Digital Commons Network^™

Trpv4 Functional Status In Cystic Cells Regulates Cystogenesis In Autosomal Recessive Polycystic Kidney Disease During Variations In Dietary Potassium, Kyrylo Pyrshev, Anna Stavniichuk, Viktor N Tomilin, Naghmeh Hassanzadeh Khayyat, Guohui Ren, Oleg Zaika, Oleh Pochynyuk

Faculty, Staff and Student Publications

Mechanosensitive TRPV4 channel plays a dominant role in maintaining [Ca2+] i homeostasis and flow‐sensitive [Ca2+] i signaling in the renal tubule. Polycystic kidney disease (PKD) manifests as progressive cyst growth due to cAMP‐dependent fluid secretion along with deficient mechanosensitivity and impaired TRPV4 activity. Here, we tested how regulation of renal TRPV4 function by dietary K+ intake modulates the rate of cystogenesis and mechanosensitive [Ca2+] i signaling in cystic cells of PCK453 rats, a homologous model of human autosomal recessive PKD (ARPKD). One month treatment with both high KCl (5% K+) and KB/C (5% K+ with bicarbonate/citrate) diets significantly increased TRPV4 …

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, Alan Nicholas, G Alexander Patterson, Salama N Waqar, Eric M Toloza, Dan J Raz, Robert E Merritt, Dwight H Owen, David J Finley, Ciaran J Mcnamee, Justin D Blasberg, Edward B Garon, John D Mitchell, Robert C Doebele, Frank Baciewicz, Misako Nagasaka, Harvey I Pass, Katja Schulze, Ann Johnson, Paul A Bunn, Bruce E Johnson, Mark G Kris, David J Kwiatkowski, Ignacio I Wistuba, Jamie E Chaft, David P Carbone, Jay M Lee

Faculty, Staff and Student Publications

Objective: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

Methods: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …

Ideal Cardiovascular Health, Biomarkers, And Coronary Artery Disease In Persons With Hiv, Kathleen V Fitch, Gerald S Bloomfield, Carl J Fichtenbaum, Edgar T Overton, Judith A Aberg, Carlos D Malvestutto, Tricia H Burdo, Roberto C Arduino, Ken S Ho, Michael T Yin, Heather J Ribaudo, Steven K Grinspoon

Faculty, Staff and Student Publications

OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).

DESIGN: Cross-sectional.

METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).

RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH …

Eczema Monkeypoxicum In A Female Patient With Atopic Dermatitis, Shasta Theodore, Dora Marrufo, Jose Cadena, Patrick J Danaher

Faculty, Staff and Student Publications

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.

Invasive Mold Infections Following Hurricane Harvey-Houston, Texas, Jose A Serpa, Tom M Chiller, Luis Ostrosky-Zeichner, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.

METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.

RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 …

Transabdominal Cerclage During Pregnancy: A Retrospective Single Operator Series Over A Quarter Century

Faculty, Staff and Student Publications

OBJECTIVE: To describe the pregnancy outcomes and complications observed in a series of cases of transabdominal cerclage (TAC), which is reserved for highly selected women with recurrent mid-trimester pregnancy loss, due to cervical insufficiency.

METHODS: A retrospective audit covering 25 years (January 1, 1997 to December 31, 2021) was performed at the Obstetric Special Care division, Tygerberg Academic Hospital in Cape Town, South Africa. All 118 pregnancies from 94 procedures, operated and managed by the principal author were included for descriptive analysis.

RESULTS: Eighty-four (91.3%) of the 92 first pregnancies after first insertion had successful outcomes. All second and third …

Development Of The Illinois Surgical Quality Improvement Collaborative (Isqic): Implementing 21 Components To Catalyze Statewide Improvement In Surgical Care, Amy L Halverson, Remi Love, Lindsey Kreutzer, Allison R Dahlke, Brianna D'Orazio, Steven Reinhart, Katelyn Dienes, Mark Schumacher, Ying Shan, Christopher Quinn, Vivek N Prachand, Susan Sullivan, Kimberly A Cradock, Kelsi Boyd, William Hopkinson, Colleen Fairman, David Odell, Jonah J Stulberg, Cindy Barnard, Jane Holl, Ryan P Merkow, Anthony D Yang

Faculty, Staff and Student Publications

INTRODUCTION: In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.

METHODS: ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem. The components were developed from available evidence, a detailed …

Five Negative Symptom Domains Are Differentially Associated With Resting State Amplitude Of Low Frequency Fluctuations In Schizophrenia, Jesse T Edmond, Juan R Bustillo, Daniel H Mathalon, Judith M Ford, Kelvin O Lim, Bryon A Mueller, Adrian Preda, Daniel O'Leary, Gregory P Strauss, Anthony O Ahmed, Paul M Thompson, Neda Jahanshad, Peter Kochunov, Vince D Calhoun, Jessica A Turner, Theo G M Van Erp

Faculty, Staff and Student Publications

This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need …

Lingual Alveolar Soft Part Sarcoma In A 78-Year-Old Woman: A Case Report And Comprehensive Review Of The Literature From 1952 To 2022, Jillian R Aveni

Faculty, Staff and Student Publications

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes.

METHODS: We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. …

Independent Associations Of Neighborhood Deprivation And Patient-Level Social Determinants Of Health With Textbook Outcomes After Inpatient Surgery, Karyn B Stitzenberg, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: Assess associations of Social Determinants of Health (SDoH) using Area Deprivation Index (ADI), race/ethnicity and insurance type with Textbook Outcomes (TO).

SUMMARY BACKGROUND DATA: Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included.

METHODS: Three healthcare system cohort study using National Surgical Quality Improvement Program (2013-2019) linked with ADI risk-adjusted for frailty, case status and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, Emergency Department/Observation Stays and readmissions).

RESULTS: Cohort (34,251 cases) mean age 58.3 [SD=16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI>85, and 81.8% TO. Racial and …

Comparison Of Federated Kalman Filter And Autonomous Resilient Management Of All-Source Sensors (Armas) Framework For Fault Detection And Exclusion, Flavio Fernandes

Theses and Dissertations

In recent times, there is a great demand for resilient and robust PNT solutions. Current navigation systems rely heavily on GNSS to provide this solution. This dependence is a major concern and therefore it is prudent to use additional aids to provide the best solution possible. However, traditional methods to address this need require a nontrivial number of Kalman filters to maintain a fault-free solution. The federated filter approach provides an attractive alternative to the current solutions. In this thesis, we examine the use of the federated filter design to address this need in today’s integrated navigation systems. We compared …

A Look At The Global Impact Of Covid-19 Pandemic On Neurosurgical Services And Residency Training, Hebatalla Bakr

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has left an indelible effect on healthcare delivery and education system, including residency training. Particularly, neurosurgical departments worldwide had to adapt their operating model to the constantly changing pandemic landscape. This review aimed to quantify the reduction in neurosurgical operative volume and describe the impact of these trends on neurosurgical residency training.

METHODS: We performed a comprehensive search of PubMed and EMBASE between December 2019 and October 2022 to identify studies comparing pre-pandemic and pandemic neurosurgical caseloads as well as articles detailing the impact of COVID-19 on neurosurgery residency training. Statistical analysis of quantitative data was …

Defining The Role Of Ab Externo Xen Gel Stent In Glaucomatous Eyes With Prior Failed Surgical Intervention, Francisco Guevara-Abadia

Faculty, Staff and Student Publications

PURPOSE: To evaluate the safety and efficacy of Xen45 Gel stent (Xen; Allergan) in eyes that have failed prior surgical intervention, compared to traditional glaucoma drainage device (GDD) or continuous-wave cyclophotocoagulation (CPC). Since this population has low expected success rates with additional surgery, it is vital to compare to standard-of-care surgical options.

METHODS: Retrospective, single-center, case-control study of ab externo transconjunctival Xen shunt in eyes that have previously undergone trabeculectomy and/or GDD surgery. Postoperative data were collected for 18 months. Failure was defined as no light perception, additional glaucoma surgery required, or intraocular pressure (IOP) of < 6 mmHg after 6 weeks postoperatively.

RESULTS: Eighteen Xen eyes …

Properties Of A Combined Measure Of Reading And Writing: The Assessment Of Writing, Self-Monitoring And Reading (Awsm Reader)

Faculty, Staff and Student Publications

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach’s alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader’s relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and …

Racial And Ethnic Disparities In Acute Care Utilization Among Patients With Glomerular Disease, Salem Almaani, Daniel Cattran, Rasheed Gbadegesin, Dorey A Glenn, Larry A Greenbaum, Sandra Iragorri, Koyal Jain, Myda Khalid, Jason Kidd, Jeffrey Kopp, Richard Lafayette, Jerome C Lane, Francesca Lugani, Jordan G Nestor, Rulan S Parekh, Kimberly Reidy, David T Selewski, Christine B Sethna, C John Sperati, Katherine Tuttle, Katherine Twombley, Tetyana L Vasylyeva, Donald J Weaver, Scott E Wenderfer, Keisha Gibson

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort.

EXPOSURE: Race and ethnicity as a participant-reported social factor.

OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits.

ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization.

RESULTS: Black or Hispanic participants had lower SES and more …

Systemic Inflammatory Markers And Eeg Features Of Children With Fires Receiving Anakinra, Margo Hanerhoff, James J Riviello, Eyal Muscal

Faculty, Staff and Students Publications

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.

An Artificial Neural Network For Nasogastric Tube Position Decision Support, Darren Green, Ryan Grech, Srikanth Puttagunta, Mark Hall, David J Lowe

Faculty, Staff and Student Publications

PURPOSE: To develop and validate a deep learning model for detection of nasogastric tube (NGT) malposition on chest radiographs and assess model impact as a clinical decision support tool for junior physicians to help determine whether feeding can be safely performed in patients (feed/do not feed).

MATERIALS AND METHODS: A neural network ensemble was pretrained on 1 132 142 retrospectively collected (June 2007-August 2019) frontal chest radiographs and further fine-tuned on 7081 chest radiographs labeled by three radiologists. Clinical relevance was assessed on an independent set of 335 images. Five junior emergency medicine physicians assessed chest radiographs and made feed/do …

Direct Costs Of Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation (The Assists Trial), Angelo P Tanna, Ronald L Gross, Louis R Pasquale, David S Greenfield, Jeffrey M Liebmann, Robert N Weinreb

Faculty, Staff and Student Publications

PRCIS: The cost of cyclophotocoagulation is less than the cost of a second glaucoma drainage device.

PURPOSE: To compare the total direct costs of implantation of a second glaucoma drainage device (SGDD) with transscleral cyclophotocoagulation (CPC) for patients with inadequately controlled intraocular pressure (IOP) reduction, despite the presence of a preexisting glaucoma drainage device in the ASSISTS clinical trial.

METHODS: We compared the total direct cost per patient, including the initial study procedure, medications, additional procedures, and clinic visits during the study period. The relative costs for each procedure during the 90-day global period and the entire study period were …

Linoleic Acid Improves Piezo2 Dysfunction In A Mouse Model Of Angelman Syndrome, Francisco J Sierra-Valdez, Ugo Mayor, Lawrence T Reiter, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss …

The Effect Direction Should Be Taken Into Account When Assessing Small-Study Effects, Zhuo Meng, Chong Wu, Lifeng Lin

Faculty, Staff and Student Publications

OBJECTIVE: Studies with statistically significant results are frequently more likely to be published than those with non-significant results. This phenomenon leads to publication bias or small-study effects and can seriously affect the validity of the conclusion from systematic reviews and meta-analyses. Small-study effects typically appear in a specific direction, depending on whether the outcome of interest is beneficial or harmful, but this direction is rarely taken into account in conventional methods.

METHODS: We propose to use directional tests to assess potential small-study effects. The tests are built on a one-sided testing framework based on the existing Egger's regression test. We …

Evaluating Bone Marrow Dosimetry With The Addition Of Bone Marrow Structures To The Medical Internal Radiation Dose Phantom, Kristine L Ferrone, Charles E Willis, Fada Guan, Jingfei Ma, Leif E Peterson

Faculty, Staff and Student Publications

Background: Reliable estimates of radiation dose to bone marrow are critical to understanding the risk of radiation-induced cancers. Although the medical internal radiation dose phantom is routinely used for dose estimation, bone marrow is not defined in the phantom. Consequently, methods of indirectly estimating bone marrow dose have been implemented based on dose to surrogate volumes or average dose to soft tissue.

Methods: In this study, new bone marrow structures were implemented and evaluated to the medical internal radiation dose phantom in geant4, offering improved fidelity. The dose equivalent to the bone marrow was calculated across medical, occupational, and space …

The Microbiome And Its Impact On Allogeneic Hematopoietic Cell Transplantation, Florent Malard, Robert R Jenq

Faculty, Staff and Student Publications

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to …

Adding The X-Ray Bragg Reflection Physical Process In Crystal To The Geant4 Monte Carlo Simulation Toolkit, Part I: Reflection From A Crystal Slab, Fada Guan, Makoto Asai, Dirk A Bartkoski, Michael Kleckner, Ze'ev Harel

Faculty, Staff and Student Publications

X-ray diffraction from a solid crystal shows the wave nature of photons. It is an important electromagnetic (EM) physics process when X-ray photons interact with a crystal. Bragg diffraction, often called Bragg reflection, is a special case of the general form of X-ray diffraction, known as Laue diffraction. When the Bragg's law is met, the incident photon beam is reflected from the crystal plane behaving as a specular reflection at the Bragg angle. However, the Bragg reflection physical process has not been integrated into the general-purpose Monte Carlo simulation toolkit Geant4 for particle physics. In the current study, we developed …

Temporal Multi-Step Predictive Modeling Of Remission In Major Depressive Disorder Using Early Stage Treatment Data; Star*D Based Machine Learning Approach, Haitham Salem, Tung Huynh, Natasha Topolski, Benson Mwangi, Madhukar H Trivedi, A John Rush

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …

Customizable Landmark-Based Field Aperture Design For Automated Whole-Brain Radiotherapy Treatment Planning, Yao Xiao, Carlos Cardenas, Dong Joo Rhee, Tucker Netherton, Lifei Zhang, Raphael Douglas, Stephen Skett, Tina Patel, Chris Trauernicht, Caroline Chung, Hannah Simonds, Ajay Aggarwal, Laurence Court

Faculty, Staff and Student Publications

Purpose: To develop and evaluate an automated whole-brain radiotherapy (WBRT) treatment planning pipeline with a deep learning-based auto-contouring and customizable landmark-based field aperture design.

Methods: The pipeline consisted of the following steps: (1) Auto-contour normal structures on computed tomography scans and digitally reconstructed radiographs using deep learning techniques, (2) locate the landmark structures using the beam's-eye-view, (3) generate field apertures based on eight different landmark rules addressing different clinical purposes and physician preferences. Two parallel approaches for generating field apertures were developed for quality control. The performance of the generated field shapes and dose distributions were compared with the original …

Novel Genetic Regulators Of Fibrinogen Synthesis Identified By An In Vitro Experimental Platform, Dre'von A Dobson, Lori A Holle, Feng-Chang Lin, Jennifer E Huffman, James P Luyendyk, Nicholas L Smith, Alanna C Morrison, Alisa S Wolberg

Faculty, Staff and Student Publications

BACKGROUND: Fibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic and atherosclerotic diseases. Previous studies aimed to better understand the (patho) physiological actions of fibrinogen by characterizing the genomic contribution to circulating fibrinogen levels.

OBJECTIVES: Establish an in vitro approach to define functional roles between genes within these loci and fibrinogen synthesis.

METHODS: Candidate genes were selected on the basis of their proximity to genetic variants associated with fibrinogen levels and expression in hepatocytes and HepG2 cells. HepG2 cells were transfected with small interfering RNAs targeting …

Disruption Of Gcn2 Pathway Aggravates Vascular And Parenchymal Remodeling During Pulmonary Fibrosis, Diana Santos-Ribeiro, Marylène Lecocq, Michèle De Beukelaer, Stijn Verleden, Caroline Bouzin, Peter Dorfmuller, François Huaux, Rozenn Quarck, Harry Karmouty-Quintana, Maria-Rosa Ghigna, Juliette Bignard, Sophie Nadaud, Florent Soubrier, Sandrine Horman, Frederic Perros, Laurent Godinas, Charles Pilette

Faculty, Staff and Student Publications

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 (general control nonderepressible 2) gene (EIF2AK4 [eukaryotic translation initiation factor 2 alpha kinase 4]) were recently associated with pulmonary veno-occlusive disease. The aim of this study is to explore the involvement of the GCN2/eIF2α (eukaryotic initiation factor 2α) pathway in the development of PH during PF, in both human disease and in a laboratory animal model. Lung tissue from patients with PF with or without PH was collected at the …

First-In-Human Phase I Study Of The Ox40 Agonist Gsk3174998 With Or Without Pembrolizumab In Patients With Selected Advanced Solid Tumors (Engage-1), Sophie Postel-Vinay, Vincent K Lam, Willeke Ros, Todd M Bauer, Aaron R Hansen, F Stephen Hodi, Jennifer K Litton, Sandrine Aspeslagh, Karen A Autio, Frans L Opdam, Meredith Mckean, Neeta Somaiah, Stephane Champiat, Mehmet Altan, Anna Spreafico, Osama Rahma, Elaine M Paul, Christoph M Ahlers, Helen Zhou, Herbert Struemper, Shelby A Gorman, Maura Watmuff, Kaitlin M Yablonski, Niranjan Yanamandra, Michael J Chisamore, Emmett V Schmidt, Axel Hoos, Aurelien Marabelle, Jeffrey S Weber, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors.

METHODS: GSK3174998 (0.003-10 mg/kg) ± pembrolizumab (200 mg) was administered intravenously every 3 weeks using a continuous reassessment method for dose escalation. Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics, immunogenicity, pharmacodynamics, and clinical activity.

RESULTS: 138 patients were enrolled (45 (P1) and 96 (P2, including 3 crossovers)). Treatment-related adverse events occurred in 51% (P1) and 64% (P2) of patients, fatigue being the most …

Global Epidemiology And Clinical Outcomes Of Carbapenem-Resistant Pseudomonas Aeruginosa And Associated Carbapenemases (Pop): A Prospective Cohort Study, Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake M Hanson, Erica Herc, Keith S Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha S Kanj, Zhengyin Liu, Jose M Oñate, Robert A Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra L Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian M Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin E Stryjewski, Jose M Munita, David L Paterson, Scott Evans, Carol Hill, Keri Baum, Robert A Bonomo, Barry N Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, Yohei Doi, David Van Duin, Michael J Satlin

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.

METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day …

Meniscal And Articular Cartilage Predictors Of Outcome After Revision Acl Reconstruction: A 6-Year Follow-Up Cohort Study, Rick W Wright, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Thomas M Deberardino, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, John P Albright, Annunziato Ned Amendola, Jack T Andrish, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffery R Bechler, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler, John D Campbell, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Diane L Dahm, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Elizabeth A Garofoli, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Ltc Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York

Faculty, Staff and Student Publications

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction.

Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up.

Study design: Cohort study; Level of evidence, 3.

Methods: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and …