Medicine and Health Sciences Commons^™

Is Local Review Of Positron Emission Tomography Scans Sufficient In Diffuse Large B-Cell Lymphoma Clinical Trials? A Calgb 50303 Analysis, Pallawi Torka, Levi D Pederson, Michael V Knopp, David Poon, Jun Zhang, Brad S Kahl, Howard R Higley, Gary Kelloff, Jonathan W Friedberg, Lawrence H Schwartz, Wyndham H Wilson, John P Leonard, Nancy L Bartlett, Heiko Schöder, Amy S Ruppert

2020-Current year OA Pubs

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS).

METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local …

Baseline Characteristics Of The North American Prodromal Synucleinopathy Cohort, Jonathan E Elliott, Jennifer Mcleland, Susan R Criswell, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were …

Race And Socioeconomic Status Interact With Hpv To Influence Survival Disparities In Oropharyngeal Squamous Cell Carcinoma, Emily Z Yan, Benjamin M Wahle, Sean T Massa, Paul Zolkind, Randal C Paniello, Patrik Pipkorn, Ryan S Jackson, Jason T Rich, Sidharth V Puram, Angela L Mazul

2020-Current year OA Pubs

BACKGROUND: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable prognosis, yet patients of color and low socioeconomic status (SES) continue to experience inferior outcomes. We aim to understand how the emergence of HPV has impacted race and SES survival disparities in OPSCC.

METHODS: A retrospective cohort of 18,362 OPSCC cases from 2010 to 2017 was assembled using the SEER (Surveillance, Epidemiology, and End Results) database. Cox proportional regression and Fine and Gray regression models were used to calculate hazard ratios (HRs) adjusting for race, SES, age, subsite, stage, and treatment.

RESULTS: Black patients had lower overall survival …

Complete Remission Of Widely Metastatic Human Epidermal Growth Factor Receptor 2-Amplified Pancreatic Adenocarcinoma After Precision Immune And Targeted Therapy With Description Of Sequencing And Organoid Correlates, Daniel A King, S Peter Goedegebuure, Xiuli Zhang, Jasreet Hundal, Malachi Griffith, William E Gillanders, Haeseong Park, Et Al.

2020-Current year OA Pubs

No abstract provided.

Persistent Molecular Disease In Adult Patients With Aml Evaluated With Whole-Exome And Targeted Error-Corrected Dna Sequencing, Michael J Slade, Reza Ghasemi, Michelle O'Laughlin, Tasha Burton, Robert S Fulton, Haley J Abel, Eric J Duncavage, Timothy J Ley, Meagan A Jacoby, David H Spencer

2020-Current year OA Pubs

PURPOSE: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML.

MATERIALS AND METHODS: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy. Tumor/normal WES was performed for all patients at presentation. PMD analysis was evaluated in bone marrow samples obtained during clinicopathologic remission using repeat WES and analysis of patient-specific mutations and error-corrected sequencing of 40 recurrently mutated AML genes …

Impact Of The Covid-19 Pandemic On Chronic Disease Management And Patient Reported Outcomes In Patients With Pulmonary Hypertension: The Pulmonary Hypertension Association Registry, Megan Mayer, Murali M Chakinala, Et Al.

2020-Current year OA Pubs

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients …

Regulation Of Astrocyte Lipid Metabolism And Apoe Secretion By The Microglial Oxysterol, 25-Hydroxycholesterol, Anil G Cashikar, Danira Toral-Rios, David Timm, Johnathan Romero, Michael Strickland, Justin M Long, Xianlin Han, David M Holtzman, Steven M Paul

2020-Current year OA Pubs

Neuroinflammation, a major hallmark of Alzheimer's disease and several other neurological and psychiatric disorders, is often associated with dysregulated cholesterol metabolism. Relative to homeostatic microglia, activated microglia express higher levels of Ch25h, an enzyme that hydroxylates cholesterol to produce 25-hydroxycholesterol (25HC). 25HC is an oxysterol with interesting immune roles stemming from its ability to regulate cholesterol metabolism. Since astrocytes synthesize cholesterol in the brain and transport it to other cells via ApoE-containing lipoproteins, we hypothesized that secreted 25HC from microglia may influence lipid metabolism as well as extracellular ApoE derived from astrocytes. Here, we show that astrocytes take up externally …

Expanding The Muscle Imaging Spectrum In Dysferlinopathy: Description Of An Outlier Population From The Classical Mri Pattern, Laura Llansó, Alan Pestronk, Et Al.

2020-Current year OA Pubs

Dysferlinopathy is a muscle disease characterized by a variable clinical presentation and is caused by mutations in the DYSF gene. The Jain Clinical Outcome Study for Dysferlinopathy (COS) followed the largest cohort of patients (n=187) with genetically confirmed dysferlinopathy throughout a three-year natural history study, in which the patients underwent muscle function tests and muscle magnetic resonance imaging (MRI). We previously described the pattern of muscle pathology in this population and established a series of imaging criteria for diagnosis. In this paper, we describe the muscle imaging and clinical features of a subgroup of COS participants whose muscle imaging results …

Extraction Of Clinical Phenotypes For Alzheimer's Disease Dementia From Clinical Notes Using Natural Language Processing, Inez Y Oh, Suzanne E Schindler, Nupur Ghoshal, Albert M Lai, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

OBJECTIVES: There is much interest in utilizing clinical data for developing prediction models for Alzheimer's disease (AD) risk, progression, and outcomes. Existing studies have mostly utilized curated research registries, image analysis, and structured electronic health record (EHR) data. However, much critical information resides in relatively inaccessible unstructured clinical notes within the EHR.

MATERIALS AND METHODS: We developed a natural language processing (NLP)-based pipeline to extract AD-related clinical phenotypes, documenting strategies for success and assessing the utility of mining unstructured clinical notes. We evaluated the pipeline against gold-standard manual annotations performed by 2 clinical dementia experts for AD-related clinical phenotypes including …

Corticosteroids Increase The Risk Of Invasive Fungal Infections More Than Tumor Necrosis Factor-Alpha Inhibitors In Patients With Inflammatory Bowel Disease, Martin H Gregory, Andrej Spec, Dustin Stwalley, Anas Gremida, Carlos Mejia-Chew, Katelin B Nickel, Matthew A Ciorba, Richard P Rood, Margaret A Olsen, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Invasive fungal infections are a devastating complication of inflammatory bowel disease (IBD) treatment. We aimed to determine the incidence of fungal infections in IBD patients and examine the risk with tumor necrosis factor-alpha inhibitors (anti-TNF) compared with corticosteroids.

METHODS: In a retrospective cohort study using the IBM MarketScan Commercial Database we identified US patients with IBD and at least 6 months enrollment from 2006 to 2018. The primary outcome was a composite of invasive fungal infections, identified by ICD-9/10-CM codes plus antifungal treatment. Tuberculosis (TB) infections were a secondary outcome, with infections presented as cases/100 000 person-years (PY). A …

Failure Of Early Mycological Clearance In Hiv-Negative Cryptococcal Meningitis, Zhihui Su, Chongliang Luo, Kai Dai, Dasen Yuan, Bang-E Qin, Meifeng Gu, Junyu Liu, Yong Chen, Fuhua Peng, Ying Jiang

2020-Current year OA Pubs

BACKGROUND: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood.

METHODS: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for

RESULTS: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log

CONCLUSIONS: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy …

Using Synthetic Mr Images For Distortion Correction, David F Montez, Andrew N Van, Ryland L Miller, Nicole A Seider, Scott Marek, Annie Zheng, Dillan J Newbold, Kristen Scheidter, Benjamin P Kay, Abhinav K Jha, Aristeidis Sotiras, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion and differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) images makes their alignment a challenge. Typically, field map data are used to correct EPI distortions. Alignments achieved with field maps can vary greatly and depends on the quality of field map data. However, many public datasets lack field map data entirely. Additionally, reliable field map data is often difficult to acquire in high-motion pediatric or developmental cohorts. To address this, we developed Synth, a software package for distortion correction and …

Utilization Of Microwave Ablation As A Novel Approach For Refractory Chylothorax Following Esophagectomy: A Case Report, Khashayar Farahnak, Alejandro De Filippis Falcon, Hailey M Shepherd, Carlos J Guevara, Mayank R Patel, G Alexander Patterson, Varun Puri, Daniel Kreisel, Ruben G Nava

2020-Current year OA Pubs

No abstract provided.

Logistical, Technical, And Radiation Safety Aspects Of Establishing A Radiopharmaceutical Therapy Program: A Case In Lutetium-177 Prostate-Specific Membrane Antigen (Psma) Therapy, Jacqueline E Zoberi, Jose Garcia-Ramirez, David Luechtefeld, Nichole M Maughan, Maxwell Amurao, Reiko Oyama, Brian C Baumann, Hiram A Gay, Jeff M Michalski

2020-Current year OA Pubs

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, …

Management Of Infusion-Related Reactions (Irrs) In Patients Receiving Amivantamab In The Chrysalis Study, Keunchil Park, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

METHODS: Patients treated with the approved dose of intravenous amivantamab (1050 mg, <80 kg; 1400 mg, ≥80 kg) in CHRYSALIS-an ongoing, phase 1 study in advanced EGFR-mutated NSCLC-were included in this analysis. IRR mitigations included split first dose (350 mg, day 1 [D1]; remainder, D2), reduced initial infusion rates with proactive infusion interruption, and steroid premedication before initial dose. For all doses, pre-infusion antihistamines and antipyretics were required. Steroids were optional after the initial dose.

RESULTS: As of 3/30/2021, 380 patients received amivantamab. IRRs were reported in 256 (67%) patients. Signs/symptoms of IRR included chills, dyspnea, flushing, nausea, chest discomfort, and vomiting. Most of the 279 IRRs were grade 1 or 2; grade 3 and 4 …

Mitochondrial Pyruvate Carrier Inhibition Initiates Metabolic Crosstalk To Stimulate Branched Chain Amino Acid Catabolism, Daniel Ferguson, Sophie J Eichler, Nicole K H Yiew, Jerry R Colca, Kevin Cho, Gary J Patti, Trevor M Shew, Andrew J Lutkewitte, Sandip Mukherjee, Kyle S Mccommis, Natalie M Niemi, Brian N Finck

2020-Current year OA Pubs

OBJECTIVE: The mitochondrial pyruvate carrier (MPC) has emerged as a therapeutic target for treating insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). We evaluated whether MPC inhibitors (MPCi) might correct impairments in branched chain amino acid (BCAA) catabolism, which are predictive of developing diabetes and NASH.

METHODS: Circulating BCAA concentrations were measured in people with NASH and type 2 diabetes, who participated in a recent randomized, placebo-controlled Phase IIB clinical trial to test the efficacy and safety of the MPCi MSDC-0602K (EMMINENCE; NCT02784444). In this 52-week trial, patients were randomly assigned to placebo (n = 94) or 250 mg …

Presentation And Prognosis Of Excessive Asymptomatic Atrial Ectopy In Children And Adolescents With Structurally And Functionally Normal Hearts, Thomas R Joyce, James J Joyce, Marye J Gleva, Sunita J Ferns

2020-Current year OA Pubs

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolving, but no studies have confirmed this. Adults with excessive PACs, however, are at increased risk for future sustained atrial arrhythmias and cardiovascular morbidity and mortality. Therefore, we sought to evaluate the clinical course of frequent PACs in asymptomatic children. Patients < 21 years old with numerous asymptomatic PACs (>50/24 hours) were retrospectively selected over a 10-year period. Demographics, clinical characteristics, and results of cardiovascular testing were tabulated. Two groups were defined: those with a significant (>20%) reduction in burden of atrial ectopy versus those with an insignificant …

Multidimensional Poverty Is Associated With Dementia Among Adults In Afghanistan, Jean-Francois Trani, Yiqi Zhu, Soobin Park, Dauod Khuram, Rahim Azami, Monib Rahim Fazal, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND: Multidimensional poverty is associated with dementia, but no evidence is available for countries in conflict.

METHODS: A cross-sectional study was conducted in two provinces of Afghanistan between February 15th 2022 and April 20th 2022 among adults age 50 and older. Multidimensional poverty included six dimensions of well-being and 16 indicators of deprivation. The Rowland Universal Dementia Assessment Scale measured dementia. Poverty between adults with and without dementia was examined, adjusting for sex. Associations between dementia and poverty were investigated using multivariate regression model.

FINDINGS: Of the 478 adults included, 89 (52.7%) had mild, and 25 (14.8%) had moderate to …

Outcome Prediction By The 2022 European Leukemianet Genetic-Risk Classification For Adults With Acute Myeloid Leukemia: An Alliance Study, Krzysztof Mrózek, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPA

Understanding Misimplementation In U.S. State Health Departments: An Agent-Based Model, Matt Kasman, Ross A Hammond, Rob Purcell, Louise Farah Saliba, Stephanie Mazzucca-Ragan, Margaret Padek, Peg Allen, Douglas A Luke, Sarah Moreland-Russell, Paul C Erwin, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The research goal of this study is to explore why misimplementation occurs in public health agencies and how it can be reduced. Misimplementation is ending effective activities prematurely or continuing ineffective ones, which contributes to wasted resources and suboptimal health outcomes.

METHODS: The study team created an agent-based model that represents how information flow, filtered through organizational structure, capacity, culture, and leadership priorities, shapes continuation decisions. This agent-based model used survey data and interviews with state health department personnel across the U.S. between 2014 and 2020; model design and analyses were conducted with substantial input from stakeholders between 2019 …

Air Pollution And Acute Kidney Injury In The U.S. Medicare Population: A Longitudinal Cohort Study, Whanhee Lee, Ziyad Al-Aly, Et Al.

2020-Current year OA Pubs

BACKGROUND: Recent studies have reported the association between air pollution exposure and reduced kidney function. However, it is unclear whether air pollution is associated with an increased risk of acute kidney injury (AKI).

OBJECTIVES: To address this gap in knowledge, we investigated the effect estimates of long-term exposures to fine particulate matter [PM

METHODS: This nationwide population-based longitudinal cohort study included 61,300,754 beneficiaries enrolled in Medicare Part A fee-for-service (FFS) who were

RESULTS: Exposure to

DISCUSSION: This study found an association between exposures to air pollution and the risk of the first hospital admission with AKI, and this association persisted …

The Who Aware (Access, Watch, Reserve) Antibiotic Book And Prevention Of Antimicrobial Resistance, Veronica Zanichelli, Michael Sharland, Bernadette Cappello, Lorenzo Moja, Haileyesus Getahun, Carmem Pessoa-Silva, Hatim Sati, Catharina Van Weezenbeek, Hanan Balkhy, Mariângela Simão, Sumanth Gandra, Benedikt Huttner

2020-Current year OA Pubs

Guidance on the appropriate use of antibiotics for common infections is lacking in many settings. The World Health Organization (WHO) has recently released

Axatilimab For Chronic Graft-Versus-Host Disease After Failure Of At Least Two Prior Systemic Therapies: Results Of A Phase I/Ii Study, Carrie L Kitko, Iskra Pusic, Et Al.

2020-Current year OA Pubs

PURPOSE: Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)-dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development.

PATIENTS AND METHODS: This phase I (phI)/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692) evaluated safety, tolerability, and efficacy of axatilimab in patients age ≥ 6 years with active cGVHD after ≥ 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and …

Myeloid Autophagy Genes Protect Mice Against Fatal Tnf- And Lps-Induced Cytokine Storm Syndromes, Ya-Ting Wang, Amy Sansone, Asya Smirnov, Christina L Stallings, Anthony Orvedahl

2020-Current year OA Pubs

ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); BECN1: beclin 1, autophagy related; CASP1: caspase 1; CASP4/CASP11: caspase 4, apoptosis-related cysteine peptidase; CIM: conditionally immortalized macrophage; CLP: cecal ligation and puncture; CSS: cytokine storm syndrome; DC: dendritic cell; IFNG/IFNγ: interferon gamma; IFNGR1: interferon gamma receptor 1; ip: intraperitoneal; iv: intravenous; IL12/p70: interleukin 12, p70 heterodimer; IL18: Interleukin 18; ITGAX/CD11c: integrin alpha X; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; LYZ2/LYSM: lysozyme 2; MAP1LC3A/LC3: microtubule-associated protein 1 light chain 3 alpha; RB1CC1/FIP200: RB1-inducible coiled-coil 1; S100A8/MRP8: S100 calcium binding protein A8 (calgranulin …

Visual Autism, Margaret Reynolds, Susan M. Culican

2020-Current year OA Pubs

No abstract provided.

Strategies To Prevent Clostridioides Difficile Infections In Acute-Care Hospitals: 2022 Update, Larry K Kociolek, Dale N Gerding, Ruth Carrico, Philip Carling, Curtis J Donskey, Ghinwa Dumyati, David T Kuhar, Vivian G Loo, Lisa L Maragakis, Monika Pogorzelska-Maziarz, Thomas J Sandora, David J Weber, Deborah Yokoe, Erik R Dubberke

2020-Current year OA Pubs

No abstract provided.

Area Deprivation Index And Segregation On The Risk Of Hiv: A U.S. Veteran Case-Control Study, Abiodun O Oluyomi, Angela L Mazul, Yongquan Dong, Donna L White, Christine M Hartman, Peter Richardson, Wenyaw Chan, Jose M Garcia, Jennifer R Kramer, Elizabeth Chiao

2020-Current year OA Pubs

BACKGROUND: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans.

METHODS: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of …

Nadph Oxidase 2 Limits Amplification Of Il-1Β-G-Csf Axis And An Immature Neutrophil Subset In Murine Lung Inflammation, Zhimin Song, Sourav Bhattacharya, Guangming Huang, Zev J Greenberg, Wei Yang, Juhi Bagaitkar, Laura G Schuettpelz, Mary C Dinauer

2020-Current year OA Pubs

The leukocyte NADPH oxidase 2 (NOX2) regulates inflammation independent of its antimicrobial activity. Inherited defects in NOX2 lead to chronic granulomatous disease (CGD), associated with recurrent bacterial and fungal infections, often with excessive neutrophilic inflammation that results in significant inflammatory burden and tissue damage. We previously showed that excessive leukotriene B4 (LTB4) production by NOX2-deficient mouse neutrophils was a key driver of elevated lung neutrophil infiltration in the initial response to pulmonary challenge with the model fungal particle zymosan. We now identify interleukin-1β (IL-1β) and downstream granulocyte colony-stimulating factor (G-CSF) as critical amplifying signals that augment and sustain neutrophil accrual …

Design Of The Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint Study (Confidence), Jennifer B Green, Amy K Mottl, George Bakris, Hiddo J L Heerspink, Johannes F E Mann, Janet B Mcgill, Masaomi Nangaku, Peter Rossing, Charlie Scott, Alain Gay, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone.

METHODS: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a …

Assessment Of Bladder Pressure And Discomfort Symptoms: How Do Overactive Bladder Differ From Interstitial Cystitis/Bladder Pain Syndrome Patients?, Angelíca Gousse, Joel Vetter, H Henry Lai

2020-Current year OA Pubs

BACKGROUND: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB.

METHODS: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed.

RESULTS: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way …