Faculty, Staff and Student Publications

No abstract provided.

Challenges And Promise Of Targeting Mirrna In Rheumatic Diseases: A Computational Approach To Identify Mirna Association With Cell Types, Cytokines, And Disease Mechanisms, Farheen S Shaikh, Ruby J Siegel, Aayush Srivastava, David A Fox, Salahuddin Ahmed

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are small non-coding RNAs that alter the expression of target genes at the post-transcriptional level, influencing diverse outcomes in metabolism, cell differentiation, proliferation, cell survival, and cell death. Dysregulated miRNA expression is implicated in various rheumatic conditions, including ankylosing spondylitis (AS), gout, juvenile idiopathic arthritis (JIA), osteoarthritis (OA), psoriatic arthritis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE) and systemic sclerosis. For this review, we used an open-source programming language- PowerShell, to scan the massive number of existing primary research publications on PubMed on miRNAs in these nine diseases to identify and count unique co-occurrences of individual …

In Utero Ethanol Exposure Induces Mitochondrial Dna Damage And Inhibits Mtdna Repair In Developing Brain, Nune Darbinian, Armine Darbinyan, Nana Merabova, Myrna Kassem, Gabriel Tatevosian, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction

Mitochondrial dysfunction is postulated to be a central event in fetal alcohol spectrum disorders (FASD). People with the most severe form of FASD, fetal alcohol syndrome (FAS) are estimated to live only 34 years (95% confidence interval, 31 to 37 years), and adults who were born with any form of FASD often develop early aging. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage, hallmarks of aging, are postulated central events in FASD. Ethanol (EtOH) can cause mtDNA damage, consequent increased oxidative stress, and changes in the mtDNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1). Studies of molecular mechanisms are limited by …

Dna Release From Plant Tissue Using Focused Ultrasound Extraction (Fuse), Alexia Stettinius, Hal Holmes, Qian Zhang, Isabelle Mehochko, Misa Winters, Ruby Hutchison, Adam Maxwell, Jason Holliday, Eli Vlaisavljevich

Faculty, Staff and Student Publications

PREMISE: Sample preparation in genomics is a critical step that is often overlooked in molecular workflows and impacts the success of downstream genetic applications. This study explores the use of a recently developed focused ultrasound extraction (FUSE) technique to enable the rapid release of DNA from plant tissues for genetic analysis.

METHODS: FUSE generates a dense acoustic cavitation bubble cloud that pulverizes targeted tissue into acellular debris. This technique was applied to leaf samples of American chestnut (

RESULTS: We observed that FUSE can extract high quantities of DNA in 9-15 min, compared to the 30 min required for control …

Association Between Giving Birth During The Early Coronavirus Disease 2019 (Covid-19) Pandemic And Serious Maternal Morbidity, Torri D Metz, Rebecca G Clifton, Brenna L Hughes, Grecio J Sandoval, William A Grobman, George R Saade, Tracy A Manuck, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N Simhan, Dwight J Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L Bailit, Maged M Costantine, Harish M Sehdev, Alan T N Tita, George A Macones

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether delivering during the early the coronavirus disease 2019 (COVID-19) pandemic was associated with increased risk of maternal death or serious morbidity from common obstetric complications compared with a historical control period.

METHODS: This was a multicenter retrospective cohort study with manual medical-record abstraction performed by centrally trained and certified research personnel at 17 U.S. hospitals. Individuals who gave birth on randomly selected dates in 2019 (before the pandemic) and 2020 (during the pandemic) were compared. Hospital, health care system, and community risk-mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to the early …

Retroperitoneal Hematoma As An Atypical Presentation Of Choriocarcinoma: A Case Report, Truce Pham, Danica Lapid, Kathleen M Schmeler, J Alejandro Rauh-Hain, Mateo G Leon

Faculty, Staff and Student Publications

A 38-year-old female with an etonogestrel implant in place and history of previous ectopic pregnancy presented with acute abdominal pain and vaginal bleeding. She was found to have a beta-hCG of >12,000 mIU/mL and free fluid noted on a focused assessment with sonography in trauma exam. She underwent an emergent diagnostic laparoscopy due to the suspicion of a ruptured ectopic pregnancy. Findings at the time of surgery included a normal-appearing uterus and left fallopian tube, a surgically absent right fallopian tube and large volume hemoperitoneum with a rapidly expanding left retroperitoneal hematoma. A postoperative computerized tomography (CT) angiogram suggested active …

Editorial: Advances In Mathematical And Computational Oncology, Volume Iii, George Bebis, Mamoru Kato, Mohammad Kohandel, Kathleen Wilkie, Dinler A Antunes, Ken Chen, Jinzhuang Dou

Faculty, Staff and Student Publications

No abstract provided.

Case Report: Responses To The Combination Of Gemcitabine With Sirolimus In Two Patients With Tsc-Mutated Sarcomas, Elise F Nassif, Cissimol P Joseph, Rossana Lazcano, Jocelyn T Joseph, Prapassorn Thirasastr, Alexander J Lazar, Neeta Somaiah

Faculty, Staff and Student Publications

TSC-mutated sarcomas are rare molecular and histologic types of sarcoma. Due to the presence of their specific oncogenic driver mutation, these sarcomas are particularly sensitive to mTOR inhibitors. Recently, nab-sirolimus, an albumin-bound mTOR inhibitor, was approved by the Food and Drug Administration (FDA) for PEComas, which harbor a TSC mutation, and this drug remains the only FDA-approved systemic treatment for these tumors. We report on two cases of patients with TSC-mutated sarcomas who experienced significant responses to the combination of gemcitabine and sirolimus, after progression on prior gemcitabine-based chemotherapy and single agent mTOR inhibition with nab-sirolimus. …

Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most aggressive type of cancer. Its current first-line postsurgery regimens are radiotherapy and temozolomide (TMZ) chemotherapy, both of which are DNA damage-inducing therapies but show very limited efficacy and a high risk of resistance. There is an urgent need to develop novel agents to sensitize GBM to DNA-damaging treatments. Here it is found that the triterpene compound stellettin B (STELB) greatly enhances the sensitivity of GBM to ionizing radiation and TMZ in vitro and in vivo. Mechanistically, STELB inhibits the expression of homologous recombination repair (HR) factors BRCA1/2 and RAD51 by promoting the degradation of PI3Kα …

Mass Spectrometry Based Biomarkers For Early Detection Of Hcc Using A Glycoproteomic Approach, Yehia Mechref, Wenjing Peng, Sakshi Gautam, Parisa Ahmadi, Yu Lin, Jianhui Zhu, Jie Zhang, Suyu Liu, Amit G Singal, Neehar D Parikh, David M Lubman

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%-90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Jo A Rinaudo, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

A Comparative Analysis Of Radical Cystectomy With Perioperative Chemotherapy, Chemoradiation Therapy, Or Systemic Therapy In Patients With Clinically Advanced Node-Positive Bladder Cancer (Cn2/N3), Harshit Garg, Mukund Bhandari, Furkan Dursun, Michael A Liss, Dharam Kaushik, Robert S Svatek, Ahmed M Mansour

Faculty, Staff and Student Publications

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.

Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND …

Return To Sport Following Acl Reconstruction With Slope-Correcting High Tibial Osteotomy In The Elite Athlete, Walter R Lowe, Alfred Mansour, Steven Higbie, Connor Galloway, Jacquelyn Kleihege, Lane Bailey

Faculty, Staff and Student Publications

Background: Increased posterior tibial slope is a strong predictor of anterior cruciate ligament (ACL) graft re-injury. A concomitant slope-reducing high tibial osteotomy (HTO) has been suggested to decrease re-tear risk in these cases although little is known regarding outcomes following ACL reconstruction with HTO, especially in elite athletic patients.

Indications: A 19-year-old National Collegiate Athletics Association (NCAA) Division 1 running back presented with an ACL tear, lateral meniscus tear, and posterior tibial slope of 19° (case 1). A 19-year-old NCAA Division 1 soccer forward presented with an ACL graft re-tear and posterior tibial slope of 21° (case 2).

Technique: Anterior …

Increasing Rates Of Ulnar Collateral Ligament Repair Outpace Reconstruction In Isolated Injuries: Review Of A Texas Surgical Database, Taylor J Willenbring, Eden C Epner, Ryan J Warth, James M Gregory

Faculty, Staff and Student Publications

BACKGROUND: The gold standard of treatment for ulnar collateral ligament (UCL) injuries has been reconstruction. Despite early repair studies yielding less than satisfactory results, there has been recent renewed interest in UCL repair due to improved outcomes and new technologies. Data regarding clinical use of these procedures are lacking. The purpose of this study was to define the epidemiological trends of UCL repair and reconstruction surgery from 2010 to 2019, compare demographic characteristics of patients undergoing either procedure, and determine incidence of concomitant procedures in each surgical group as well as comparing respective patient-level charges.

METHODS: A retrospective database analysis …

Editorial: Women In Molecular And Cellular Oncology, Petranel T Ferrao, Laura Rosanò, Valeria Poli, Shilpa S Dhar, Ana Paula Lepique

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Women In Molecular And Cellular Oncology, Volume Ii: 2022, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

Self-Administered Transcranial Direct Current Stimulation Treatment Of Knee Osteoarthritis Alters Pain-Related Fnirs Connectivity Networks, Samuel Montero-Hernandez, Luca Pollonini, Lindsey Park, Geraldine Martorella, Hongyu Miao, Kenneth B Mathis, Hyochol Ahn

Faculty, Staff and Student Publications

SIGNIFICANCE: Knee osteoarthritis (OA) is a disease that causes chronic pain in the elderly population. Currently, OA is mainly treated pharmacologically with analgesics, although research has shown that neuromodulation via transcranial direct current stimulation (tDCS) may be beneficial in reducing pain in clinical settings. However, no studies have reported the effects of home-based self-administered tDCS on functional brain networks in older adults with knee OA.

AIM: We used functional near-infrared spectroscopy (fNIRS) to investigate the functional connectivity effects of tDCS on underlying pain processing mechanisms at the central nervous level in older adults with knee OA.

APPROACH: Pain-related brain connectivity …

Editorial: Advanced Bioremediation Technologies And Processes For The Treatment Of Synthetic Organic Compounds (Socs), Volume Ii, Kunal R Jain, Chirayu Desai, Eric D Van Hullebusch, Datta Madamwar

Faculty, Staff and Student Publications

No abstract provided.

A Steadier Hand: The First Human Clinical Trial Of A Single-Use Robotic-Assisted Surgical Device For Cochlear Implant Electrode Array Insertion, Jay A Gantz, Bruce J Gantz, Christopher R Kaufmann, Allan M Henslee, Camille C Dunn, Xiaoyang Hua, Marlan R Hansen

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the safety and utility of an investigational robotic-assisted cochlear implant insertion system.

STUDY DESIGN: Prospective, single-arm, open-label study under abbreviated Investigational Device Exemption requirements.

SETTING: All procedures were performed, and all data were collected, at a single tertiary referral center.

PATIENTS: Twenty-one postlingually deafened adult subjects that met Food and Drug Administration indication criteria for cochlear implantation.

INTERVENTION: All patients underwent standard-of-care surgery for unilateral cochlear implantation with the addition of a single-use robotic-assisted insertion device during cochlear electrode insertion.

MAIN OUTCOME MEASURES: Successful insertion of cochlear implant electrode array, electrode array insertion time, postoperative implant function. …

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …

Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans

Faculty, Staff and Student Publications

No abstract provided.

Futility In Acute Care Surgery: First Do No Harm, Melissa Hornor, Uzer Khan, Michael W Cripps, Allyson Cook Chapman, Jennifer Knight-Davis, Thaddeus J Puzio, Bellal Joseph

Faculty, Staff and Student Publications

The consequences of the delivery of futile or potentially ineffective medical care and interventions are devastating on the healthcare system, our patients and their families, and healthcare providers. In emergency situations in particular, determining if escalating invasive interventions will benefit a frail and/or severely critically ill patient can be exceedingly difficult. In this review, our objective is to define the problem of potentially ineffective care within the specialty of acute care surgery and describe strategies for improving the care of our patients in these difficult situations.

A Large Screen Identifies Beta-Lactam Antibiotics Which Can Be Repurposed To Target The Syphilis Agent, Kathryn A Hayes, Jules M Dressler, Steven J Norris, Diane G Edmondson, Brandon L Jutras

Faculty, Staff and Student Publications

Syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (hereafter called T. pallidum), is re-emerging as a worldwide sexually transmitted infection. A single intramuscular dose of benzathine penicillin G is the preferred syphilis treatment option. Both supply shortage concerns and the potential for acquired antibiotic resistance further the need to broaden the repertoire of syphilis therapeutics. We reasoned that other β-lactams may be equally or more effective at targeting the disease-causing agent, Treponema pallidum, but have yet to be discovered due to a previous lack of a continuous in vitro culture system. Recent technical advances with respect to …

Epigenetic Aging In Psychiatry: Clinical Implications And Therapeutic Opportunities, Camila N C Lima, Gabriel R Fries

Faculty, Staff and Student Publications

No abstract provided.

Clonal Isolates Of Treponema Pallidum Subsp Pallidum Nichols Provide Evidence For The Occurrence Of Microevolution During Experimental Rabbit Infection And In Vitro Culture, Diane G Edmondson, Bridget D De Lay, Blake M Hanson, Lindsay E Kowis, Steven J Norris

Faculty, Staff and Student Publications

The recent development of a system for long-term in vitro culture of the syphilis spirochete, Treponema pallidum subsp. pallidum, has introduced the possibility of detailed genetic analysis of this bacterium. In this study, the in vitro culture system was used to isolate and characterize clonal populations of T. pallidum subsp. pallidum Nichols, the most widely studied strain. In limiting dilutions experiments, it was possible to establish cultures with inocula as low as 0.5 T. pallidum per well despite the long generation time (~35 to 40 hours) of this organism. Six Nichols strain clones isolated by limiting dilution were characterized in …

Extensive Fibrosis In Mediastinal Seminoma Is A Diagnostic Pitfall In Small Biopsies: Two Case Reports, Anthony R Liccardi, Kristen Thomas, Navneet Narula, Lea Azour, Andre L Moreira, Fang Zhou

Faculty, Staff and Student Publications

Background

In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms.

Cases Description

We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In …

Exceptional Response To Pembrolizumab For Treatment Of Metastatic Chemorefractory Endometrial Carcinoma In A Patient With Lynch Syndrome: A Case Report, Samantha Batman, J Alejandro Rauh-Hain, Michaela Onstad Grinsfelder, Ross Harrison, Monica Avila, Han Cun, Jeffrey Andrew How, Nidhi Tandon, Xiaohong Wang, Emily Hinchcliff, Amir Anthony Jazaeri, Kathleen M Schmeler

Faculty, Staff and Student Publications

Advanced endometrial cancer is associated with poor outcomes and few treatment options exist. Recently, the US Federal Drug Administration approved pembrolizumab for the treatment of endometrial cancers that are deficient in mismatch repair and have high microsatellite instability (MSI). Lynch syndrome is an autosomal dominant disease that causes MSI-high endometrial cancer. We report a case of a 46-year-old woman with Lynch syndrome and advanced endometrial cancer who experienced progressive disease after treatment with chemotherapy with carboplatin and paclitaxel. She was then treated with single-agent pembrolizumab and had an exceptional response. She was noted to have a significant decrease in the …

Case Report: Immune Checkpoint Inhibitor-Induced Multiorgan Vasculitis Successfully Treated With Rituximab, Sehrish Qureshi, Naszrin Arani, Vishnu Parvathareddy, Amanda Tchakarov, Maen Abdelrahim, Maria Suarez-Almazor, Jianjun Zhang, Don Lynn Gibbons, John Heymach, Mehmet Altan, Ala Abudayyeh

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. ICIs have a unique side effect profile, generally caused by inflammatory tissue damage, with clinical features similar to autoimmune conditions. Acute kidney injury from ICIs has been well studied; incidence ranges from 1% to 5%, with higher incidence when combination ICI therapies are used. Although the overall reported incidence of ICI-associated glomerulonephritis is less than 1%, vasculitis is the most commonly reported ICI-related glomerulonephritis. Other biopsy findings include thrombotic microangiopathy, focal segmental glomerulosclerosis, minimal change disease, and IgA nephropathy with secondary amyloidosis. We report a case in which a woman …