Medical Specialties Commons^™

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

Design, Development, And Testing Of Best4baby, An Mhealth Technology To Support Exclusive Breastfeeding In India: Pilot Study., Tony Ma, Katie Chang, Amal Alyusuf, Elina Bajracharya, Yukiko Washio, Patricia J Kelly, Roopa M Bellad, Niranjana S Mahantashetti, Umesh Charantimath, Vanessa Short, Parth Lalakia, Frances J. Jaeger, Shivaprasad Goudar, Richard Derman

Department of Pediatrics Faculty Papers

Background: Exclusive breastfeeding (EBF) at 6 months of age in most low- and middle-income countries, including India, is surprisingly low. There is a relative lack of mobile health apps that specifically focus on leveraging the use of peer counselors (PCs) to support mothers as a means of increasing EBF practices in low- and middle-income countries.

Objective: This study aimed to design, develop, and test the usability of Breastfeeding Education Support Tool for Baby (BEST4Baby), a mobile health app specifically designed to support PCs in providing in-home breastfeeding counseling support to mothers in rural India on optimal breastfeeding practices.

Methods: A …

Retroperitoneal Ancient Neurilemmoma: A Nervous Rarity., Vaidehi Mendpara, Sweta Sahu, Devarsh N. Shaw, Subhangi Parmar, Tanveer Ahamad Shaik, Swastika Sadhai, Mukesh Pancholi

Faculty and Staff Scholarship

Neurilemmomas are tumors of neural origin that comprise Schwann cell proliferation in a characteristic pattern. They are benign in nature. Ancient neurilemmomas are usually longstanding growths that exhibit degenerative features that could be mistaken for malignancy. We report a case of ancient neurilemmoma in a 70-year-old male patient in the retroperitoneal area. Retroperitoneal schwannomas are extremely uncommon along with ancient neurilemmoma features making it worth reporting

Modelling Aggressive Prostate Cancers Of Young Men In Immune-Competent Mice, Driven By Isogenic Trp53 Alterations And Pten Loss, Javier Octavio Mejía-Hernández, Simon P Keam, Reem Saleh, Fenella Muntz, Stephen B Fox, David Byrne, Arielle Kogan, Lokman Pang, Jennifer Huynh, Cassandra Litchfield, Franco Caramia, Guillermina Lozano, Hua He, James M You, Shahneen Sandhu, Scott G Williams, Ygal Haupt, Sue Haupt

Faculty, Staff and Student Publications

Understanding prostate cancer onset and progression in order to rationally treat this disease has been critically limited by a dire lack of relevant pre-clinical animal models. We have generated a set of genetically engineered mice that mimic human prostate cancer, initiated from the gland epithelia. We chose driver gene mutations that are specifically relevant to cancers of young men, where aggressive disease poses accentuated survival risks. An outstanding advantage of our models are their intact repertoires of immune cells. These mice provide invaluable insight into the importance of immune responses in prostate cancer and offer scope for studying treatments, including …

September 2022: Region 10 Emerging Special Pathogen Treatment Center (Resptc) At Providence Sacred Heart Medical Center & Children’S Hospital, Providence - Special Pathogens Program

Special Pathogens Newsletters

REGION 10 SPECIAL PATHOGENS NEWSLETTER

Protecting Wellness And Boundaries While Navigating Leaves Of Absences: Case Studies For Approaching From An Ethical And Behavioral Health Lens, Jennifer Kowalkowski, Sawsan Edriss, Stephen Warnick

Website/Multimedia Contributions

The new ACGME guidelines for paid 6-week family and medical leave are a big step forward in helping our residents maintain their health and well-being. Previously noted for having one of the strictest leave allowances among medical specialties, family medicine programs may see future increases in leave requests due to policy changes extending allowable leave times and increased stress from both the Covid-19 pandemic and current mental health crisis facing our nation. Leaves that involve physical or mental health crises are certainly very difficult for the resident on leave but can significantly impact co-residents and program faculty as well. Our …

Transplantation Of Astrocytic Mitochondria Modulates Neuronal Antioxidant Defense And Neuroplasticity And Promotes Functional Recovery After Intracerebral Hemorrhage, Ryosuke Tashiro, Jesus Bautista-Garrido, Dan Ozaki, Guanghua Sun, Lidiya Obertas, Alexis S Mobley, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung

Faculty, Staff and Student Publications

Astrocytes release functional mitochondria (Mt) that play regulatory and prosurvival functions on entering adjacent cells. We recently demonstrated that these released Mts could enter microglia to promote their reparative/prophagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, the relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt, which …

Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao

School of Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or …

Smart-Home Concept For Remote Monitoring Of Instrumental Activities Of Daily Living (Iadl) In Older Adults With Cognitive Impairment: A Proof Of Concept And Feasibility Study, Myeounggon Lee, Ram Kinker Mishra, Anmol Momin, Nesreen El-Refaei, Amir Behzad Bagheri, Michele K York, Mark E Kunik, Marc Derhammer, Borna Fatehi, James Lim, Rylee Cole, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Assessment of instrumental activities of daily living (IADL) is essential for the diagnosis and staging of dementia. However, current IADL assessments are subjective and cannot be administered remotely. We proposed a smart-home design, called IADLSys, for remote monitoring of IADL. IADLSys consists of three major components: (1) wireless physical tags (pTAG) attached to objects of interest, (2) a pendant-sensor to monitor physical activities and detect interaction with pTAGs, and (3) an interactive tablet as a gateway to transfer data to a secured cloud. Four studies, including an exploratory clinical study with five older adults with clinically confirmed cognitive impairment, who …

Why Study Mechanisms Of Brain Stimulation Therapies? To Modulate The Right Neurons, In The Right Way, At The Right Time, Matthew J Mcginley, Steven T Lee

Duncan NRI Faculty and Staff Publications

Clinical applications of vagus nerve stimulation (VNS) are burgeoning, but mechanistic work lags behind. In this issue of Neuron, Bowles and colleagues show that VNS timed with positive reinforcement improves motor learning and cortical function by a cholinergic mechanism.

Fighting For Recovery On Multiple Fronts: The Past, Present, And Future Of Clinical Trials For Spinal Cord Injury, Valerie A Dietz, Nolan Roberts, Katelyn Knox, Sherilynne Moore, Michael Pitonak, Chris Barr, Jesus Centeno, Scott Leininger, Kent C New, Peter Nowell, Matthew Rodreick, Cedric G Geoffroy, Argyrios Stampas, Jennifer N Dulin

Faculty, Staff and Student Publications

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of …

Review: Management Of Midshaft Clavicle Fractures In Adolescents , Matthew B. Holloway

Longitudinal Scholar's Project

Clavicle fractures are common injuries that occur across all age ranges, but are largely seen in young, active males. The majority of these fractures (70-80%) occur in the midshaft of the clavicle. The purpose of this review was to compare non-operative treatment to operative treatment of midclavicular fractures and determine whether treatment for adolescent clavicle fractures more closely aligns with pediatric or adult management. Adolescent clavicle fractures are increasingly treated with open reduction and internal fixation, especially in the 15 to 19 age group. Nevertheless, there remains a lack of high-level studies comparing outcomes of operative and conservative treatment specifically …

Symptom Phenotypes In Pulmonary Arterial Hypertension: The Pah “Symptome”, Lee Ann Matura, Jamison D. Fargo, Kathleen Boyle, Jason S. Fritz, Kerri A. Smith, Jeremy A. Mazurek, Diane Pinder, Christine L. Archer-Chicko, Harold I. Palevsky, Allan I. Pack, Marilyn S. Sommers, Steven M. Kawut

Abington Jefferson Health Papers

Women with pulmonary arterial hypertension (PAH) experience multiple symptoms, including dyspnea, fatigue, and sleep disturbance, that impair their health‐related quality of life (HRQOL). However, we know little about phenotypic subgroups of patients with PAH with similar, concurrent, multiple symptoms. The objectives of this study were to define the “symptome” by symptom cluster phenotypes and compare characteristics such as biomarkers, cardiac structure and function (echocardiography), functional capacity (6‐min walk distance), and HRQOL between the groups. This cross‐sectional study included 60 women with PAH. Subjects completed an assessment battery: Pulmonary Arterial Hypertension Symptom Scale, Pittsburgh Sleep Quality Index, Multidimensional Dyspnea Profile, Patient‐Reported …

Microrna Expression Levels Change In Neonatal Patients During And After Exposure To Cardiopulmonary Bypass., Lance Hsieh, Lan N. Tu, Alison Paquette, Quanhu Sheng, Shilin Zhao, Douglas C. Bittel, James O'Brien, Kasey Vickers, Peter Pastuszko, Vishal Nigam

Manuscripts, Articles, Book Chapters and Other Papers

Background The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells. Methods and Results We performed miRNA-sequencing on leukocytes isolated from neonatal patients with CPB (n=5) at 7 time points during the process of CPB, …

An Enzymatically Cleavable Tripeptide Linker For Maximizing The Therapeutic Index Of Antibody-Drug Conjugates, Summer Y Y Ha, Yasuaki Anami, Chisato M Yamazaki, Wei Xiong, Candice M Haase, Scott D Olson, Jangsoon Lee, Naoto T Ueno, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama

Faculty, Staff and Student Publications

Valine-citrulline is a protease-cleavable linker commonly used in many drug delivery systems, including antibody-drug conjugates (ADC) for cancer therapy. However, its suboptimal in vivo stability can cause various adverse effects such as neutropenia and hepatotoxicity, leading to dose delays or treatment discontinuation. Here, we report that glutamic acid-glycine-citrulline (EGCit) linkers have the potential to solve this clinical issue without compromising the ability of traceless drug release and ADC therapeutic efficacy. We demonstrate that our EGCit ADC resists neutrophil protease-mediated degradation and spares differentiating human neutrophils. Notably, our anti-HER2 ADC shows almost no sign of blood and liver toxicity in healthy …

The Lawnmower And The Pediatric Lower Extremity: A Catastrophic Combination, Alvaro Tamayo-Gutierrez, Hassan N Ibrahim

Faculty, Staff and Student Publications

Heart failure can lead to renal impairment, an interaction now termed "cardiorenal syndrome." The prevalent physiological explanation for the renal impairment that accompanies heart failure centers around the forward failure hypothesis, which emphasizes the role of left ventricular dysfunction in causing edema, and the backward failure hypothesis, which singles out venous congestion as the dominant mechanism of edema and reduced glomerular filtration rate. In this review, we provide an appraisal on venous congestion, an extremely important contributor that has received little attention. We also summarize the pharmacology of loop diuretics, explain current understanding of diuretic resistance, and address controversies regarding …

Hypertension Management In Patients With Chronic Kidney Disease, Sean A Hebert, Hassan N Ibrahim

Faculty, Staff and Student Publications

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.

Longitudinal Effects Of Combination Antiretroviral Therapy On Cognition And Neuroimaging Biomarkers In Treatment-Naive People With Hiv, Miriam T Weber, Alan Finkelstein, Md Nasir Uddin, Elizabeth Asiago Reddy, Roberto C Arduino, Lu Wang, Madalina E Tivarus, Jianhui Zhong, Xing Qiu, Giovanni Schifitto

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated.

METHODS: We recruited 3 groups of participants from the University …

Clonal Hematopoiesis Is Associated With Increased Risk Of Severe Neurotoxicity In Axicabtagene Ciloleucel Therapy Of Large B-Cell Lymphoma, Neeraj Y Saini, David M Swoboda, Uri Greenbaum, Junsheng Ma, Romil D Patel, Kartik Devashish, Kaberi Das, Mark R Tanner, Paolo Strati, Ranjit Nair, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan P Iyer, Raphael Steiner, Nitin Jain, Loretta Nastoupil, Sanam Loghavi, Guilin Tang, Roland L Bassett, Preetesh Jain, Michael Wang, Jason R Westin, Michael R Green, David A Sallman, Eric Padron, Marco L Davila, Frederick L Locke, Richard E Champlin, Guillermo Garcia-Manero, Elizabeth J Shpall, Partow Kebriaei, Christopher R Flowers, Michael D Jain, Feng Wang, Andrew P Futreal, Nancy Gillis, Sattva S Neelapu, Koichi Takahashi

Faculty, Staff and Student Publications

To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P = 0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade …

A Novel Qkd Approach To Enhance Iiot Privacy And Computational Knacks, Kranthi Kumar Singamaneni, Gaurav Dhiman, Sapna Juneja, Ghulam Muhammad, Salman A Alqahtani, John Zaki

Faculty, Staff and Student Publications

The industry-based internet of things (IIoT) describes how IIoT devices enhance and extend their capabilities for production amenities, security, and efficacy. IIoT establishes an enterprise-to-enterprise setup that means industries have several factories and manufacturing units that are dependent on other sectors for their services and products. In this context, individual industries need to share their information with other external sectors in a shared environment which may not be secure. The capability to examine and inspect such large-scale information and perform analytical protection over the large volumes of personal and organizational information demands authentication and confidentiality so that the total data …

Genetic- And Diet-Induced Ω-3 Fatty Acid Enrichment Enhances Trpv4-Mediated Vasodilation In Mice, Rebeca Caires, Tessa A C Garrud, Luis O Romero, Carlos Fernández-Peña, Valeria Vásquez, Jonathan H Jaggar, Julio F Cordero-Morales

Faculty, Staff and Student Publications

TRPV4 channel activation in endothelial cells leads to vasodilation, while impairment of TRPV4 activity is implicated in vascular dysfunction. Strategies that increase TRPV4 activity could enhance vasodilation and ameliorate vascular disorders. Here, we show that supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid known to have beneficial cardiovascular effects, increases TRPV4 activity in human endothelial cells of various vascular beds. Mice carrying the C. elegans FAT-1 enzyme, which converts ω-6 to ω-3 polyunsaturated fatty acids, display higher EPA content and increased TRPV4-mediated vasodilation in mesenteric arteries. Likewise, mice fed an EPA-enriched diet exhibit enhanced and prolonged TRPV4-dependent vasodilation …

Follicular Lymphoma Microenvironment Characteristics Associated With Tumor Cell Mutations And Mhc Class Ii Expression, Guangchun Han, Qing Deng, Mario L Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J Nomie, Alexander Bagaev, Edwin R Parra, Luisa M Solis Soto, Simrit Parmar, Fredrick B Hagemeister, Sairah Ahmed, Swaminathan P Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H Fowler, Christopher R Flowers, Paolo Strati, Jason R Westin, Sattva S Neelapu, Loretta J Nastoupil, Francisco Vega, Linghua Wang, Michael R Green

Faculty, Staff and Student Publications

Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with …

Ablating Lgr5-Expressing Prostatic Stromal Cells Activates The Erk-Mediated Mechanosensory Signaling And Disrupts Prostate Tissue Homeostasis, Xing Wei, Li Zhang, Yiqun Zhang, Cody Cooper, Chris Brewer, Chia-Feng Tsai, Yi-Ting Wang, Micah Glaz, Hunter B Wessells, Jianwen Que, Mark A Titus, Vincenzino Cirulli, Adam Glaser, Tao Liu, Nicholas P Reder, Chad J Creighton, Li Xin

Faculty, Staff and Student Publications

Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5

Multiseptate Gallbladder Presenting With Biliary Colic., Peter Hopmann, Ellen Tan, David Lo

Surgery Articles

Common diagnoses associated with right upper quadrant and epigastric pain include cholecystitis, peptic ulcer disease (PUD), biliary colic, gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). Multiseptate gallbladder is a rare congenital anomaly that can cause symptoms of biliary colic, however it may present with atypical symptoms, which can prolong definitive diagnosis and treatment. We present a case of multiseptate gallbladder in a 21-year-old female who initially presented with GERD and IBS. After multiple failed treatment regimens for IBS, she ultimately was found to have multiseptate gallbladder and was successfully treated with cholecystectomy.

Frequency Of Bystander Exposure To Antibiotics For Enteropathogenic Bacteria Among Young Children In Low-Resource Settings, Elizabeth T. Rogawski Mcquade, Stephanie A. Brennhofer, Sarah E. Elwood, Timothy L. Mcmurry, Joseph A. Lewnard, Estomih R. Mduma, Sanjaya Shrestha, Najeeha Talat Iqbal, Pascal O. Bessong, Gagandeep Kang

Department of Paediatrics and Child Health

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in …

In Vivo Measurement Of Intradiscal Pressure Changes Related To Thrust And Non-Thrust Spinal Manipulation In An Animal Model: A Pilot Study, William R Reed, Michael A K Liebschner, Carla R Lima, Harshvardhan Singh, Christopher P Hurt, Daniel F Martins, James M Cox, Maruti R Gudavalli

Faculty, Staff and Students Publications

BACKGROUND: The intervertebral disc is a known back pain generator and is frequently the focus of spinal manipulative therapy evaluation and treatment. The majority of our current knowledge regarding intradiscal pressure (IDP) changes related to spinal manual therapy involves cadaveric studies with their inherent limitations. Additional in vivo animal models are needed to investigate intervertebral disc physiological and molecular mechanisms related to spinal manipulation and spinal mobilization treatment for low back disorders.

METHODS: Miniature pressure catheters (Millar SPR-1000) were inserted into either the L4-L5 or L5-L6 intervertebral disc of 3 deeply anesthetized adult cats (Oct 2012-May 2013). Changes in IDP …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Gut Permeability May Be Associated With Periprosthetic Joint Infection After Total Hip And Knee Arthroplasty, Emanuele Chisari, Jeongeun Cho, Marjan Wouthuyzen-Bakker, Javad Parvizi

Rothman Institute Papers

A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system function and ultimately affecting the outcome of interventions. We hypothesized that the loss of mucosal barrier in the gut may be associatedto acute and chronic periprosthetic joint infections (PJI). Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) were tested in plasma as part of …

Recurrent Giant Cell Myocarditis After Heart Transplant: A Case Report, Eitan S. Frankel, Alexander G. Hajduczok, Indranee N. Rajapreyar, Yevgeniy Brailovsky

Division of Cardiology Faculty Papers

BACKGROUND: Giant cell myocarditis (GCM) is a rare but well-known cause of fulminant myocarditis. Despite optimal medical therapy, many patients progress to orthotopic heart transplant (OHT). We present a case of recurrent GCM following OHT, including complex considerations in patient management and infectious sequelae.

CASE SUMMARY: A 33-year-old previously healthy male presented with 2 months of worsening shortness of breath. Transthoracic echocardiogram (TTE) demonstrated a left ventricular ejection fraction of 30-35%. After ruling out an ischaemic aetiology, he was discharged on guideline-directed medical therapy and later presented with productive cough, worsening dyspnoea on exertion, and diarrhoea. He was found to …

Comparative Analysis Of Co-Cultured Amniotic Cell-Conditioned Media With Cell-Free Amniotic Fluid Reveals Differential Effects On Epithelial-Mesenchymal Transition And Myofibroblast Activation, Naiyou Liu, Charles M Bowen, Mohammadali M Shoja, Karen Larissa Castro De Pereira, Laxmi Priya Dongur, Antonio Saad, William K Russell, Thomas Christopher Broderick, Jeffrey H Fair, William Samuel Fagg

Faculty, Staff and Student Publications

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we …