Digital Commons Network^™

Lost In Translation: A Disconnect Between The Science And Medicare Coverage Criteria For Continuous Subcutaneous Insulin Infusion, Grazia Aleppo, Christopher G Parkin, Anders L Carlson, Rodolfo J Galindo, Davida F Kruger, Carol J Levy, Guillermo E Umpierrez, Gregory P Forlenza, Janet B Mcgill

Open Access Publications

Numerous studies have demonstrated the clinical value and safety of insulin pump therapy in type 1 diabetes and type 2 diabetes populations. However, the eligibility criteria for insulin pump coverage required by the Centers for Medicare & Medicaid Services (CMS) discount conclusive evidence that supports insulin pump use in diabetes populations that are currently deemed ineligible. This article discusses the limitations and inconsistencies of the insulin pump eligibility criteria relative to current scientific evidence and proposes workable solutions to address this issue and improve the safety and care of all individuals with diabetes.

Upstaging And Survival Outcomes For Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results From The International Robotic Cystectomy Consortium, Umar Iqbal, Eric Kim, Et Al

Open Access Publications

No abstract provided.

Augmented Reality In Spinal Surgery: Highlights From Augmented Reality Lectures At The Emerging Technologies Annual Meetings, Syed-Abdullah Uddin, George Hanna, Lindsey Ross, Camilo Molina, Timur Urakov, Patrick Johnson, Terrence Kim, Doniel Drazin

Open Access Publications

Introduction Augmented reality (AR) is an advanced technology and emerging field that has been adopted into spine surgery to enhance care and outcomes. AR superimposes a three-dimensional computer-generated image over the normal anatomy of interest in order to facilitate visualization of deep structures without the ability to directly see them. Objective To summarize the latest literature and highlight AR from the annual "Spinal Navigation, Emerging Technologies and Systems Integration" meeting lectures presented by the Seattle Science Foundation (SSF) on the development and use of augmented reality in spinal surgery. Methods We performed a comprehensive literature review from 2016 to 2020 …

Recognizing The Vulnerable: Perspectives, Attitudes, And Interests Of Women With Uterine Factor Infertility Towards Uterus Allotransplantation, Helen Xun, Darya Fadavi, Halley Darrach, Nicole Fischer, Pooja Yesantharao, Franca Kraenzlin, Amanda Nickles Fader, James H. Segars, Justin M. Sacks

Open Access Publications

BACKGROUND: Uterine allotransplantation (UTx) is a novel therapy to allow women with uterine factor infertility (UFI) to bear their own children. To date, over 60 UTx have been performed, resulting in 15 live births. Our study investigates the attitudes, perspectives, and interests of women with UFI towards UTx.

METHODS: Anonymous questionnaires were distributed electronically to women diagnosed with UFI at Johns Hopkins Hospital between the years 2003 and 2018.

RESULTS: Thirty-one women with UFI were identified, resulting in 10 completed surveys. The average age was 31.7 ± 6.31 years, and the average age of diagnosis was 20 years (range 14-31); …

Acute Appendicitis Associated With Kawasaki Disease: Case Report And Review Of The Literature, Kaku Kuroda, Morgan Stottlemyre

Open Access Publications

Acute appendicitis is a rare complication of Kawasaki disease in the setting of the absence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We experienced a rare case of acute appendicitis associated with Kawasaki disease. The patient is a six-year-old male who was brought to the emergency department by his mother with a pruritic rash, nausea, vomiting, and abdominal pain. Given fever, tenderness in the right lower quadrant on physical examination, leukocytosis with bandemia, and a non-compressible and dilated appendix on ultrasound, he was diagnosed with acute appendicitis and was treated with a laparoscopic appendectomy. He developed persistent fevers …

Pretreatment Neutrophil-To-Lymphocyte Ratio As An Important Prognostic Marker In Stage Iii Locally Advanced Non-Small Cell Lung Cancer: Confirmatory Results From The Proclaim Phase Iii Clinical Trial, Tithi Biswas, Rohin Gawdi, Charulata Jindal, Sharanya Iyer, Kylie H. Kang, David Bajor, Mitchell Machtay, Yuk Ming Choi, Jimmy T. Efird

Open Access Publications

Background: Neutrophil-to-lymphocyte ratio (NLR) is an important pretreatment marker of systemic inflammation and tumor aggressiveness. Increased levels of this ratio have been associated with reduced survival in several observational studies of lung cancer. However, supporting analyses from large clinical trial data are lacking.

Methods: To validate the prognostic role of NLR, the current study evaluated data from a randomized phase III study (PROCLAIM; clinicaltrial.gov ID: NCT00686959) of patients with stage IIIA/B, unresectable, non-squamous, non-small cell lung cancer (NSCLC), originally comparing combination pemetrexed-cisplatin chemoradiotherapy with etoposide-cisplatin chemoradiotherapy. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for survival were estimated using …

Dicer1 Tumor Predisposition Syndrome: An Evolving Story Initiated With The Pleuropulmonary Blastoma, Iván A González, Douglas R Stewart, Kris Ann P Schultz, Amanda P Field, D Ashley Hill, Louis P Dehner

Open Access Publications

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation …

Genetic Characterization, Current Model Systems And Prognostic Stratification In Pax Fusion-Negative Vs. Pax Fusion-Positive Rhabdomyosarcoma, Carina A Dehner, Amy E Armstrong, Marielle Yohe, Jack F Shern, Angela C Hirbe

Open Access Publications

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status (

Antibiotic-Induced Disturbances Of The Gut Microbiota Result In Accelerated Breast Tumor Growth, Alastair M Mckee, Katherine N Weilbaecher, Et Al

Open Access Publications

The gut microbiota's function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria,

Effectiveness Of Mrna Covid-19 Vaccine Among U.S. Health Care Personnel, Tamara Pilishvili, Jennie H. Kwon, Et Al

Open Access Publications

No abstract provided.

Methodological Rigor And Temporal Trends Of Cardiovascular Medicine Meta-Analyses In Highest-Impact Journals, Dhruv Mahtta, Ahmed Altibi, Mohamed M Gad, Amjad Samara, Amr F Barakat, Rodrigo Bagur, Hend Mansoor, Hani Jneid, Salim S Virani, Mamas A Mamas, Ahmad Masri, Islam Y Elgendy

Open Access Publications

Background Well-conducted meta-analyses are considered to be at the top of the evidence-based hierarchy pyramid, with an expansion of these publications within the cardiovascular research arena. There are limited data evaluating the trends and quality of such publications. The objective of this study was to evaluate the methodological rigor and temporal trends of cardiovascular medicine-related meta-analyses published in the highest impact journals. Methods and Results Using the Medline database, we retrieved cardiovascular medicine-related systematic reviews and meta-analyses published in

Increased Blood Pressure Variability And The Risk Of Probable Dementia Or Mild Cognitive Impairment: A Post Hoc Analysis Of The Sprint Mind Trial, Adam De Havenon, Mohammad Anadani, Shyam Prabhakaran, Ka-Ho Wong, Shadi Yaghi, Natalia Rost

Open Access Publications

Background Increased systolic blood pressure variability (BPV) is associated with stroke, cardiovascular disease, and dementia and mild cognitive impairment. However, prior studies assessing the relationship between BPV and dementia or mild cognitive impairment had infrequent measurement of blood pressure or suboptimal blood pressure control. Methods and Results We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) MIND (Memory and Cognition in Decreased Hypertension) trial. The primary outcome was probable dementia during follow-up. We defined our exposure period, during which blood pressures were collected, as the first 600 days of the trial, and outcomes were ascertained …

Exploring Contextual Factors Influencing The Implementation Of Evidence-Based Care For Hypertension In Rwanda: A Cross-Sectional Study Using The Coach Questionnaire, Ana Baumann, Cole Hooley, Charles Goss, Vincent Mutabazi, Angela Brown, Kenneth Schechtman, Marc Twagirumukiza, Lisa De Las Fuentes, Dominic Reeds, Makeda Williams, Eugene Mutimura, Anna Bergström, Aurore Nishimwe, Cecile Ingabire, Victor Davila-Roman

Open Access Publications

IMPORTANCE: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

OBJECTIVE: To study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool.

DESIGN: A cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training.

SETTING: Three tertiary care hospitals in Rwanda.

PARTICIPANTS: Healthcare professionals (n=223).

PRIMARY OUTCOMES AND MEASURES: The …

Trichomonas Vaginalis Detection In Urogenital Specimens From Symptomatic And Asymptomatic Men And Women By Use Of The Cobas Tv/Mg Test, Barbara Van Der Pol, David Eisenberg, Et Al

Open Access Publications

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas T. vaginalis/Mycoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of …

Real-World Evaluation Of The Impact Of Implementation Of The Virtuo Blood Culture System In A Tertiary Care Hospital, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren

Open Access Publications

The bioMérieux BacT/Alert Virtuo blood culture system used in combination with resin-containing media may enhance the growth of microorganisms. Our objective was to assess the impact of transitioning to the Virtuo system in comparison to the VersaTREK blood culture system at a tertiary care medical center. We retrospectively reviewed all blood cultures performed at a 1,250-bed academic medical center between January and December 2018 (VersaTREK) and January and December 2019 (Virtuo). Blood culture positivity rates and contamination rates were compared before and after Virtuo implementation. Of 101,438 blood cultures performed during the study period, 48,839 (48.1%) were processed preimplementation and …

Clinicians' Perspectives On The Functions Of Communication In Pediatric Oncology, Bryan A. Sisk, Ginny L. Schulz, Erica C. Kaye, Justin N. Baker, Jennifer W. Mack, James M. Dubois

Open Access Publications

No abstract provided.

Autologous And Allogeneic Hematopoietic Cell Transplantation For Diffuse Large B-Cell Lymphoma–Type Richter Syndrome, Alex F. Herrera, Shalini Shenoy, Et Al

Open Access Publications

No abstract provided.

Falls: A Marker Of Preclinical Alzheimer Disease: A Cohort Study Protocol, Rebecca M Bollinger, Audrey Keleman, Regina Thompson, Elizabeth Westerhaus, Anne M Fagan, Tammie Ls Benzinger, Suzanne E Schindler, Chengjie Xiong, David Balota, John C Morris, Beau M Ances, Susan L Stark

Open Access Publications

INTRODUCTION: Progression to symptomatic Alzheimer disease (AD) occurs slowly over a series of preclinical stages. Declining functional mobility may be an early indicator of loss of brain network integration and may lead to an increased risk of experiencing falls. It is unknown whether measures of functional mobility and falls are preclinical markers of AD. The purpose of this study is to examine (1) the relationship between falls and functional mobility with AD biomarkers to determine when falls occur within the temporal progression to symptomatic Alzheimer disease, and (2) the attentional compared with perceptual/motor systems that underlie falls and functional mobility …

Neuropathic Pain: Biomolecular Intervention And Imaging Via Targeting Microglia Activation, Aijun Ji, Jinbin Xu

Open Access Publications

Many diseases, including cancer, can lead to neuropathic pain (NP). NP is one of the accompanying symptoms of suffering in many conditions and the life quality of NP patient is seriously affected. Due to complex causes, the effects of clinical treatments have been very unsatisfactory. Many experts have found that neuron-microglia interaction plays an essential role in NP occurrence and development. Therefore, the activation of microglia, related inflammatory mediators and molecular and cellular signaling pathways have become the focus of NP research. With the help of modern functional imaging technology, advanced pre-and clinical studies have been carried out and NP …

Signaling Through Retinoic Acid Receptors Is Essential For Mammalian Uterine Receptivity And Decidualization, Yan Yin, Meade E. Haller, Sangappa B. Chadchan, Ramakrishna Kommagani, Liang Ma

Open Access Publications

Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. …

Racial Disparities In Modifiable Risk Factors And Statin Usage In Black Patients With Familial Hypercholesterolemia, Anandita Agarwala, Nathan Bekele, Elena Deych, Michael W Rich, Aliza Hussain, Laney K Jones, Amy C Sturm, Karen Aspry, Elizabeth Nowak, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

Open Access Publications

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of …

Brain White Matter Structure And Amyloid Deposition In Black And White Older Adults: The Aric-Pet Study, Keenan A Walker, Noah Silverstein, Yun Zhou, Timothy M Hughes, Clifford R Jack, David S Knopman, A Richey Sharrett, Dean F Wong, Thomas H Mosley, Rebecca F Gottesman

Open Access Publications

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion …

Social Determinants Of Health Discussed With Mothers During Personal Visits Before And During The Covid-19 Pandemic, Rachel G Tabak, Cynthia D Schwarz, Allison Kemner, Shelly Johnston, Adriana Aramburu, Debra Haire-Joshu

Open Access Publications

No abstract provided.

Protection Levels Of N95-Level Respirator Substitutes Proposed During The Covid-19 Pandemic: Safety Concerns And Quantitative Evaluation Procedures, David Ballard, Alex Scott, Broc Burke, Jason Morris, Connie Gan, Jesse Hu, Udayabhanu Jammalamadaka, Sena Sayood, Stephen Liang, Bruno Maranhao, J. Tyler Bertroche, Nirah Shomer, Pamela Woodard, Kathleen Meacham, Et Al

Open Access Publications

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories.

SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies.

PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators.

METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute …

Loss Of Synergistic Transcriptional Feedback Loops Drives Diverse B-Cell Cancers, Jared M Andrews, Sarah C Pyfrom, Jennifer A Schmidt, Olivia I Koues, Rodney A Kowalewski, Nicholas R Grams, Jessica J Sun, Leigh R Berman, Eric J Duncavage, Yi-Shan Lee, Amanda F Cashen, Eugene M Oltz, Jacqueline E Payton

Open Access Publications

BACKGROUND: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping "cell-of-origin". Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry.

METHODS: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using >325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and …

Phagocytes Produce Prostaglandin E2 In Response To Cytosolic Listeria Monocytogenes, Courtney E. Mcdougal, Zachary T. Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M. Stevenson, Daniel Amador-Noguez, Mark J. Miller, John-Demian Sauer

Open Access Publications

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 …

Endothelial Fgf Signaling Is Protective In Hypoxia-Induced Pulmonary Hypertension, Kel Vin Woo, Isabel Y Shen, Carla J Weinheimer, Attila Kovacs, Jessica Nigro, Chieh-Yu Lin, Murali Chakinala, Derek E Byers, David M Ornitz

Open Access Publications

Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH. Mice lacking endothelial FGFR1/2, mice with activated endothelial FGFR signaling, and human pulmonary artery endothelial cells (HPAECs) were challenged with hypoxia. We assessed the effect of FGFR activation and inhibition on right ventricular pressure, vascular remodeling, and endothelial-mesenchymal transition …

A Comparison Of Machine Learning Classifiers For Pediatric Epilepsy Using Resting-State Functional Mri Latency Data, Ryan D Nguyen, Matthew D Smyth, Liang Zhu, Ludovic P Pao, Shannon K Swisher, Emmett H Kennady, Anish Mitra, Rajan P Patel, Jeremy E Lankford, Gretchen Von Allmen, Michael W Watkins, Michael E Funke, Manish N Shah

Open Access Publications

Epilepsy affects 1 in 150 children under the age of 10 and is the most common chronic pediatric neurological condition; poor seizure control can irreversibly disrupt normal brain development. The present study compared the ability of different machine learning algorithms trained with resting-state functional MRI (rfMRI) latency data to detect epilepsy. Preoperative rfMRI and anatomical MRI scans were obtained for 63 patients with epilepsy and 259 healthy controls. The normal distribution of latency z-scores from the epilepsy and healthy control cohorts were analyzed for overlap in 36 seed regions. In these seed regions, overlap between the study cohorts ranged from …

Alterations Of The Gut Mycobiome In Patients With Ms, Saumya Shah, Alberto Locca, Claudia Cantoni, Laura Ghezzi, Emily Evans, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Et Al

Open Access Publications

BACKGROUND: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied.

METHODS: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months.

FINDINGS: The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16 …

Cryptorchidism As An Obscure Cause Of Adhesive Small Bowel Obstruction In An Adult, A Case Report, Savni Satoskar, Sarang Kashyap, Joshua Ziehm, Francisco Benavides, Avian Chang, Vinay Singhal

Open Access Publications

INTRODUCTION AND IMPORTANCE: Cryptorchidism is seen in 3% of fullterm neonates. Rarely, it may cause small bowel obstruction. Knowledge of this presentation of cryptorchidism is essential to treat bowel obstruction arising due to cryptorchidism before the patient suffers complications.

CASE PRESENTATION: We present a case of a patient who underwent exploratory laparotomy for small bowel obstruction that did not resolve with conservative management. At laparotomy, on initial exploration, this patient had adhesive bands causing the small bowel obstruction. On further exploration, the bands were found to arise from a cryptorchid testis.

CLINICAL DISCUSSION: Cryptorchidism is a common finding among newborns …