Medicine and Health Sciences Commons^™

Sksr1 Identified As Key Virulence Factor In Cryptosporidium By Genetic Crossing, Wei He, Lianbei Sun, Tianyi Hou, Zuwei Yang, Fuxian Yang, Shengchen Zhang, Tianpeng Wang, Xinran Wang, Na Li, Yaqiong Guo, L David Sibley, Yaoyu Feng, Lihua Xiao

2020-Current year OA Pubs

Cryptosporidium is a major cause of severe diarrhea. Although Cryptosporidium isolates exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we use classical genetics to cross two Cryptosporidium parvum isolates of different virulence and use bulk segregant analysis of whole-genome sequences from the progeny to identify quantitative trait loci (QTL) associated with Cryptosporidium infectivity and virulence. Of the 23 genes in three QTL, two have loss-of-function mutations in the low-virulence isolates, including the SKSR1 gene encoding a variant secretory protein. Deletion of the SKSR1 gene or expression of the frame-shifted …

Rapamycin Treatment For Alzheimer's Disease And Related Dementias: A Pilot Phase 1 Clinical Trial, Mitzi M Gonzales, Miranda E Orr, Yingxin He, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rapamycin has been shown to extend lifespan and acts on pathologies underlying Alzheimer's disease and related dementias in animal models. However, rapamycin's clinical application remains underexplored.

METHODS: We conducted a single-site open-label phase 1 clinical trial (ClinicalTrials.gov: NCT04200911) to examine the effects of rapamycin in humans. Eligible participants were people 55-85 years old with mild cognitive impairment or early-stage dementia, which was defined as having a Global Clinical Dementia Rating Scale Score of 0.5-1. All participants received rapamycin (1 mg/day) for eight weeks. The primary aim was to evaluate rapamycin's central nervous system penetrance by assaying drug levels in …

Dual-Responsive Synthetic Gene Circuit For Dynamic Biologic Drug Delivery Via Inflammatory And Circadian Signaling Pathways, Amanda Cimino, Fiona Pat, Omolabake Oyebamiji, Christine T N Pham, Erik D Herzog, Farshid Guilak

2020-Current year OA Pubs

BACKGROUND: Engineered cells provide versatile tools for precise, tunable drug delivery, especially when synthetic stimulus-responsive gene circuits are incorporated. In many complex disease conditions, endogenous pathologic signals such as inflammation can vary dynamically over different time scales. For example, in autoimmune conditions such as rheumatoid arthritis or juvenile idiopathic arthritis, local (joint) and systemic inflammatory signals fluctuate daily, peaking in the early morning, but can also persist over long periods of time, triggering flare-ups that can last weeks to months. However, treatment with disease-modifying anti-rheumatic drugs is typically provided at continuous high doses, regardless of disease activity and without consideration …

The Role Of Organizational Characteristics In Intervention Sustainment: Findings From A Quantitative Analysis In 42 Hiv Testing Clinics In Vietnam, Sophia M Bartels, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Evidence-based intervention (EBI) sustainment is one of public health's largest translational research problems. Fewer than half of public health EBIs are sustained long-term, and sustainment challenges are even more pressing in low and middle-income countries (LMICs). Organizational characteristics, including organizations' inner structures, culture, and climate, may play a key role in EBI sustainment. However, little quantitative research has examined these relationships, particularly in LMICs.

METHODS: In this observational study, we assessed the association between baseline organizational characteristics and EBI sustainment within a cluster randomized implementation trial in Vietnam testing strategies to scale-up Systems Navigation and Psychosocial Counseling (SNaP) for …

Psychiatric Genome-Wide Association Study Enrichment Shows Promise For Future Psychopharmaceutical Discoveries, Alexander S Hatoum, Aaron J Gorelik, Lauren Blaydon, Spencer B Huggett, Tingying Chi, David A A Baranger, Alex P Miller, Emma C Johnson, Arpana Agrawal, Ryan Bogdan

2020-Current year OA Pubs

BACKGROUND: Innovation in psychiatric therapeutics has stagnated on known mechanisms. Psychiatric genome-wide association studies (GWAS) have identified hundreds of genome-wide significant (GWS) loci that have rapidly advanced our understanding of disease etiology. However, whether these results can be leveraged to improve clinical treatment for specific psychiatric disorders remains poorly understood.

METHODS: In this proof-of-principal evaluation of GWAS clinical utility, we test whether the targets of drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BiP), Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD), Schizophrenia (SCZ), Substance Use Disorders (SUDs), and insomnia (INS), are enriched …

Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson

WUSM Theses and Dissertations – All Programs

The expansion of intra-muscular adipose tissue (IMAT) between myofibers and epi-muscular adipose tissue (EMAT) outside of the muscle boundary accompanies numerous pathologies including diabetes, muscular dystrophy, and aging. IMAT and EMAT are anatomically juxtaposed to myofibers. Some evidence supports that IMAT and EMAT impede muscle function. This is potentially due to paracrine factors that are secreted by IMAT/EMAT. Different adipose depots can be classified in numerous ways including where they are located anatomically as well as the factors in which they secrete. Unlike classical white fat, adipose depots classified as brown or beige, noted by the marker uncoupling protein-1 (UCP-1) …

Toward An Understanding Of Loneliness And Social Participation In Serious Mental Illness, Samantha B. Randolph

WUSM Theses and Dissertations – All Programs

Loneliness is an immense challenge facing the majority of Americans with Serious Mental Illness. Loneliness is linked to negative outcomes, including heart disease, reduced quality of life, and early mortality. Current loneliness interventions (e.g., social skills training, social support) do not effectively address all the complex factors that lead to loneliness in this population. More work is needed, therefore, to better understand how to optimally research and prevent loneliness among individuals with Serious Mental Illness, who experience unique barriers to social integration/participation and dwell in complex settings, such as permanent supportive housing. The presented dissertation aims to address current gaps …

A Theory-Based Examination Of Factors Influencing Caregivers’ Intentions To Disclose Sickle Cell Trait Status To Their Children, Christine A. Chaba

WUSM Theses and Dissertations – All Programs

Sickle cell trait (SCT), the heterozygous form of sickle cell disease, has significant implications for health and reproductive decision-making. Timely disclosure of SCT status to children by their caregivers is critical for promoting genetic awareness and supporting informed reproductive choices. However, many caregivers delay or avoid this conversation. This study examined the psychosocial and behavioral factors influencing caregivers’ intentions to disclose SCT status to their children, guided by the Theory of Planned Behavior and the Theory of Regret Regulation. A descriptive, cross-sectional study was conducted with 78 caregivers of Children with SCT, who completed an online survey. The study addressed …

Label-Free Multimodal Optical Biopsy Reveals Biomolecular And Morphological Features Of Diabetic Kidney Tissue In 2d And 3d, Anthony A Fung, Zhi Li, Craig Boote, Petar Markov, Joseph P Gaut, Sanjay Jain, Lingyan Shi

2020-Current year OA Pubs

Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities-stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)-within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, …

A Phase I Dose-Escalation Study Of The Hif-2 Alpha Inhibitor Dff332 In Patients With Advanced Clear-Cell Renal Cell Carcinoma, Sumanta K Pal, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Mutations or silencing of the von Hippel-Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in the oncogenesis of ∼50% of patients with clear-cell renal cell carcinoma (ccRCC) but has been considered "undruggable." DFF332, an orally administered novel allosteric inhibitor of HIF-2α, showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

PATIENTS AND METHODS: This first-in-human study evaluated the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of DFF332 in patients with heavily pretreated advanced ccRCC. Preliminary data from the dose escalation of DFF332 monotherapy, administered orally at 50 or 100 mg weekly or 25, 50, 100, or …

Meningeal Lymphatics-Microglia Axis Regulates Synaptic Physiology, Kyungdeok Kim, Daviti Abramishvili, Siling Du, Zachary Papadopoulos, Jay Cao, Jasmin Herz, Igor Smirnov, Jean-Leon Thomas, Marco Colonna, Jonathan Kipnis

2020-Current year OA Pubs

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks. These synaptic and behavioral alterations induced by lymphatic dysfunction are mediated by microglia, leading to increased expression of the interleukin 6 gene (Il6). IL-6 drives inhibitory synapse phenotypes via a combination of trans- and classical IL-6 …

Network Analysis Of The Cerebrospinal Fluid Proteome Reveals Shared And Unique Differences Between Sporadic And Familial Forms Of Amyotrophic Lateral Sclerosis, Adam N Trautwig, Cindy V Ly, Timothy M Miller, Et Al.

2020-Current year OA Pubs

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.

METHODS: We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, …

Modulation Of Her2 Internalization Enhances Single-Dose Antibody-Drug Potency In Her2+ Gastric Cancer, Abbey Zidel, Alex Benton, Emma Brown, Shayla Shmuel, Alex Vanover, Sandeep Surendra Panikar, Ron Bose, Haeseong Park, Andrew A Davis, Patrícia M R Pereira

2020-Current year OA Pubs

HER2 is a membrane receptor tyrosine kinase overexpressed in 18-20% of gastric tumors. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that targets HER2-positive (HER2

Acute Kidney Injury Triggers Hypoxemia By Lung Intravascular Neutrophil Retention That Reduces Capillary Blood Flow, Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J. Miller, Shinichi Kawana, Hailey M Shepherd, Wenjun Li, Daniel Kreisel, Andreas Herrlich

2020-Current year OA Pubs

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induced rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote …

Maintenance Of Graft Tissue-Resident Foxp3+ Cells Is Necessary For Lung Transplant Tolerance In Mice, Wenjun Li, Yuriko Terada, Yun Zhu Bai, Yuhei Yokoyama, Hailey M. Shepherd, Junedh M. Amrute, Amit I. Bery, Zhiyi Liu, Jason M. Gauthier, Marina Terekhova, Jon H. Ritter, Varun Puri, Ramsey R. Hachem, Maxim N. Artyomov, Kory J. Lavine, Ruben G. Nava, Andrew E. Gelman, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these Foxp3+ cells suppress alloimmune responses locally and systemically. Here, we demonstrated that Foxp3+ cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded. Using a mouse lung retransplant model, we showed that recipient Foxp3+ cells were continuously recruited to the BALT within tolerant allografts. We identified distinguishing features of graft-resident and newly recruited Foxp3+ cells and showed that graft-infiltrating Foxp3+ …

Radiation Dosimetry Of [11c]Tz1964b As Determined By Whole-Body Pet Imaging Of Nonhuman Primates, Baijayanta Maiti, Noah L Goldman, Mahdjoub Hamdi, Jason Lenox-Krug, Morvarid Karimi, Stephen M Moerlein, Richard Laforest, Tianyu Huang, Zhude Tu, Joel S Perlmutter, Scott A Norris

2020-Current year OA Pubs

BACKGROUND: Phosphodiesterase 10A (PDE10A) is a postsynaptic, membrane bound cyclic nucleotide phosphodiesterase that is highly enriched in the striatal medium spiny neurons and regulates dopaminergic neurotransmission. The objective of this study is to determine the absorbed radiation dosimetry of a novel radiotracer for PDE10A: 3-(Methoxy-

RESULTS: Highest retention was observed in the liver with total time-integrated activity of ~ 0.23 h. Absorbed organ dosimetry was highest in the liver (53.3 μGy/MBq), making it the critical organ. Gallbladder (35.9 μGy/MBq) and spleen (35.4 μGy/MBq) were the next highest organs for absorbed radiation dose. Effective doses were estimated to be 5.02 and …

Autophagy Is Required For The Therapeutic Effects Of The Nad+ Precursor Nicotinamide In Obesity-Related Heart Failure With Preserved Ejection Fraction, Mahmoud Abdellatif, Moydul Islam, Abhinav Diwan, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Role For Δ Subunit-Containing Gabaa Receptors On Parvalbumin-Positive Neurons In Maintaining Electrocortical Signatures Of Sleep States, Peter M Lambert, Sofia V Salvatore, Xinguo Lu, Hong-Jin Shu, Ann Benz, Nicholas Rensing, Carla M Yuede, Michael Wong, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

GABA

Comparison Of Broad-Spectrum Anti-Pseudomonal Beta-Lactam Antibiotics Versus Targeted Therapy For Neutropenic Patients With Methicillin-Susceptible, Lauren C Russell, Jeff Klaus, Miguel A Chavez, Erik R Dubberke, Tamara Krekel

2020-Current year OA Pubs

The safety of the utilization of methicillin-susceptible

Novel Treatment Approaches Utilizing Antibody-Drug Conjugates In Breast Cancer, Andrew A Davis, Jennifer Hesse, Patrícia M R Pereira, Cynthia X Ma

2020-Current year OA Pubs

Antibody-drug conjugates (ADCs) are rapidly changing the way we treat patients with breast cancer. Despite this progress, many unanswered questions remain regarding the sequencing of different ADCs with similar payloads, optimal combinations, drug design strategies to limit off-target toxicities, biomarkers to define antigen positivity, and the use of ADCs in the neoadjuvant and adjuvant settings. In this review, we summarize novel ADC approaches in breast cancer treatment, including potential improvements in ADC payloads, linkers, targets, and drug delivery. We also evaluate novel strategies to combine ADCs with other agents, such as targeted drugs and immune checkpoint inhibitors. To improve patient …

When The Parts Are Greater Than The Whole: How Understanding Mechanisms Can Advance Implementation Research, Elvin H Geng, Byron J Powell, Charles W Goss, Cara C Lewis, Anne E Sales, Bo Kim

2020-Current year OA Pubs

BACKGROUND: Does the importance of context in implementation imply that generalizing about the effects of strategies is ultimately limited? Conceptual approaches for generalizing in the presence of significant contextual heterogeneity could advance implementation research but require novel perspectives.

MAIN BODY: Drawing from perspectives from Realist approaches, Pearl's transportability framework and philosophy of science, this paper outlines a mechanism-based approach to generalizing about the effects of implementation strategies. We suggest that understanding mechanisms creates a conceptual bridge between the effects of a strategy and the influence of the implementation context. Using directed acyclic graphs to represent the mechanisms of strategies, we …

Soft, Skin-Interfaced Wireless Electrogoniometry Systems For Continuous Monitoring Of Finger And Wrist Joints, Hee-Sup Shin, Jihye Kim, Nicholas Fadell, Logan B Pewitt, Yusuf Shaaban, Claire Liu, Min-Seung Jo, Josif Bozovic, Andreas Tzavelis, Minsu Park, Kelly Koogler, Jin-Tae Kim, Jae-Young Yoo, John A Rogers, Mitchell A Pet

2020-Current year OA Pubs

Continuous kinematic biofeedback during exercise interventions can lead to improved therapeutic outcomes in hand and wrist rehabilitation. Conventional methods for measuring joint kinematics typically allow only static measurements performed by specially trained therapists. This paper introduces skin-conformal, wearable wireless systems designed to continuously and accurately capture the angles of target joints, specifically in hand and wrist. Supported by a computer vision-based calibration protocol run on a smart device, these magnetometer-based standalone systems provide patients and clinicians with continuous, real-time data on joint angles and ranges of motion through an intuitive graphical interface. Human trials in healthy volunteers demonstrate the accuracy …

Genome-Wide Analyses Identify 30 Loci Associated With Obsessive-Compulsive Disorder, Nora I. Strom, Arpana Agrawal, Kathleen K. Bucholz, Et Al.

2020-Current year OA Pubs

No abstract provided.

White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space …

Augmented Reality Microscopy To Bridge Trust Between Ai And Pathologists, Sunil Badve, Xiuli Liu, Et Al.

2020-Current year OA Pubs

Diagnostic certainty is the cornerstone of modern medicine and critical for maximal treatment benefit. When evaluating biomarker expression by immunohistochemistry (IHC), however, pathologists are hindered by complex scoring methodologies, unique positivity cut-offs and subjective staining interpretation. Artificial intelligence (AI) can potentially eliminate diagnostic uncertainty, especially when AI "trustworthiness" is proven by expert pathologists in the context of real-world clinical practice. Building on an IHC foundation model, we employed pathologists-in-the-loop finetuning to produce a programmed cell death ligand 1 (PD-L1) CPS AI Model. We devised a multi-head augmented reality microscope (ARM) system overlayed with the PD-L1 CPS AI Model to assess …

Phase Ii Study Of Venetoclax Added To Bendamustine And Obinutuzumab In Patients With High-Risk Follicular Lymphoma As Front-Line Therapy: Pre0403, Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl

2020-Current year OA Pubs

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate …

A Scoping Review Of Remote And Unsupervised Digital Cognitive Assessments In Preclinical Alzheimer's Disease, Sarah E Polk, Fredrik Öhman, Jason Hassenstab, Alexandra König, Kathryn V Papp, Michael Schöll, David Berron

2020-Current year OA Pubs

Characterizing subtle cognitive changes in preclinical Alzheimer's disease (AD) is difficult using traditional neuropsychological assessments. Remote and unsupervised digital assessments can improve scalability, measurement reliability, and ecological validity, enabling the capture of subtle changes. We evaluate such tools for use in preclinical AD, or cognitively unimpaired individuals with abnormal levels of AD pathology. We screened 1904 reports for studies remotely assessing cognition in preclinical AD samples. Twenty-three tools were identified, and their usability, reliability, and validity, including construct and criterion validity based on in-person neuropsychological and Aβ/tau measures, was reported. We present a necessary update to a rapidly evolving field, …

Optimizing Peptide Nucleic Acid-Based Pretargeting For Enhanced Targeted Radionuclide Therapy, Mohamed Altai, Ábel Nagy, Pauline Granit, Wahed Zedan, Myriam Cerezo-Magaña, Julie Park, Katharina Lückerath, Susanne Geres, Marie Sydoff, Daniel L J Thorek, Kristina Westerlund, David Ulmert, Amelie Eriksson Karlström

2020-Current year OA Pubs

Radiolabeled targeting agents have emerged as valuable tools for the treatment of disseminated cancer. Monoclonal antibodies (mAbs) are widely employed as carriers for diagnostic and therapeutic radionuclides due to their exceptional specificity and affinity. However, their prolonged circulatory half-life can diminish diagnostic efficacy and increase radiation exposure to non-target tissues in therapeutic applications, resulting in dose-limiting toxicities. To overcome this limitation, pretargeting technologies emerge as promising strategies to enhance tumor-to-background ratio and reduce radiation exposure of healthy tissues. Our previous work introduced a pretargeting concept leveraging the specific interaction between two peptide nucleic acid (PNA) probes, HP1 and HP2, as …

Molecular Basis Of Trpv3 Channel Blockade By Intracellular Polyamines, Jingying Zhang, Peng Yuan, Colin G Nichols, Grigory Maksaev

2020-Current year OA Pubs

ThermoTRPV1-4 channels are involved in the regulation of multiple physiological processes, including thermo- and pain perception, thermoregulation, itch, and nociception and therefore tight control of their activity is a critical requirement for correct perception of noxious stimuli and pain. We previously reported a voltage-dependent inhibition of TRPV1-4 channels by intracellular polyamines that could be explained by high affinity spermine binding in, and passage through, the permeation path. Here, using electrophysiology and cryo-electron microscopy, we elucidate molecular details of TRPV3 blockade by endogenous spermine and its analog NASPM. We identify a high-affinity polyamine interaction site at the intracellular side of the …

Recombinant Interleukin-7 Treatment Of Refractory Refractory Mycobacterium Avium Complexlung Disease (Impulse-7): A Pilot Phase Ii, Single-Center, Randomized, Clinical Trial, Carlos Mejia-Chew, Andrej Spec, Andrew H Walton, Alina Ulezko Antonova, Alexandra Dram, Sanjeev Bhalla, Marco Colonna, Michel Morre, Richard Hotchkiss

2020-Current year OA Pubs

BACKGROUND: Nontuberculous mycobacteria disease is an emerging opportunistic infection that is often refractory to therapy. Interleukin 7 (IL-7) is a pleiotropic cytokine with broad-ranging effects that enhance immunity and augment monocyte/macrophage anti-

OBJECTIVES: This study evaluated IL-7 in patients with refractory

DESIGN: Prospective, single-center, randomized, study of IL-7 in patients with refractory MAC-LD.

METHODS: Randomization (two sets of 4 weekly IL-7 injections) was stratified based on the presence of pulmonary cavities. The primary outcome was sputum culture conversion to negative within 6 months. Exploratory outcomes included investigation of potential molecular mechanisms of immunosuppression via single-cell RNA sequencing (scRNA-seq).

RESULTS: Of …