Medicine and Health Sciences Commons^™

Engineering Hyaluronic Acid For The Development Of New Treatment Strategies For Osteoarthritis, Yu Seon Kim, Farshid Guilak

2020-Current year OA Pubs

Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at slowing down disease progression and focus mainly on pain management. The field of tissue engineering has therefore been focusing on developing strategies that could be used not only to alleviate symptoms of OA but also to regenerate the damaged tissue. Hyaluronic acid (HA), an integral component of both the synovial fluid and articular cartilage, has gained widespread …

The Use Of Objective Assessments In The Evaluation Of Technical Skills In Cardiothoracic Surgery: A Systematic Review, Nabil Hussein, Jef Van Den Eynde, Connor Callahan, Alvise Guariento, Can Gollmann-Tepeköylü, Malak Elbatarny, Mahmoud Loubani

2020-Current year OA Pubs

OBJECTIVES: With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula.

METHODS: Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological …

Psychiatry Training In Autism Spectrum Disorder And Intellectual Disability: Ongoing Gaps And Emerging Opportunities, Natasha Marrus, Kathleen A. Koth, Jessica A. Hellings, Rachel Mcdonald, Mcleod Frampton Gwynette, Rebecca Muhle, William D. Lohr, Roma A. Vasa

2020-Current year OA Pubs

Children, adolescents, and adults with autism spectrum disorder and intellectual disability experience high rates of co-occurring psychiatric conditions throughout their lifetime. However, there is a shortage of psychiatrists to treat these populations. We evaluated how much education psychiatrists-in-training receive on how to care for individuals with autism spectrum disorder/intellectual disability. We found that in many psychiatry programs, residents receive limited training experiences in autism spectrum disorder/intellectual disability involving lectures and patient contact and that psychiatry program directors would benefit from more resources to strengthen education in autism spectrum disorder/intellectual disability.

Glutamine Metabolism Modulates Chondrocyte Inflammatory Response, Manoj Arra, Gaurav Swarnkar, Naga Suresh Adapala, Syeda Kanwal Naqvi, Lei Cai, Muhammad Farooq Rai, Srikanth Singamaneni, Gabriel Mbalaviele, Robert Brophy, Yousef Abu-Amer

2020-Current year OA Pubs

Osteoarthritis is the most common joint disease in the world with significant societal consequences but lacks effective disease-modifying interventions. The pathophysiology consists of a prominent inflammatory component that can be targeted to prevent cartilage degradation and structural defects. Intracellular metabolism has emerged as a culprit of the inflammatory response in chondrocytes, with both processes co-regulating each other. The role of glutamine metabolism in chondrocytes, especially in the context of inflammation, lacks a thorough understanding and is the focus of this work. We display that mouse chondrocytes utilize glutamine for energy production and anabolic processes. Furthermore, we show that glutamine deprivation …

Evaluation Of Sensitivity To Endocrine Herapy Index (Set2,3) For Response To Neoadjuvant Endocrine Therapy And Longer-Term Breast Cancer Patient Outcomes (Alliance Z1031), Vera J Suman, Lili Du, Tanya Hoskin, Meenakshi Anurag, Cynthia Ma, Isabelle Bedrosian, Kelly K Hunt, Matthew J Ellis, W Fraser Symmans

2020-Current year OA Pubs

PURPOSE: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis.

EXPERIMENTAL DESIGN: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or …

Gonadal Sex Patterns P21-Induced Cellular Senescence In Mouse And Human Glioblastoma, Lauren Broestl, Nicole M Warrington, Lucia Grandison, Tamara Abou-Antoun, Olivia Tung, Saraswati Shenoy, Miranda M Tallman, Gina Rhee, Wei Yang, Jasmin Sponagel, Lihua Yang, Najla Kfoury-Beaumont, Cameron M Hill, Sulaiman A Qanni, Diane D Mao, Albert H Kim, Sheila A Stewart, Monica Venere, Jingqin Luo, Joshua B Rubin

2020-Current year OA Pubs

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine …

Hypertension Treatment In Nigeria (Htn) Program: Rationale And Design For A Type 2 Hybrid, Effectiveness, And Implementation Interrupted Time Series Trial, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hypertension is the most common cardiovascular disease in Nigeria and contributes to a large non-communicable disease burden. Our aim was to implement and evaluate a large-scale hypertension treatment and control program, adapted from the Kaiser Permanent Northern California and World Health Organization HEARTS models, within public primary healthcare centers in the Federal Capital Territory, Nigeria.

METHODS: A type 2 hybrid, interrupted time series design was used to generate novel information on large-scale implementation and effectiveness of a multi-level hypertension control program within 60 primary healthcare centers in the Federal Capital Territory, Nigeria. During the formative phase, baseline qualitative assessments …

Comparison Of Modern Periacetabular Osteotomy For Hip Dysplasia With Total Hip Arthroplasty For Hip Osteoarthritis-10-Year Outcomes Are Comparable In Young Adult Patients, Frank W Parilla, Serena Freiman, Gail E Pashos, Susan Thapa, John C Clohisy

2020-Current year OA Pubs

Young adult patients with symptomatic acetabular dysplasia and marginal secondary osteoarthritis can be faced with the decision to either undergo periacetabular osteotomy (PAO) to relieve symptoms and slow osteoarthritis progression or wait until progression to more advanced disease and undergo total hip arthroplasty (THA). The decision can be difficult, and contemporary literature to guide these decisions is sparse. Therefore, we retrospectively assessed complication rate, survivorship and patient-reported clinical outcomes [modified Harris Hip score (mHHS), UCLA Activity score] in two, consecutive cohorts of patients aged 18-40 years that underwent either PAO for symptomatic acetabular dysplasia (mean age 28.9 years) or THA …

Peptide-Sirna Nanoparticles Targeting Nf-Κb P50 Mitigate Experimental Abdominal Aortic Aneurysm Progression And Rupture, Huimin Yan, Ying Hu, Antonina Akk, Samuel A Wickline, Hua Pan, Christine T N Pham

2020-Current year OA Pubs

Abdominal aortic aneurysm (AAA) is a progressive vascular condition associated with high risk of mortality if left untreated. AAA is an inflammatory process with excessive local production of extracellular matrix degrading enzymes, leading to dilatation and rupture of the abdominal aorta. We posit that targeting NF-κB, a signaling pathway that controls inflammation, will halt AAA progression and prevent rupture. In an elastase-induced AAA model we observed that NF-κB activation increased progressively post-elastase perfusion. Unexpectedly, we found that AAA progression was marked by predominant nuclear accumulation of the NF-κB p50 subunit at the exclusion of p65. Using the amphipathic peptide p5RHH …

Comparison Of Endoscopic Underlay And Over-Under Tympanoplasty Techniques For Type I Tympanoplasty, James W Bao, Kevin Y Zhan, Cameron C Wick

2020-Current year OA Pubs

Objective: To compare the indications and efficacy of endoscopic over-under tympanoplasty versus endoscopic underlay tympanoplasty.

Methods: Retrospective cohort study of patients undergoing type I endoscopic tympanoplasty via either an underlay or over-under technique by a single surgeon from 2017 to 2021. Patients were excluded if they had a concurrent mastoidectomy, ossiculoplasty, or advanced cholesteatoma defined by involvement of multiple subsites. Patient demographics, perforation size and location, middle ear status, preoperative and postoperative audiograms, and perforation closure were reviewed. Middle ear status was represented using the Ossiculoplasty Outcome Parameter Score (OOPS). The primary outcome was perforation closure at most recent follow-up …

External Validation Of The Fear Index In Borderline Acetabular Dysplasia, Maria T Schwabe, John C Clohisy, Elizabeth A Graesser, Cecilia Pascual-Garrido, Jeffrey J Nepple

2020-Current year OA Pubs

Background: Given the lack of established, externally validated criteria for the diagnosis of unstable hips, the Femoro-Epiphyseal Acetabular Roof (FEAR) index has been proposed as a useful tool for identifying hips with instability in the setting of borderline acetabular dysplasia.

Purposes: To (1) determine the external performance of the FEAR index in identifying hips with a clinical diagnosis of instability in the setting of borderline dysplasia and (2) assess the performance of the FEAR index compared with acetabular inclination or physeal scar angle alone.

Study Design: Cohort study (diagnosis); Level of evidence, 3.

Methods: The authors reviewed 176 patients with …

Fetal Loss In Pregnant Rhesus Macaques Infected With High-Dose African-Lineage Zika Virus, Lauren E. Raasch, Kevin K. Noguchi, Nicole A. Fuhler, Et Al

2020-Current year OA Pubs

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant …

Comparative Proteomics Of Adult Paragonimus Kellicotti Excretion/Secretion Products Released In Vitro Or Present In The Lung Cyst Nodule, Lucia S. Di Maggio, Kurt C. Curtis, Petra Erdmann-Gilmore, Robert S. W. Sprung, R. Reid Townsend, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

Paragonimus kellicotti is a zoonotic lung fluke infection, the agent of North American paragonimiasis, and an excellent model for other Paragonimus infections. The excretory/secretory proteins (ESP) released by parasites and presented at the parasite-host interface are frequently proposed to be useful targets for drugs and/or vaccines In vitro culture conditions may alter ESP compared to those produced in vivo. In order to investigate ESPs produced in vivo we took advantage of the fact that adult P. kellicotti reproduce in the lungs of experimentally infected gerbils in tissue cysts. We performed a mass-spectrometric analysis of adult P. kellicotti soluble somatic protein …

Difference Imaging From Single Measurements In Diffuse Optical Tomography: A Deep Learning Approach, Shuying Li, Menghao Zhang, Minghao Xue, Quing Zhu

2020-Current year OA Pubs

SIGNIFICANCE: "Difference imaging," which reconstructs target optical properties using measurements with and without target information, is often used in diffuse optical tomography (DOT) in vivo imaging. However, taking additional reference measurements is time consuming, and mismatches between the target medium and the reference medium can cause inaccurate reconstruction.

AIM: We aim to streamline the data acquisition and mitigate the mismatch problems in DOT difference imaging using a deep learning-based approach to generate data from target measurements only.

APPROACH: We train an artificial neural network to output data for difference imaging from target measurements only. The model is trained and validated …

Depression, Stigma And Social Isolation: The Psychosocial Trifecta Of Primary Chronic Cutaneous Lupus Erythematosus, A Cross-Sectional And Path Analysis, Cristina Drenkard, Kristina A Theis, Timothy T Daugherty, Charles G Helmick, Charmayne Dunlop-Thomas, Gaobin Bao, Laura Aspey, Tené T Lewis, S Sam Lim

2020-Current year OA Pubs

OBJECTIVE: Depression is common in individuals with chronic cutaneous lupus erythematosus (CCLE). However, how CCLE may impact patients' psychological well-being is poorly understood, particularly among disproportionally affected populations. We examined the relationships between depression and psychosocial factors in a cohort of predominantly Black patients with primary CCLE (CCLE without systemic manifestations).

METHODS: Cross-sectional assessment of individuals with dermatologist-validated diagnosis of primary CCLE. NIH-PROMIS short-forms were used to measure depression, disease-related stigma, social isolation and emotional support. Linear regression analyses (ɑ=0.05) were used to test an a priori conceptual model of the relationship between stigma and depression and the effect of …

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Brian A Van Tine, Et Al

2020-Current year OA Pubs

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Effects Of A Liquefied Petroleum Gas Stove Intervention On Gestational Blood Pressure: Intention-To-Treat And Exposure-Response Findings From The Hapin Trial, Wenlu Ye, Victor G Davila-Roman, Et Al

2020-Current year OA Pubs

BACKGROUND: Approximately 3 to 4 billion people worldwide are exposed to household air pollution, which has been associated with increased blood pressure (BP) in pregnant women in some studies.

METHODS: We recruited 3195 pregnant women in Guatemala, India, Peru, and Rwanda and randomly assigned them to intervention or control groups. The intervention group received a gas stove and fuel during pregnancy, while the controls continued cooking with solid fuels. We measured BP and personal exposure to PM

RESULTS: Median 24-hour PM

CONCLUSIONS: In intention-to-treat, we found higher gestational BP in the intervention group compared with controls, contrary to expected. In …

Single Administration Of Intracameral Bimatoprost Implant 10 Μg In Patients With Open-Angle Glaucoma Or Ocular Hypertension, Felipe A Medeiros, Arsham Sheybani, Manjool M Shah, Marcos Rivas, Zhanying Bai, Erica Werts, Iqbal I K Ahmed, E Randy Craven

2020-Current year OA Pubs

INTRODUCTION: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension.

METHODS: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 …

Il-34 Deficiency Impairs Foxp3+ Treg Function In A Model Of Autoimmune Colitis And Decreases Immune Tolerance Homeostasis, Antoine Freuchet, Marco Colonna, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8

METHODS: We generated Il34

RESULTS: Here we report that the absence of expression of IL-34 in Il34

CONCLUSION: Altogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4

HIGHLIGHTS: -Absence of expression of IL-34 in Il34

Changes In Circulating Tumor Dna Reflect Clinical Benefit Across Multiple Studies Of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors, Diana Merino Vega, Aadel A Chaudhuri, Et Al

2020-Current year OA Pubs

PURPOSE: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.

PATIENTS AND METHODS: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell …

A Multidimensional Metabolomics Workflow To Image Biodistribution And Evaluate Pharmacodynamics In Adult Zebrafish, Madelyn M Jackstadt, Casey A Chamberlain, Steven R Doonan, Leah P Shriver, Gary J Patti

2020-Current year OA Pubs

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. …

Patient Preferences For Strategies To Improve Tuberculosis Diagnostic Services In Zambia, Andrew D Kerkhoff, Lophina Chilukutu, Sarah Nyangu, Mary Kagujje, Kondwelani Mateyo, Nsala Sanjase, Ingrid Eshun-Wilson, Elvin H Geng, Diane V Havlir, Monde Muyoyeta

2020-Current year OA Pubs

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.

Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.

Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was …

Mass Drug Administration Of Ivermectin, Diethylcarbamazine, Plus Albendazole Compared With Diethylcarbamazine Plus Albendazole For Reduction Of Lymphatic Filariasis Endemicity In Papua New Guinea: A Cluster-Randomised Trial, Moses Laman, Gary J Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua …

Factors Associated With Initiation And Continuation Of Endocrine Therapy In Women With Hormone Receptor-Positive Breast Cancer, Beomyoung Cho, Maria Pérez, Donna B Jeffe, Matthew W Kreuter, Julie A Margenthaler, Graham A Colditz, Ying Liu

2020-Current year OA Pubs

BACKGROUND: Despite benefits of endocrine therapy (ET) for patients with hormone-receptor (HR)-positive breast cancer, many patients do not initiate or discontinue ET against recommendations.

METHODS: We identified variables associated with ET initiation and continuation, analyzing pooled data from two longitudinal studies at a National Cancer Institute comprehensive cancer center in St. Louis, Missouri. The sample included 533 women with newly diagnosed, non-metastatic, HR-positive breast cancer who completed interviews at enrollment and 6, 12, and 24 months after definitive surgical treatment. Logistic regression models estimated the adjusted odds ratio and 95% confidence interval (aOR [95% CI]) for each of self-reported ET …

Phase I Trial Of The Dll3/Cd3 Bispecific T-Cell Engager Bi 764532 In Dll3-Positive Small-Cell Lung Cancer And Neuroendocrine Carcinomas, Martin Wermke, Enriqueta Felip, Valentina Gambardella, Yasutoshi Kuboki, Daniel Morgensztern, Zohra Oum' Hamed, Meiruo Liu, Matus Studeny, Taofeek K Owonikoko

2020-Current year OA Pubs

Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 …

Frontline Polatuzumab Vedotin For Diffuse Large B-Cell Lymphoma: A Survey Of Clinician Impressions, Ajay Major, Edward R Scheffer Cliff, Daniel A Ermann, Urshila Durani, David A Russler-Germain

2020-Current year OA Pubs

In the POLARIX trial, pola-R-CHP demonstrated improved progression-free survival (PFS) compared to R-CHOP in untreated intermediate- to high-risk DLBCL. We surveyed practicing clinicians regarding their interpretation of POLARIX, including impressions of efficacy, safety, and cost. Of 174 respondents, most from academic centers (82%) in the United States (57%), 70% stated they would not replace R-CHOP with pola-R-CHP due to insufficient PFS difference, lack of overall survival benefit, and excessive cost. Respondents not recommending pola-R-CHP expressed concerns about financial implications for both society and patients. We observed considerable heterogeneity in both study interpretation and plans for real-world implementation of pola-R-CHP.

New And Known Predictors Of The Postthrombotic Syndrome: A Subanalysis Of The Attract Trial, Félix Rinfret, Chu-Shu Gu, Suresh Vedantham, Susan R Kahn

2020-Current year OA Pubs

Introduction: Postthrombotic syndrome (PTS) remains associated with significant clinical and economic burden. This study aimed to investigate known and novel predictors of the development of PTS in participants of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) trial.

Methods: We used multivariable logistic regression to identify baseline and postbaseline factors that were predictive of the development of PTS during study follow-up, as defined by a Villalta score of 5 or greater or the development of a venous ulcer from 6 to 24 months after enrollment.

Results: Among 691 patients in the study cohort (all had proximal deep …

Association Of Endocrine Therapy Initiation Timeliness With Adherence And Continuation In Low-Income Women With Breast Cancer, Nikita Sood, Ying Liu, Min Lian, Tracy Greever-Rice, Jill Lucht, Chester Schmaltz, Graham A Colditz

2020-Current year OA Pubs

Importance: Though adjuvant endocrine therapy (AET) has proven efficacy in treating hormone receptor-positive (HR-positive) breast cancer, patient adherence to AET and continuation of treatment as recommended by guidelines remain suboptimal, especially for low-income patients.

Objective: To quantify timelines for initiating AET and assess their association with short- and long-term adherence and continuation of AET in low-income women with breast cancer.

Design, Setting, and Participants: This population-based retrospective cohort study included women younger than 65 years diagnosed with first primary HR-positive breast cancer between January 1, 2007, and December 31, 2013, followed up for 5 years after the first use of …

Nivolumab Plus Rucaparib For Metastatic Castration-Resistant Prostate Cancer: Results From The Phase 2 Checkmate 9kd Trial, Karim Fizazi, Margitta Retz, Daniel P Petrylak, Jeffrey C Goh, Jose Perez-Gracia, Louis Lacombe, Stefanie Zschäbitz, Mauricio Burotto, Hakim Mahammedi, Gwenaelle Gravis, Diogo Assed Bastos, Steven L Mccune, Juan Carlos Vázquez Limón, Edmond M Kwan, Daniel Castellano, Aude Fléchon, Fred Saad, Marc-Oliver Grimm, David R Shaffer, Andrew J Armstrong, Prabhu Bhagavatheeswaran, Neha P Amin, Keziban Ünsal-Kaçmaz, Xuya Wang, Jun Li, Andrea Loehr, Russell K Pachynski

2020-Current year OA Pubs

BACKGROUND: CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib.

METHODS: CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 …

Robustness And Reproducibility Of An Artificial Intelligence-Assisted Online Segmentation And Adaptive Planning Process For Online Adaptive Radiation Therapy, John W Chapman, Dao Lam, Bin Cai, Geoffrey D Hugo

2020-Current year OA Pubs

Clinical implementation of online adaptive radiation therapy requires initial and ongoing performance assessment of the underlying auto-segmentation and adaptive planning algorithms, although a straightforward and efficient process for this in phantom is lacking. The purpose of this work was to investigate robustness and repeatability of the artificial intelligence-assisted online segmentation and adaptive planning process on the Varian Ethos adaptive platform, and to develop an end-to-end test strategy for online adaptive radiation therapy. Five synthetic deformations were generated and applied to a computed tomography image of an anthropomorphic pelvis phantom, and reference treatment plans were generated from each of the resulting …