tbuckley/cabot-search huggingface dataset:
SHR3680, a novel antiandrogen, for the treatment of metastatic castration-resistant prostate cancer (mCRPC): A phase I/II study.
Authors: Xiaojian Qin, Weiqing Han, Hong Luo, Chuanjun Du, Qing Zou, Zhongquan Sun, Chaohong He, Shaoxing Zhu, Tie Chong, Xin Yao, Ben Wan, Weijie Gu, Dingwei Ye
Journal: Journal of Clinical Oncology (2020)

90 Background: SHR3680 is a novel and pure androgen-receptor (AR) antagonist that shows a potent antitumor activity against CRPC but with much less brain distribution than enzalutamide in preclinical study. In this first-in-human phase 1/2 study, the safety and efficacy of SHR3680 were assessed in patients with mCRPC. Methods: This phase 1/2 study was conducted in 11 hospitals in China. Patients with progressive mCRPC that was not previously treated with novel AR-targeted agents were eligible for this study. In the phase 1 part, patients received oral SHR3680 at a starting daily dose of 40 mg, which was subsequently escalated to 80 mg, 160 mg, 240 mg, 360 mg, and 480 mg. In phase 2, patients were randomized to receive one of three daily doses of SHR3680 (80 mg, 160 mg, and 240 mg). The primary endpoint in phase 1 was safety and tolerability, and in phase 2 was the proportion of patients with a PSA response (≥50% decrease of PSA level at week 12). Results: From Apr 2016 to Sep 2018, a total of 197 patients (median age 67 years, range 45−80; visceral metastases in 29 patients; previous chemotherapy history in 80 patients) were enrolled (phase 1, n = 18; phase 2, n = 179). No dose-limiting toxicities were reported and the maximum tolerated dose was not reached. Most adverse events were grade 1/2 (87.3%). The most common adverse events were anemia (22.8%), back pain (16.2%), and proteinuria (13.2%). The antitumor activity was observed at all doses, including PSA response in 134 (68.7%) of 195 evaluable patients, stabilized bone disease in 169 (86.7%) of 195 patients at week 12, and responses in soft tissue lesions in 22 (36.7%) of 60 patients. No obvious dose-related activity benefits were found. As of Sep 26, 2019, the median time to PSA progression was 36 weeks (95% CI 24−47), while that to radiological progression was 73 weeks (95% CI 49−96). As expected, patients without previous chemotherapy showed relatively longer time to PSA and radiological progression than those with previous chemotherapy. Conclusions: SHR3680 is safe and well tolerated, and exhibits high efficacy in mCRPC patients. Clinical trial information: NCT02691975.
Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China
Authors: Zunyou Wu, Jennifer M. McGoogan
Journal: JAMA (2020)

This Viewpoint summarizes key epidemiologic and clinical findings from all cases of coronavirus disease 2019 (COVID-19) reported through February 11, 2020, in mainland China, and case trends in response to government attempts to control and contain the infection.
Abstract 15381: Magnetic Resonance Elastography as a Potential Non-Invasive Diagnostic Tool for Patients With Heart Failure With Preserved Ejection Fraction
Authors: Arvin Arani, Shivaram P Arunachalam, Phillip J Rossman, Joshua D Trzasko, Kevin Glaser, Yi Sui, Kiaran McGee, Armando Manduca, Barry A Borlaug, Richard L Ehman, Philip A Araoz
Journal: Circulation (2017)

Introduction: Increased myocardial stiffness impairs diastolic filling and is associated with a range of cardiac diseases, even in asymptomatic patients. If severe, increased stiffness can cause he...
Comparative effectiveness of five treatment strategies for early-stage non-small cell lung cancer in the elderly.
Authors: Shervin Mohajer Shirvani, Jing Jiang, Joe Y. Chang, Daniel Richard Gomez, James Welsh, Stephen Swisher, Thomas A. Buchholz, Benjamin D. Smith
Journal: Journal of Clinical Oncology (2012)

7062 Background: Early-stage lung cancer incidence among older adults is expected to increase due to demographic trends and CT-based screening, yet optimal treatment in the elderly remains controversial. Using the SEER-Medicare cohort spanning 2001-2007, we determined survival outcomes associated with five strategies used in contemporary practice. Methods: Treatment strategy and covariates were determined in 10,923 patients age≥66 with stage IA-IB non-small cell lung cancer. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for lobectomy, sublobar resection, conventional radiation, stereotactic body radiotherapy (SBRT) and observation. In a second analysis, propensity-score matching was used for pairwise comparison of SBRT with other strategies. Results: Median age was 75 years and 29% had substantial comorbidity. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SBRT (1.1%). In unmatched Cox regression with median follow up of 3.2 years, SBRT was associated with the lowest risk of death within six months of diagnosis (HR 0.47; 95%CI 0.37-0.61; referent is lobectomy). After six months, sublobar resection and SBRT were associated with similar overall survival (P=0.51) and were both modestly worse than lobectomy. With propensity-score matching, survival after SBRT was similar to lobectomy (HR 0.90; 95%CI 0.64-1.27). Conventional radiation and observation were associated with poor outcomes in all analyses. Disease-specific survival outcomes followed similar trends. Conclusions: This population-based experience provides strong support of SBRT as an alternative to surgery or conventional radiation for select patient populations. Evaluation of this new therapy in randomized trials is urgently needed.
Acute patient-reported toxicities after proton therapy or intensity-modulated radiotherapy for prostate cancer.
Authors: Kimberly Gergelis, Miao Bai, Thomas Whitaker, David M. Routman, Mustafa Sir, Richard Choo
Journal: Journal of Clinical Oncology (2020)

305 Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p&lt;0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p&lt;0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p&lt;0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.
Prostate cancer CTC-RNA Assay: A new method for contemporary genomics and precision medicine via liquid biopsy.
Authors: Pai-Chi Teng, Yu Jen Jan, Jie-Fu Chen, Minhyung Kim, Nu Yao, Isla Garraway, Gina Chia-Yi Chu, Pin-Jung Chen, Jasmine Jiemei Wang, Yi-Te Lee, Yazhen Zhu, Leland WK Chung, Felix Y Feng, Michael Freeman, Sungyong You, Hsian-Rong Tseng, Edwin M. Posadas
Journal: Journal of Clinical Oncology (2020)

170 Background: Transcriptome-based analysis has begun to reshape the approach to prostate cancer (PC). Two different gene expression signatures have shown that PC can be divided into 3 subclasses reflecting luminal-basal biology. These subtypes point toward biological drivers that may strongly influence how care should be personalized including optimization of androgen receptor targeted therapy. The majority of work done in this area has been based on tissue-based gene expression. With the advent of newer nanotechnology platforms for isolation of circulating tumor cells (CTCs), profiling of PC gene expression from blood is now possible. Methods: We recruited 34 patients with metastatic castration resistant PC at Cedars-Sinai Medical Center who had available blood specimens prior to initiation of androgen receptor signaling inhibitor (ARSI, e.g. abiraterone, enzalutamide and apalutamide) therapy.We utilized the NanoVelcro Assays which allow for capture and release of CTCs with intact mRNA. Gene sets from the PCS and PAM50 signatures were re-reviewed to optimize signal detection in the blood and enriched for genes upregulated in PC. The NanoString nCounter platform was used for RNA profiling. Results: The final assay was tested in banked blood samples and provided classifications of patients that associated with clinical responsiveness to therapy. Validation was conducted to examine the performance of the CTC-specific PCS/PAM50 panel in public databases (including Prostate Cancer Transcriptome Atlas and GenomeDx). Our pilot study showed that the median overall survival was significantly worse in PCS1 patients. Conclusions: This study shows initial proof of principle that genomic classification in blood is possible using contemporary tool for blood component isolation and RNA profiling. Additional technical and clinical validations are needed prior to widespread implementation, but these methods may make it possible to increase the utilization of genomic classifiers in clinical studies and in practice.
Evaluation of adalimumab biosimilar in treatment of psoriatic arthritis with concomitant moderate to severe chronic plaque psoriasis: An open-labeled, prospective, pilot case series
Authors: Sujay Khandpur, Prateek Sondhi, Neha Taneja, Preeti Sharma, Dayasagar Das, Alpana Sharma, Vishnubatla Sreenivas
Journal: Journal of the American Academy of Dermatology (2020)
11O Prospective Comparison of Risk Assessment Tools in Early Breast Cancer: Correlation Analysis from the Phase III Wsg-Plan B Trial
Authors: O. Gluz, H.H. Kreipe, T. Degenhardt, M. Salem, R.E. Kates, S. Shak, C. Svedman, C. Liedtke, U. Nitz, N. Harbeck
Journal: Annals of Oncology (2012)
PD-L1 expression level in Chinese upper tract urothelial cancer (UTUC) patients and its correlation with pathological and clinical features.
Authors: Kaiwei Yang, Qun He, Dong Li, Wei Yu, Yi Song, Xinyu Yang, Xiyue Hu, Jun Zhu, Ting Li, Zhisong He
Journal: Journal of Clinical Oncology (2020)

553 Background: UTUC is a potentially lethal malignancy and PD1-1/PD-L1 antibodies have shown promising efficacy. Although it had been explored in patients of their PD-L1 expression level who were enrolled in clinical trials, most of them were not Chinese. China has a larger patient population in CKD patients, yet may cause a different level of PD-L1 expression. Methods: Patients of locally resectable disease were enrolled and tumor tissues were collected for VENTANA PD-L1 (SP263) Assay (Roch). High and Low expression levels were determined according to the interpretation guide. Clinical and pathological data were collected and statistical analyses were done by SPSS 20. Results: A total of 190 patients diagnosed with UTUC were enrolled. Forty-one (21.6%) patients were identified as high PD-L1 expression. PD-L1 expression were significantly higher in high tumor grade (p=0.001), higher T stage (≤T2 vs. &gt;T3, p=0.002), with divergent differentiation (squamous/ glandular/ sarcomatoid vs. pure UC, p=0.005), higher neutrophil/lymphocyte ratio (NLR≤3 vs. &gt;3, p=0.045) and higher platelet/lymphocyte ratio (PLR&lt;150 vs.≥150, p=0.006). Notably, patients with CKD stage 3 or higher (eGFR &lt;60ml/min/1.73m 2 ) had comparable PD-L1 high expression population (p=0.34). The HR for metastatic free survival was 2.65 in high expression patients (95% CI 1.17~5.97, p=0.019). Conclusions: China has a large population of UTUC with CKD stage 3 or higher who are ineligible for cisplatin and call for new treatment such as PD-L1/PD1 antibody. No difference was found in different CKD groups. UTUC seems to have lower proportion of PD-L1 high expression compared to bladder cancer. Whether it is due to more N-linked glycosylation that masked the detection or there might be other reasons inlayed stilled remain further study to find out.[Table: see text]
The Affordable Care Act at 10 Years — Its Coverage and Access Provisions
Authors: David Blumenthal, Sara R. Collins, Elizabeth J. Fowler
Journal: New England Journal of Medicine (2020)

The Affordable Care Act (ACA) was signed into law 10 years ago. This first of two Health Policy Reports reviewing the challenges and successes of the law focuses on the provisions of the law that expanded coverage. The ACA has reduced the number of Americans who are uninsured and the out-of-pocket health care costs for those with low incomes.
<b>Platelet-Rich Plasma Doesn’t Facilitate Achilles Tendon</b> Healing
Authors: Anita Slomski
Journal: JAMA (2020)

Platelet-rich plasma provided no benefit after acute Achilles tendon rupture, a trial in the BMJ reported. The autologous whole-blood product, which delivers a high concentration of platelets, leucocytes, growth factors, and cytokines, is used extensively in sports and orthopedic medicine.
Tanning bed use and depression in a preventive medicine cohort: The Cooper Center Longitudinal Study
Authors: Katie Kinser, Carolyn E. Barlow, David Leonard, Stephen W. Farrell, Andjelka Pavlovic, Helen G. Kaporis, E. Sherwood Brown, Benjamin L. Willis, Laura F. DeFina
Journal: Journal of the American Academy of Dermatology (2020)
Patterns of Treatment and Retreatment of Acute Attacks of Hereditary Angioedema (HAE) with Standard of Care (SOC) On-Demand Medication: Results from the APeX-2 Study
Authors: Emel Aygoren-Pursun, Douglas Johnston, William Lumry, Huamin Li, Aleena Banerji, Bruce Zuraw, Sandra Christiansen, Tamar Kinaciyan, Jana Hanzlikova, Richard Gower, Remi Gagnon, Marco Cicardi, Melanie Cornpropst, Sylvia Dobo, Kathryn Hutchinson, Heather Iocca, Eniko Nagy, Sharon Murray, William Sheridan, Jonathan Bernstein
Journal: Journal of Allergy and Clinical Immunology (2020)
The European TREatment of ATopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate‐to‐severe atopic eczema*
Authors: F.M. Vermeulen, L.A.A. Gerbens, J. Schmitt, M. Deleuran, A.D. Irvine, K. Logan, W. Ouwerkerk, C. Vestergaard, C. Flohr, P.I. Spuls
Journal: British Journal of Dermatology (2020)

For many years dermatologists have had access to few therapies for patients with moderate-to-severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well-known safety profiles, lower costs and wider availability.To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice.In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use.From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience.This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off-label therapies are also preferred as first-line choice of systemic therapy.
Interim Estimates of 2019–20 Seasonal Influenza Vaccine Effectiveness — United States, February 2020
Authors: Fatimah S. Dawood, Jessie R. Chung, Sara S. Kim, Richard K. Zimmerman, Mary Patricia Nowalk, Michael L. Jackson, Lisa A. Jackson, Arnold S. Monto, Emily T. Martin, Edward A. Belongia, Huong Q. McLean, Manjusha Gaglani, Kayan Dunnigan, Angie Foust, Wendy Sessions, Juliana DaSilva, Shoshona Le, Thomas Stark, Rebecca J. Kondor, John R. Barnes, David E. Wentworth, Lynnette Brammer, Alicia M. Fry, Manish M. Patel, Brendan Flannery
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

During the 2019-20 influenza season, influenza-like illness (ILI)* activity first exceeded the national baseline during the week ending November 9, 2019, signaling the earliest start to the influenza season since the 2009 influenza A(H1N1) pandemic. Activity remains elevated as of mid-February 2020. In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season, CDC estimates seasonal influenza vaccine effectiveness in preventing laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report used data from 4,112 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during October 23, 2019-January 25, 2020. Overall, vaccine effectiveness (VE) against any influenza virus associated with medically attended ARI was 45% (95% confidence interval [CI] = 36%-53%). VE was estimated to be 50% (95% CI = 39%-59%) against influenza B/Victoria viruses and 37% (95% CI = 19%-52%) against influenza A(H1N1)pdm09, indicating that vaccine has significantly reduced medical visits associated with influenza so far this season. Notably, vaccination provided substantial protection (VE = 55%; 95% CI = 42%-65%) among children and adolescents aged 6 months-17 years. Interim VE estimates are consistent with those from previous seasons, ranging from 40%-60% when influenza vaccines were antigenically matched to circulating viruses. CDC recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months because influenza activity is ongoing, and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses as well as other influenza viruses that might circulate later in the season.
Genomic correlates of response to PD-1 axis inhibitors (IO) in metastatic urothelial cancer (mUC) using explainable artificial intelligence (AI).
Authors: Sergiusz Wesolowski, Roberto Nussenzveig, Victor Sacristan Santos, John Esther, Divyam Goel, Umang Swami, Sumati Gupta, Benjamin Louis Maughan, Mark Yandell, Petros Grivas, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2020)

570 Background: AI is increasingly being used in clinical cancer genomics research. Probabilistic Graphical Models (PGMs) are AI algorithms that capture multivariate, mutli-level dependencies in complex patterns in large datasets while retaining human interpretability. We hypothesize that PGMs can identify clinical and genomic features that correlate with IO response in patients (pts) with mUC. Methods: In this retrospective study eligibility criteria were: diagnosis of mUC, receipt of IO for mUC, comprehensive genomic profiling data available from CLIA certified labs. The Bayesian Network (BN, PGM based AI) was used to discover clinical characteristics and selected genomic alterations relevant to IO response by RECIST 1.1 (investigator assessed). Results: Overall, 95 pts (73 men) with mUC were evaluated. 45 (47%) were ever smokers.The presented BN correctly captured the clinical landscape of mUC explaining significant relationship between included variables (p&lt;0.0001). Ever smokers and pts with de novo metastasis had higher TMB and better response to IO. Inactivating MLL2 alterations were more prevalent in non-smokers, and negatively correlated with response to IO. FGFR3 alterations did not predict response to IO. Significant associations are presented in Table. Conclusions: These hypothesis-generating data (by a novel approach, i.e. PGM based AI) showed that smoking and high-TMB were associated with improved response to IO; in contrast, inactivating MLL2 alternations and visceral metastasis predicted inferior response. FGFR3 alterations did not correlate with response. This model validated previous findings and found new hypothesis-generating relationship, such as altered MLL2 gene; external validation is needed.[Table: see text]
Dementia drugs should be reimbursed for the sake of responders
Authors: Tobias Damgaard
Journal: BMJ (2020)

I am surprised to hear of the French minister of health’s decision to stop funding dementia drugs.1 The reasoning is incomplete for several reasons.

Firstly, pharmacological treatments for dementia are not curative and cannot substitute non-pharmacological interventions. Caregivers know this. In Sweden, healthcare personnel already work hard to develop and integrate non-pharmacological interventions regularly; withdrawing reimbursement would not promote …
Clinical Significance of <i>TARP</i> Expression in Pediatric Acute Myeloid Leukemia
Authors: Barbara Depreter, Barbara De Moerloose, Karl Vandepoele, Anne Uyttebroeck, An Van Damme, Barbara Denys, Laurence Dedeken, Marie‐Françoise Dresse, Jutte Van der Werff Ten Bosch, Mattias Hofmans, Tessa Kerre, Bart Vandekerckhove, Jan Philippé, Tim Lammens
Journal: HemaSphere (2020)

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