tbuckley/cabot-search huggingface dataset:
Fractionated Gemtuzumab Ozogamicin Combined with Intermediate-Dose Cytarabine and Daunorubicin As Salvage Therapy in Very High Risk AML Patients: A Bridge to Reduced Intensity Conditioning Transplant?
Authors: Etienne Paubelle, Sophie Ducastelle, Helene Labussiere, Franck E. Nicolini, Fiorenza Barraco, Adriana Plesa, Gilles A. Salles, Eric Wattel, Xavier Thomas
Journal: Blood (2016)
Effect of increasing Medicaid coverage in Medicaid expansion states on stage at presentation for urologic malignancies.
Authors: Xiaosong Meng, Hersh Trivedi, Alexander P. Kenigsberg, Rashed Ghandour, Vitaly Margulis, Aditya Bagrodia, Yair Lotan, Solomon L. Woldu
Journal: Journal of Clinical Oncology (2020)

400 Background: Medicaid Expansion (ME) was introduced by the Affordable Care Act to improve access to care for low income individuals by increasing the annual income limits to 138% of the poverty line. However, not all states have elected to participate in ME. Using the National Cancer Database (NCDB), we sought to assess the effects of participation in ME on the four most common urologic malignancies. Methods: The NCDB was queried for bladder, prostate, kidney and testis cancer from 2012-2016, to span the time period two years before and two years after the main ME which took place in 2014. Trends in insurance status at time of diagnosis and effects on stage at presentation before and after ME were analyzed. Results: The percentage of patients with Medicaid coverage at the time of diagnosis for all four urologic malignancies increased significantly after 2014, with a commiserate decrease in the percentage of uninsured patients (Table). By 2016, significantly more patients had Medicaid coverage at diagnosis in ME states compared to those in Non-ME states (bladder 5.0% vs 2.5%, prostate 5.9% vs 2.2%, kidney 9.7% vs 4.1%, 19.5% vs 7.2%, all p &lt; 0.01). However, the stage at presentation for all four urologic malignancies did not significantly differ for patients in ME versus non-ME states. Conclusions: Despite an increase in the proportion of patients with Medicaid coverage after 2014, surprisingly, there was not an associated change in stage at presentation for urologic malignancies in ME states. Further long-term analysis is necessary to evaluate if expanded Medicaid coverage impacts overall survival in this patient population.[Table: see text]
Synthetic immunity by remote control
Authors: Lena Gamboa, Ali H. Zamat, Gabriel A. Kwong
Journal: Theranostics (2020)

Cell-based immunotherapies, such as T cells engineered with chimeric antigen receptors (CARs), have the potential to cure patients of disease otherwise refractory to conventional treatments.Early-on-treatment and long-term durability of patient responses depend critically on the ability to control the potency of adoptively transferred T cells, as overactivation can lead to complications like cytokine release syndrome, and immunosuppression can result in ineffective responses to therapy.Drugs or biologics (e.g., cytokines) that modulate immune activity are limited by mass transport barriers that reduce the local effective drug concentration, and lack site or target cell specificity that results in toxicity.Emerging technologies that enable site-targeted, remote control of key T cell functions -including proliferation, antigen-sensing, and target-cell killing -have the potential to increase treatment precision and safety profile.These technologies are broadly applicable to other immune cells to expand immune cell therapies across many cancers and diseases.In this review, we highlight the opportunities, challenges and the current state-of-the-art for remote control of synthetic immunity.
Pregnancy Outcome in Chronic Myeloid Leukemia Patients on Imatinib Therapy
Authors: S. Shankar, S. Dasgupta, S. Mukhopadhyay, D. Bhattacharya(Majumdar), F.H. Gharami, S. Koner, U.K. Roy, J. Basak, A. Mukhopadhyay
Journal: Annals of Oncology (2012)
Pembrolizumab for Early Triple-Negative Breast Cancer
Authors: Peter Schmid, Javier Cortes, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Theodoros Foukakis, Peter A. Fasching, Fatima Cardoso, Michael Untch, Liyi Jia, Vassiliki Karantza, Jing Zhao, Gursel Aktan, Rebecca Dent, Joyce O’Shaughnessy
Journal: New England Journal of Medicine (2020)

Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.
Skin Staphylococcus aureus Colonization is Associated with Persistent Moderate-to-severe Atopic Dermatitis in Children
Authors: Tammy Gonzalez, Asel Baatyrbek Kyzy, John Kroner, Hua He, Lisa Martin, David Haslam, Jocelyn Biagini Myers, Gurjit Khurana Hershey, Andrew Herr
Journal: Journal of Allergy and Clinical Immunology (2020)
Tolerance To Baked Foods In Patients with Eosinophilic Esophagitis Associated with IgE Mediated Cow's Milk Allergy or Egg Allergy
Authors: Giovanna Lucy Cortez Aliaga, Pablo Torres, Patricia Salles-Cunha, Fabio Morato De Castro, Ariana Yang
Journal: Journal of Allergy and Clinical Immunology (2020)
Genomic profiling of prostate cancer at a diverse academic center.
Authors: Robert Lopez, Anna C. Ferrari, Sanjay Goel, Stephen Peeke, Janaki Neela Sharma, Niraj Konchady Shenoy, Benjamin Adam Gartrell
Journal: Journal of Clinical Oncology (2020)

64 Background: According to recent reports, ~1 in 4 patients with metastatic prostate cancer may harbor alterations in DNA damage repair (DDR) genes. Clinical trial data demonstrates that prostate cancer patients with DDR mutations may respond to poly-ADP ribose polymerase (PARP) inhibitors. Less is known about the mutational profile in minority patients with prostate cancer. We sought to determine the genomic profile of prostate cancer in an ethnically diverse patient population at a single center. Methods: We performed a retrospective review of men with prostate cancer at the Montefiore-Einstein Cancer Center who had next generation sequencing (NGS) with FoundationOne solid tumor testing between 2/2016 - 8/2019. Individual chart review was used to obtain clinical and demographic data including self-reported race/ethnicity. Results: NGS was attempted on archival tissue from 95 patients and results were obtained for 85. Among patients with results, the self-reported race/ethnicity was: Hispanic (H) 37.6%, Non-Hispanic Black (NHB) 52.9%, Non-Hispanic White (NHW) 4.7%, and Other (O) 4.7%. At the time of tissue sampling, 61 patients had metastatic disease and 10 were castration-resistant. 63 samples were from the prostate, 7 from bone, 7 from lymph node, 3 from liver and 5 from other soft tissue sites. The most commonly altered genes included: TP53 (26%), TMPRSS2-ERG fusion (23%), and PTEN (17%). Alterations in the androgen receptor were identified in 5 samples (all with CRPC). 32.8% had alterations in DDR genes including BRCA2 9 (10.6%), ATM 7 (8.2%), ATR 4 (4.7%), BRIP1 2 (2.3%), CDK12 3 (3.5%), FANCA 2 (2.3%), and PALB2 1 (1.2%). Alterations in mismatch repair genes (MSH2, MLH1, MSH6, PMS2) were present in 4 (4.7%) patients (3 of these were MSI-H). In samples where tumor mutational burden (TMB) was reported, 4 (4.7%) were TMB-high (3 MSI-H and 1 with POLE mutation). Conclusions: DDR gene mutations are common in this primarily minority population. As DDR mutations become more common in the CRPC setting, our data may underestimate the frequency of DDR mutations as only 10 patients had CRPC at the time of tissue sampling. Minority men, like all men, with prostate cancer should be considered for genomic analysis as results are likely to guide therapeutic decisions.
IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses
Authors: Ji Won Han, Pil Soo Sung, Seon-Hui Hong, Hoyoung Lee, June Young Koh, Hyojin Lee, Scott White, Joel N. Maslow, David B. Weiner, Su-Hyung Park, Moonsup Jeong, Jeong Heo, Sang Hoon Ahn, Eui-Cheol Shin
Journal: Journal of Hepatology (2020)
Cell cycLe inhibitiON to target the EVolution of urOthelial cancer (CLONEVO): A single-arm, open-label window-of-opportunity trial of neoadjuvant abemaciclib in platinum-ineligible muscle invasive bladder cancer patients.
Authors: Jones Nauseef, Panagiotis J. Vlachostergios, Ana M. Molina, David M. Nanus, Cora N. Sternberg, Timothy D McClure, Douglas Scherr, M. Laura Martin, Giorgio Inghirami, Olivier Elemento, Scott T. Tagawa, Bishoy Morris Faltas
Journal: Journal of Clinical Oncology (2020)

TPS606 Background: The standard of care for clinically localized muscle-invasive bladder cancer (MIBC) is neoadjuvant platinum-based combination chemotherapy followed by radical cystectomy (RC). Up to 40% of patients (pts) are ineligible to receive cisplatin and proceed to RC without any neoadjuvant therapy. We and others have demonstrated enrichment of molecular alterations in cell cycle genes in MIBC, including copy number losses of CDKN2A in 41% of pts. Abemaciclib is a unique CDK4/6 inhibitor with single agent activity and a target kinome distinct from other CDK4/6 inhibitors. We have demonstrated that CRISPR knockout of CDKN2A increases susceptibility to abemaciclib in bladder cancer cell lines. Beyond tumor-intrinsic effects, abemaciclib also modulates the tumor microenvironment (TME) via upregulating human endogenous retroviral elements and increasing T cell infiltration. Methods: Cell cycLe inhibitiON to target the EVolution of urOthelial cancer (CLONEVO) is a single arm, window-of-opportunity trial of neoadjuvant abemaciclib which will evaluate tumor cell and TME changes in response to abemaciclib. Enrolled pts must be ineligible for platinum-based neoadjuvant therapy for resectable MIBC. Pts receive abemaciclib (200 mg BID PO) for 4 weeks prior to RC. Tumor tissue collected via transurethral resection of bladder tumor (TURBT) and residual tumor at RC undergo single cell RNA sequencing and whole-exome sequencing. Patient-derived organoids and xenografts are generated for a co-clinical trial of abemaciclib alone or in combination. The primary endpoint is the measurement of changes in cell cycle dynamics. Secondary objectives are assessment of toxicity via NCI CTCAE v 5.0 and pathologic downstaging of MIBC. We will perform targeted sequencing of a panel of cell cycle genes in serial plasma and urine cell free DNA to evaluate changes in the variant allele fractions of somatic alterations. The novel design of this trial allows dynamic in vivo assessment of tumor changes and creates a new paradigm for studying tumor evolution in real time. Clinical trial information: NCT03837821.
Electronic Medication Monitoring vs. Self-Reported Use of Inhaled Corticosteroids and Short Acting Beta2 Agonists in Adult Patients with Uncontrolled Asthma
Authors: Leanne Kaye, Rahul Gondalia, Candy Gonzalez, Brittney Adams, Linda Zhu, PRISCILLIA QUAN, Naomi BenIsrael Olive, Madeleine Shalowitz, David Stempel
Journal: Journal of Allergy and Clinical Immunology (2020)
Subtypes of severe asthma based on a combination of blood eosinophil counts and levels of exhaled nitric oxide
Authors: Tomoyuki Soma, Yuki Hoshino, Ryu Sekiya, Yoshitaka Uchida, Erika Naito, Kazuki Katayama, Kazuyuki Nakagome, Makoto Nagata
Journal: Journal of Allergy and Clinical Immunology (2020)
Authors’ reply to Shaffer and colleagues
Authors: Ameena Goga, Yagespari Singh, Debra Jackson, Yogan Pillay, Sanjana Bhardwaj, Witness Chirinda, Chika Hayashi, Shaffiq Essajee, Priscilla Idele
Journal: BMJ (2020)

We appreciate the response from colleagues at the World Health Organization (WHO) to our article on the complexities around attaining the targeted case rate in high HIV prevalence settings to validate the elimination of mother-to-child HIV transmission (EMTCT) programme.12 Our short analysis article focused specifically on vertical transmission of HIV, so we did not reference the syphilis related information in the 2014 and 2017 WHO documents.34

Our article had two main aims: to show readers of The BMJ that true elimination of vertical HIV transmission is complex and challenging and to supplement current discourse on the ongoing …
Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial
Authors: Sarah Fidler, Wolfgang Stöhr, Matt Pace, Lucy Dorrell, Andrew Lever, Sarah Pett, Sabine Kinloch-de Loes, Julie Fox, Amanda Clarke, Mark Nelson, John Thornhill, Maryam Khan, Axel Fun, Mikaila Bandara, Damian Kelly, Jakub Kopycinski, Tomáš Hanke, Hongbing Yang, Rachel Bennett, Margaret Johnson, Bonnie Howell, Richard Barnard, Guoxin Wu, Steve Kaye, Mark Wills, Abdel Babiker, John Frater, Eric Sandström, Janet Darbyshire, Frank Post, Christopher Conlon, Jane Anderson, Mala Maini, Timothy Peto, Peter Sasieni, Veronica Miller, Ian Weller, Sarah Fidler, John Frater, Abdel Babiker, Wolfgang Stöhr, Sarah Pett, Lucy Dorrell, Matthew Pace, Natalia Olejniczak, Helen Brown, Nicola Robinson, Jakub Kopycinski, Hongbing Yang, Tomáš Hanke, Alison Crook, Steven Kaye, Myra McClure, Otto Erlwein, Andrew Lovell, Maryam Khan, Michelle Gabrielle, Rachel Bennett, Aminata Sy, Adam Gregory, Fleur Hudson, Charlotte Russell, Gemma Wood, Hanna Box, Cherry Kingsley, Katie Topping, Andrew Lever, Mark Wills, Axel Fun, Mikaila Bandara, Damian Kelly, Simon Collins, Alex Markham, Mary Rauchenberger, Yinka Sowunmi, Shaadi Shidfar, Dominic Hague, Mark Nelson, Maddalena Cerrone, Nadia Castrillo Martinez, Tristan Barber, Alexandra Schoolmeesters, Christine Weaver, Orla Thunder, Jane Rowlands, Christopher Higgs, Serge Fedele, Margherita Bracchi, Lervina Thomas, Peter Bourke, Nneka Nwokolo, Gaynor Lawrenson, Marzia Fiorino, Hinal Lukha, Sabine Kinloch-de Loes, Margaret Johnson, Alice Nightingale, Nnenna Ngwu, Patrick Byrne, Zoe Cuthbertson, Martin Jones, Tina Fernandez, Amanda Clarke, Martin Fisher, Rebecca Gleig, Vittorio Trevitt, Colin Fitzpatrick, Tanya Adams, Fiounnuala Finnerty, John Thornhill, Heather Lewis, Kristin Kuldanek, Julie Fox, Julianne Lwanga, Hiromi Uzu, Ming Lee, Simon Merle, Patrick O'Rourke, Isabel Jendrulek, Taras ZarkoFlynn, Mark Taylor, Juan Manuel Tiraboschi, Tammy Murray
Journal: The Lancet (2020)
Effect of obesity on response to checkpoint inhibitors in renal cell cancer.
Authors: Lakshminarayanan Nandagopal, Yousef Zakharia, Hesham Yasin, Kenneth Gerard Nepple, Mollie R. De Shazo, Eddy Shih-Hsin Yang, Rohan Garje, Arnab Basu, Peng Li, Lyse Norian
Journal: Journal of Clinical Oncology (2020)

634 Background: Response to checkpoint inhibitors (CPIs) for renal cell cancer (RCC) remains variable, with markers like PDL1 proving unreliable. Preclinical models suggest that obesity could affect CPI outcomes. We conducted a retrospective study on the effect of obesity on outcomes in RCC patients treated with CPIs. Methods: RCC patients treated with nivolumab +/- Ipilimumab at university of Alabama at Birmingham (UAB) and University of Iowa (UIOWA) from 2015 - 2018 were classified according to WHO standard definition of BMI as non-obese (NOB-&lt;30kg/m2) or obese (OB-&gt;30Kg/m2). Overall survival (OS) was defined as the interval from the first CPI dose to date of death or to last follow up date if patients were still alive. Progression free survival (PFS) was defined as the interval from the first dose of CPI to date of progression or date of death and censored at last follow-up date if patients were still alive without progression. Multivariable Cox proportional hazard regression model was used to evaluate the association between OS/PFS and obesity status, controlling for age, sex, race and number of prior therapies. All analyses were performed using SAS 9.4. Results: 84 patients with at least 6 months follow-up received a median of 9 doses of CPI with median follow of 72 weeks. 48 patients were NOB while 36 patients were OB, with 40 patients deceased at time of analysis. The most common response was stable disease in 45%, with CR in 5% and PR in 10% for a disease control rate of 63%. The median OS was 30 months in NOB patients and 20 months in the OB group. The 2 yr survival was 59% in the NOB group vs 28 % in the OB group with a HR of 0.60 (0.32-1.14; p=0.12). Median PFS was 13 months in the NOB group vs 7.3 months in the OB group with 2 yr PFS of 28% in the NOB group vs 5.5% in the OB group (HR 0.58 {0.35-0.98}; p=0.04). Conclusions: In this analysis of RCC patients treated with CPI, BMI &lt; 30 predicts better OS and PFS. Further studies are required to better understand the effect of BMI on CPI outcomes in RCC.[Table: see text]
Major Adverse Cardiovascular Events After 12 Months Among Patients With Acute Coronary Syndrome Receiving Loading Doses of Atorvastatin Prior to Planned PCI
Authors: Renato D. Lopes, Pedro G. M. de Barros e Silva, Lucas Petri Damiani, Renato Hideo Nakagawa Santos, John H. Alexander, Christopher B. Granger, Otavio Berwanger
Journal: JAMA (2020)

This study uses SECURE-PCI trial data to compare the effects of periprocedural loading doses of atorvastatin vs placebo on major adverse cardiac events (MACE) 12 months after randomization in patients with acute coronary syndrome (ACS) and planned invasive management.
Maladaptive Contractility of 3D Human Cardiac Microtissues to Mechanical Nonuniformity
Authors: Chenyan Wang, Sangmo Koo, Minok Park, Zacharias Vangelatos, Plansky Hoang, Bruce R. Conklin, Costas P. Grigoropoulos, Kevin E. Healy, Zhen Ma
Journal: Advanced Healthcare Materials (2020)

Cardiac tissues are able to adjust their contractile behavior to adapt to the local mechanical environment. Nonuniformity of the native tissue mechanical properties contributes to the development of heart dysfunctions, yet the current in vitro cardiac tissue models often fail to recapitulate the mechanical nonuniformity. To address this issue, a 3D cardiac microtissue model is developed with engineered mechanical nonuniformity, enabled by 3D-printed hybrid matrices composed of fibers with different diameters. When escalating the complexity of tissue mechanical environments, cardiac microtissues start to develop maladaptive hypercontractile phenotypes, demonstrated in both contractile motion analysis and force-power analysis. This novel hybrid system could potentially facilitate the establishment of "pathologically-inspired" cardiac microtissue models for deeper understanding of heart pathology due to nonuniformity of the tissue mechanical environment.
Patient and caregiver benefit-risk preferences for treatment in advanced urothelial carcinoma.
Authors: Andrea B. Apolo, M. Janelle Cambron-Mellott, Oliver Will, Brian S. Seal, Martine C. Maculaitis, Andrew Bernstein, Megan Epperson, Mara Lisa Jeffress, Yunes Doleh
Journal: Journal of Clinical Oncology (2020)

448 Background: Checkpoint blockade therapy has demonstrated improved survival in second-line urothelial carcinoma and is also active as first-line (1L) therapy in locally advanced / metastatic urothelial carcinoma (mUC) patients (PTs) who are cisplatin-ineligible / PD-L1 high or platinum-ineligible regardless of PD-L1 level. This study quantified trade-offs between efficacy and adverse events (AEs) associated with 1L treatments for mUC that PTs and caregivers (CGs) are willing to make. Methods: PTs with mUC and CGs were recruited via advocacy groups to complete a cross-sectional online survey assessing treatment preferences with a discrete choice experiment (DCE) employing descriptive language. In a series of tasks, PTs and CGs chose their preferred option from two alternative treatment profiles varying on six select attributes: overall survival (OS), progression-free survival (PFS), and AEs including: all grades (AG) neuropathy; and G3/4 nausea/vomiting, fatigue, and diarrhea. Hierarchical Bayesian modelling estimated preference weights for each attribute level. Results: PTs (N=152) had a mean age of 60 years; 68% had Stage 4 UC. CGs (N=151) had a mean age of 53 years and cared for PTs with a mean age of 62; most CGs (67%) cared for a PT with Stage 4 UC. While attributes had the same rank order of importance for both PTs and CGs, improving OS from 10 to 22 months was 31% more important than improving PFS from 2 to 10 months for PTs, whereas OS and PFS were more similarly valued by CGs. CGs placed less importance than PTs on OS relative to the importance of G3/4 nausea/vomiting, G3/4 diarrhea, and AG neuropathy (all P&lt;0.01). Despite these differences, OS was at least twice as important than reduction in AEs for both cohorts. To accept increases in G3/4 nausea/vomiting by 21%, G3/4 fatigue by 23%, G3/4 diarrhea by 7%, and AG neuropathy by 5%, OS would need to improve by 2.2, 2.3, 1.2, and 0.5 months (PTs) and 6.6, 5.5, 3.0, and 1.1 months (CGs), respectively. Conclusions: Trade-offs made between efficacy and specific AEs for mUC are nuanced between PTs and CGs, with CGs desiring larger OS benefits to accept higher AE risk. These findings suggest a need for deeper discussions between PTs, CGs and physicians about treatment decisions.
Comparative Assessment of Sunitinib-Associated Adverse Events (AES) as Potential Biomarkers of Efficacy in Metastatic Renal Cell Carcinoma (MRCC)
Authors: F. Donskov, M.D. Michaelson, I. Puzanov, M.P. Davis, G.A. Bjarnason, R.J. Motzer, X. Lin, D.P. Cohen, R. Wiltshire, B.I. Rini
Journal: Annals of Oncology (2012)
Prevalence of Strabismus and Its Impact on Vision-Related Quality of Life
Authors: Achim Fieß, Heike M. Elflein, Michael S. Urschitz, Konrad Pesudovs, Thomas Münzel, Philipp S. Wild, Matthias Michal, Karl J. Lackner, Norbert Pfeiffer, Stefan Nickels, Alexander K. Schuster
Journal: Ophthalmology (2020)