Medicine and Health Sciences Commons^™

Prognostic Value Of Tumor Volume Doubling Time In Lung-Metastatic Adenoid Cystic Carcinoma, Eduardo A Dal Lago, Luana G Sousa, Zixi Yang, Camilla O Hoff, Flavia Bonini, Matthew Sawyer, Kaiwen Wang, Whitney Lewis, Kareem A Wahid, Ehab Y Hanna, Adel El-Naggar, Clifton D Fuller, Suprateek Kundu, Myrna Godoy, Renata Ferrarotto

Faculty, Staff and Student Publications

Objectives: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT).

Methods: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), …

Exploring Ferroptosis-Inducing Therapies For Cancer Treatment: Challenges And Opportunities, Guang Lei, Boyi Gan

Faculty, Staff and Student Publications

Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis-an iron-dependent regulated cell death triggered by lipid peroxide accumulation-has gained prominence in cancer research in recent years. Ferroptosis-inducing therapies hold promise for overcoming resistance encountered with conventional treatments. However, challenges, including the lack of distinctive ferroptosis markers and the intricate role of ferroptosis within the tumor microenvironment, currently hinder the clinical translation of these therapies. This perspective article critically outlines these hurdles and highlights …

Cytogenetic And Molecular Associations With Outcomes In Higher-Risk Myelodysplastic Syndromes Treated With Hypomethylating Agents Plus Venetoclax, Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M Kadia, Gautam Borthakur, Courtney D Dinardo, Naval G Daver, Elias J Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood.

Experimental design: We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations …

Translational Potential Of A Contrast Agent For Fgs Applications In Pnets, Solmaz Aghaamiri, Jeannelyn S Estrella, Servando Hernandez Vargas, Mark W Hurd, Sukhen C Ghosh, Ali Azhdarinia, Naruhiko Ikoma

Faculty, Staff and Student Publications

No abstract provided.

Loss-Of-Function Mutation In Prmt9 Causes Abnormal Synapse Development By Dysregulation Of Rna Alternative Splicing, Lei Shen, Xiaokuang Ma, Yuanyuan Wang, Zhihao Wang, Yi Zhang, Hoang Quoc Hai Pham, Xiaoqun Tao, Yuehua Cui, Jing Wei, Dimitri Lin, Tharindumala Abeywanada, Swanand Hardikar, Levon Halabelian, Noah Smith, Taiping Chen, Dalia Barsyte-Lovejoy, Shenfeng Qiu, Yi Xing, Yanzhong Yang

Faculty, Staff and Student Publications

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between …

Targeting Prmt9-Mediated Arginine Methylation Suppresses Cancer Stem Cell Maintenance And Elicits Cgas-Mediated Anticancer Immunity, Haojie Dong, Xin He, Lei Zhang, Wei Chen, Yi-Chun Lin, Song-Bai Liu, Huafeng Wang, Le Xuan Truong Nguyen, Min Li, Yinghui Zhu, Dandan Zhao, Lucy Ghoda, Jonathan Serody, Benjamin Vincent, Leo Luznik, Ivana Gojo, Joshua Zeidner, Rui Su, Jianjun Chen, Ritin Sharma, Patrick Pirrotte, Xiwei Wu, Weidong Hu, Weidong Han, Binghui Shen, Ya-Huei Kuo, Jie Jin, Amandeep Salhotra, Jeffrey Wang, Guido Marcucci, Yun Lyna Luo, Ling Li

Faculty, Staff and Students Publications

Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival. Notably, PRMT9 inhibition promoted DNA damage and activated cyclic GMP-AMP synthase, which underlies the type …

Icos Costimulation In Combination With Ctla-4 Blockade Remodels Tumor-Associated Macrophages Toward An Antitumor Phenotype, Naveen Sharma, Xiaozhou Fan, Oluwatomisin T Atolagbe, Zhongqi Ge, Kelly N Dao, Padmanee Sharma, James P Allison

Faculty, Staff and Student Publications

We have previously demonstrated synergy between ICOS costimulation (IVAX; ICOSL-transduced B16-F10 cellular vaccine) and CTLA-4 blockade in antitumor therapy. In this study, we employed CyTOF and single-cell RNA sequencing and observed significant remodeling of the lymphoid and myeloid compartments in combination therapy. Compared with anti-CTLA-4 monotherapy, the combination therapy enriched Th1 CD4 T cells, effector CD8 T cells, and M1-like antitumor proinflammatory macrophages. These macrophages were critical to the therapeutic efficacy of anti-CTLA-4 combined with IVAX or anti-PD-1. Macrophage depletion with clodronate reduced the tumor-infiltrating effector CD4 and CD8 T cells, impairing their antitumor functions. Furthermore, the recruitment and polarization …

Mitochondrial Regulation Of Gpx4 Inhibition-Mediated Ferroptosis In Acute Myeloid Leukemia, Hiroki Akiyama, Ran Zhao, Lauren B Ostermann, Ziyi Li, Matthew Tcheng, Samar J Yazdani, Arman Moayed, Malcolm L Pryor, Sandeep Slngh, Natalia Baran, Edward Ayoub, Yuki Nishida, Po Yee Mak, Vivian R Ruvolo, Bing Z Carter, Aaron D Schimmer, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Resistance to apoptosis in acute myeloid leukemia (AML) cells causes refractory or relapsed disease, associated with dismal clinical outcomes. Ferroptosis, a mode of non-apoptotic cell death triggered by iron-dependent lipid peroxidation, has been investigated as potential therapeutic modality against therapy-resistant cancers, but our knowledge of its role in AML is limited. We investigated ferroptosis in AML cells and identified its mitochondrial regulation as a therapeutic vulnerability. GPX4 knockdown induced ferroptosis in AML cells, accompanied with characteristic mitochondrial lipid peroxidation, exerting anti-AML effects in vitro and in vivo. Electron transport chains (ETC) are primary sources of coenzyme Q

Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Hemorrhagic Stroke, Muhammad E Haque, Seth B Boren, James Mills, Kerry G Schneider, Maria Parekh, Stuart M Fraser, Ivo Bach, Praveen Hariharan, Pamela J Zelnick, Felix S Guerra Castanon, Asim Naveed, Muhammad Tariq, Octavio D Arevalo, Khader M Hasan, Miguel Escobar, Xiurong Zhao, Clark Sitton, Ponnada A Narayana, James C Grotta, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, …

New Horizons In Hyperpolarized13c Mri, Myriam M Chaumeil, James A Bankson, Kevin M Brindle, Shdema Epstein, Ferdia A Gallagher, Martin Grashei, Caroline Guglielmetti, Joshua D Kaggie, Kayvan R Keshari, Stephan Knecht, Christoffer Laustsen, Andreas B Schmidt, Daniel Vigneron, Yi-Fen Yen, Franz Schilling

Faculty, Staff and Student Publications

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons …

Automatic End-To-End Vmat Treatment Planning For Rectal Cancers, Kai Huang, Christine Chung, Ethan B Ludmir, Lifei Zhang, Constance A Owens, Jean Gumma-De La Vega, Jack Duryea, Yao Zhao, Xinru Chen, David Fuentes, Carlos E Cardenas, Tina Marie Briere, Sam Beddar, Laurence E Court, Prajnan Das

Faculty, Staff and Student Publications

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear.

PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs.

METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Comprehensive Analysis Of Transcription Factor-Based Molecular Subtypes And Their Correlation To Clinical Outcomes In Small-Cell Lung Cancer, Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Simon Heeke, Carl M Gay, Jiyeon Kim, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Lauren Averett Byers, John V Heymach, Yoon-La Choi, Se-Hoon Lee, Keunchil Park

Faculty, Staff and Student Publications

BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes.

METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype.

FINDINGS: IHC-based …

C2h2 Zinc Finger Transcription Factors Associated With Hemoglobinopathies, Xing Zhang, Fangfang Xia, Xiaotian Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin …

The Impact Of Individual-Level Income Predicted From The Brfss On The Association Between Insurance Status And Overall Survival Among Adults With Cancer From The Seer Program, Justin M Barnes, Kimberly J Johnson, Nosayaba Osazuwa-Peters, Matthew B Spraker

2020-Current year OA Pubs

INTRODUCTION: Among patients with cancer in the United States, Medicaid insurance is associated with worse outcomes than private insurance and with similar outcomes as being uninsured. However, prior studies have not addressed the impact of individual-level socioeconomic status, which determines Medicaid eligibility, on the associations of Medicaid status and cancer outcomes. Our objective was to determine whether differences in cancer outcomes by insurance status persist after accounting for individual-level income.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 18-64 year-old individuals with cancer from 2014-2016. Individual-level income was imputed using a model trained on Behavioral Risk …

Quality Assurance For Focused Ultrasound-Induced Blood-Brain Barrier Opening Procedure Using Passive Acoustic Detection, Chih-Yen Chien, Lu Xu, Jinyun Yuan, Siaka Fadera, Andrew H Stark, Umeshkumar Athiraman, Eric C Leuthardt, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure.

METHODS: Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the …

Drug-Induced Liver Injury In The Elderly: Consensus Statements And Recommendations From The Iq-Dili Initiative, Eric B Cohen, Meenal Patwardhan, Ritu Raheja, David H Alpers, Raul J Andrade, Mark I Avigan, James H Lewis, Don C Rockey, Francis Chui, Alexandru M Iacob, Camila C Linardi, Arie Regev, Jesse Shick, M Isabel Lucena

2020-Current year OA Pubs

The elderly demographic is the fastest-growing segment of the world's population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food …

Anatomical Registration Of Intracranial Electrodes. Robust Model-Based Localization And Deformable Smooth Brain-Shift Compensation Methods, Alejandro Omar Blenkmann, Sabine Liliana Leske, Anaïs Llorens, Jack J Lin, Edward F Chang, Peter Brunner, Gerwin Schalk, Jugoslav Ivanovic, Pål Gunnar Larsson, Robert Thomas Knight, Tor Endestad, Anne-Kristin Solbakk

2020-Current year OA Pubs

BACKGROUND: Intracranial electrodes are typically localized from post-implantation CT artifacts. Automatic algorithms localizing low signal-to-noise ratio artifacts and high-density electrode arrays are missing. Additionally, implantation of grids/strips introduces brain deformations, resulting in registration errors when fusing post-implantation CT and pre-implantation MR images. Brain-shift compensation methods project electrode coordinates to cortex, but either fail to produce smooth solutions or do not account for brain deformations.

NEW METHODS: We first introduce GridFit, a model-based fitting approach that simultaneously localizes all electrodes' CT artifacts in grids, strips, or depth arrays. Second, we present CEPA, a brain-shift compensation algorithm combining orthogonal-based projections, spring-mesh models, …

Neutrophils Are Indispensable For Adverse Cardiac Remodeling In Heart Failure, Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu, Gregg Rokosh

2020-Current year OA Pubs

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both …

Hspa9/Mortalin Inhibition Disrupts Erythroid Maturation Through A Tp53-Dependent Mechanism In Human Cd34+ Hematopoietic Progenitor Cells, Christopher Butler, Morgan Dunmire, Jaebok Choi, Gabor Szalai, Anissa Johnson, Wei Lei, Xin Chen, Liang Liu, Wei Li, Matthew J Walter, Tuoen Liu

2020-Current year OA Pubs

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. They are the most common myeloid blood cancers in American adults. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Around 10%-25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes, including HSPA9. The HSPA9 gene encodes for the protein mortalin, a highly conserved heat shock protein …

The Dmptool Nih Dmsp Templates Project, Nina Exner, Seonyoung Kim, Katy Smith

2020-Current year OA Pubs

The DMPTool NIH Data Management and Sharing Plan (DMSP) Templates Project was launched in response to the 2023 NIH Data Management and Sharing (DMS) Policy. This new policy introduced a more structured framework for DMS Plans, featuring six key elements, a departure from the 2003 NIH DMS policy. The project aimed to simplify the process for data librarians, research administrators, and researchers by providing a template with curated guidance, eliminating the need to navigate various policies and guidelines. The template breaks out each Plan section and subsection and provides related guidance and examples at the point of need. This effort …

Safety And Effectiveness Of Diazepam Nasal Spray In Male And Female Patients: Post Hoc Analysis Of Data From A Phase 3 Safety Study, James W Wheless, Robert Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine …

Enhancing Impact: A Call To Action For Equitable Implementation Science, Rachel C Shelton, Ross C Brownson

2020-Current year OA Pubs

Despite investments in evidence-based interventions and Implementation Science, most evidence-based interventions are not widely or routinely adopted, delivered, or sustained in many real-world community and healthcare settings. This gap is even greater in settings and populations experiencing numerous social and structural barriers to health, with important implications for persistent patterns in health inequities. In this Viewpoint, as part of a Special Issue on Advancing the Adaptability of Chronic Disease Prevention and Management through Implementation Science, we outline seven calls to action for the field of Implementation Science, with the goal of encouraging researchers, practitioners, and funders to be more intentional …

Feasibility Of Surface-Guidance Combined With Cbct For Intra-Fractional Breath-Hold Motion Management During Ethos Rt, Taeho Kim, Eric Laugeman, Kendall Kiser, Joshua Schiff, Shanti Marasini, Alex Price, H Michael Gach, Nels Knutson, Pamela Samson, Clifford Robinson, Casey Hatscher, Lauren Henke

2020-Current year OA Pubs

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs.

METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP …

Who's Essential Medicines And Aware: Recommendations On First- And Second-Choice Antibiotics For Empiric Treatment Of Clinical Infections, Lorenzo Moja, Sumanth Gandra, Et Al.

2020-Current year OA Pubs

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 …

The Performance Of 11 Fingertip Pulse Oximeters During Hypoxemia In Healthy Human Participants With Varied, Quantified Skin Pigment, Gregory Leeb, Leonid Shmuylovich, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation.

METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology …

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

Background

Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes.

Methods

We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT. Treatment included auto-contour and structure deformation of Organs at Risk (OARs) and target structures, with adjustments by the treating physician. Two plans were …

Addressing Subject Heterogeneity In Time-Dependent Discrimination For Biomarker Evaluation, Xinyang Jiang, Wen Li, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

Accurate discrimination has been the central goal in identifying biomarkers for monitoring disease progression and early detection. Acknowledging the fact that discrimination accuracy of biomarkers for a time-to-event outcome often changes over time, local measures such as the time-dependent receiver operating characteristic curve and its area under the curve (AUC) are used to assess time-dependent predictive discrimination. However, such measures do not address subject heterogeneity, although the impact of covariates including demographics, disease-related characteristics, and other clinical information on the discriminatory performance of biomarkers needs to be investigated before their clinical use. We propose the covariate-specific time-dependent AUC, a measure …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Randomized Controlled Trial Of The Cmr Immersive Virtual Reality (Ivr) Headset Training Compared To E-Learning For Operating Room Configuration Of The Cmr Versius Robot, Catherine L Eley, Varun Palaniappan, Abbie Carter, Opeyemi Sogaolu, James Horwood, Michael Davies, Jared Torkington, James Ansell

Faculty, Staff and Student Publications

Robotic surgery offers potential advantages over laparoscopic procedures, but the training for configuring robotic systems in the operating room remains underexplored. This study seeks to validate immersive virtual reality (IVR) headset training for setting up the CMR Versius in the operating room. This single-blinded randomized control trial randomised medical students with no prior robotic experience using an online randomiser. The intervention group received IVR headset training, and the control group, e-learning modules. Assessors were blinded to participant group. Primary endpoint was overall score (OS): Likert-scale 1-5: 1 reflecting independent performance, with increasing verbal prompts to a maximum score of 5, …