tbuckley/cabot-search huggingface dataset:
Evaluation of high‐sensitivity C‐reactive protein and uric acid in vericiguat‐treated patients with heart failure with reduced ejection fraction
Authors: Frank Kramer, Sebastian Voss, Lothar Roessig, Bernd‐Wolfgang Igl, Javed Butler, Carolyn S.P. Lam, Aldo P. Maggioni, Sanjiv J. Shah, Burkert Pieske
Journal: European Journal of Heart Failure (2020)

Abstract Aims The effects of vericiguat vs. placebo on high‐sensitivity C‐reactive protein (hsCRP) and serum uric acid (SUA) were assessed in patients with heart failure with reduced ejection fraction (HFrEF) in the Phase 2 SOCRATES‐REDUCED study (NCT01951625). Methods and results Changes from baseline hsCRP and SUA values at 12 weeks with placebo and vericiguat (1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg, respectively) were assessed. The probability of achieving an hsCRP value of ≤3.0 mg/L or SUA value of &lt;7.0 mg/dL at week 12 was tested. Median baseline hsCRP and SUA levels were 3.68 mg/L [interquartile range (IQR) 1.41–8.41; n = 335] and 7.80 mg/dL (IQR 6.40–9.33; n = 348), respectively. Baseline‐adjusted mean percentage changes in hsCRP were 0.2%, −19.5%, −24.3%, −25.7% and −31.9% in the placebo and vericiguat 1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg groups, respectively; significance vs. placebo was observed in the vericiguat 10.0 mg group ( P = 0.035). Baseline‐adjusted mean percentage changes in SUA were 5.0%, −1.3%, −1.1%, −3.5% and −5.3% in the placebo, and vericiguat 1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg groups, respectively; significance vs. placebo was observed in the 5.0 mg and 10.0 mg groups ( P = 0.0202 and P = 0.004, respectively). Estimated probability for an end‐of‐treatment hsCRP value of ≤3.0 mg/L and SUA value of &lt;7.0 mg/dL was higher with vericiguat compared with placebo. The effect was dose‐dependent, with the greatest effect observed in the 10.0 mg group. Conclusions Vericiguat treatment for 12 weeks was associated with reductions in hsCRP and SUA, and a higher likelihood of achieving an hsCRP value of ≤3.0 mg/L and SUA value of &lt;7.0 mg/dL.
The complement component C5 is not responsible for the alternative pathway activity in rabbit erythrocyte hemolytic assays during eculizumab treatment
Authors: Lambertus P. van den Heuvel, Nicole C. A. J. van de Kar, Caroline Duineveld, Andrei Sarlea, Thea J. A. M. van der Velden, Wilhelmus T. B. Liebrand, Sanne van Kraaij, Camilla Schjalm, Romy Bouwmeester, Jack F. M. Wetzels, Tom E. Mollnes, Elena B. Volokhina
Journal: Cellular and Molecular Immunology (2020)
Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality
Authors: Robert O. Bonow, Gregg C. Fonarow, Patrick T. O’Gara, Clyde W. Yancy
Journal: JAMA Cardiology (2020)

Shaobo Shi, MD; Mu Qin, MD; Bo Shen, MD; Yuli Cai, MD; Tao Liu, MD; Fan Yang, MD; Wei Gong, MMSC; Xu Liu, MD, PhD; Jinjun Liang, MD, PhD; Qinyan Zhao, MD, PhD; He Huang, MD, PhD; Bo Yang, MD, PhD; Congxin Huang, MD, PhD
Abstract P2-14-05: Adjuvant chemotherapy in elderly women with triple-negative breast cancer: Swedish registry data 2009-2017
Authors: Slavica Janeva, Chenyang Zhang, Anikó Kovács, Toshima Z Parris, Anna-Karin Tzikas, Christopher M Pezzi, Riccardo A Audisio, Roger Olofsson Bagge
Journal: Cancer Research (2020)

Abstract Background: Breast cancer incidence is strongly related to age, with the highest incidence rates being in elderly women. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with worse survival. Due to competing mortality risks and co-morbidities, TNBC in the elderly is often under-treated with adjuvant chemotherapy. The aim of this study was to investigate if there is a gain in both breast cancer specific survival (BCSS) and overall survival (OS) with adjuvant chemotherapy in elderly patients with TNBC. Method: Information from all patients 70 years and older diagnosed with primary TNBC during the years 2009-2017 were retrieved from the Swedish National Register for Breast Cancer, the Swedish Cause of Death Register and the Swedish Patient Register. Both a propensity score matched (PSM) model and a Cox-regression model was created examining the effect of age, tumor size, tumor grade, nodal status, co-morbidities (Charlson/Deyo) and chemotherapy treatment, on BCSS and OS. Results: Of the 1421 patients included, 428 (30.1%) received chemotherapy. The 5-year BCSS was 84% vs. 62% in favor for patients receiving chemotherapy. The 5-year OS was 80% vs. 46% in favor for patients receiving chemotherapy. When adjusting for the co-variates using PSM, the 5-year BCSS was 84% vs. 73% (p&amp;lt;0.004) and the 5-year OS was 79% vs. 62% (p&amp;lt;0.001) favoring chemotherapy. Discussion: In this PSM registry analysis including all patients ≥70 years in Sweden with TNBC during a 9-year period, we could show that there was a significant benefit in both BCSS and OS with adjuvant chemotherapy when adjusting for both age and co-morbidities. Cox multivariate regression model for breast cancer specific survivalHazard Ratiop-value95% CIChemotherapy0.6020.0020.435-0.834Age (years)1.0510.0001.030-1.072Tumor size (mm)1.0170.0001.012-1.022Stage N11.9090.0001.488-2.450Stage N24.8550.0011.978-11.916Stage N31.9060.5210.266-13.637Grade 21.0140.9790.365-2.813Grade 31.6220.3400.601-4.374Charlson score1.1940.0570.995-1.433 Citation Format: Slavica Janeva, Chenyang Zhang, Anikó Kovács, Toshima Z Parris, Anna-Karin Tzikas, Christopher M Pezzi, Riccardo A Audisio, Roger Olofsson Bagge. Adjuvant chemotherapy in elderly women with triple-negative breast cancer: Swedish registry data 2009-2017 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-05.
Abstract P2-14-09: Results from a novel educational program to help nurses when discussing the Oncotype DX Breast Recurrence Score® with their patients
Authors: Lesley Fallowfield, Shirley May, Amanda Ramirez, Nina Fryer, Andrew Paramore, Valerie Jenkins
Journal: Cancer Research (2020)

Abstract Background Discussing risk of recurrence and potential treatment benefit in early breast cancer can be challenging, especially when dealing with anxious patients and/or those with difficult social circumstances. UK patients usually have access to specialist breast care nurses (SBCN) who discuss in further detail the implications that the Oncotype DX Breast Recurrence Score® result may have for:- treatment decisions, risks and benefits of chemotherapy and the potential impact on patients’ well-being and lifestyle. We developed an innovative communication skills workshop to assist SBCNs with these encounters. Methods The 6 hour workshops comprised:- 2 didactic presentations, one on the data underpinning the OncotypeDX® risk scores and cut-offs post TAILORx and another on the psychology of risk which included interactive exercises about numeracy, communication, and tolerance to uncertainty. Attendees then split into small groups for two practical sessions led by experienced facilitators. First they viewed one of 2 filmed scenarios of oncologists explaining Recurrence Score results with patients. The SBCNs then met with the same simulated patient just seen on film, who was now ‘in clinic’ a week later and keen to discuss her test result further. During these practical sessions facilitators engaged and encouraged the SBCNs to consider and practice different ways of handling the patients’ difficult questions. At completion of each session the simulated patients provided feedback and suggestions. Attendees completed 11 item pre/post workshop questionnaires probing their self-confidence when discussing complex issues surrounding the Recurrence Score® result. Results A total of 69 UK SBCNs participated. There were significant and positive improvements in mean change scores of self-rated confidence for all 11 issues, (P&amp;lt;0.004; Bonferonni) including handling discussions of scores post TAILORx. Workshops were rated as informative (9.6/10), useful (9.5/10) and enjoyable (9.6/10) with 68/69 (99%) recommending it to colleagues. Conclusion Nurses can play an important role helping patients’ decision-making; they are also usually fearful of role-play but most found the innovative practical sessions especially helpful. Our results showed that improved self-confidence, a key element required to lead to a transfer of communication skills into a clinic setting, was achieved in this six hour workshop. Citation Format: Lesley Fallowfield, Shirley May, Amanda Ramirez, Nina Fryer, Andrew Paramore, Valerie Jenkins. Results from a novel educational program to help nurses when discussing the Oncotype DX Breast Recurrence Score® with their patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-09.
The Role of the Household in Prescription Opioid Safety
Authors: Christopher M. Worsham, Michael L. Barnett
Journal: JAMA Network Open (2020)

Invited commentary:
Although the US has seen a decrease in opioid misuse rates among adolescents and young adults since 2015, opioid use disorder and overdose remain major public health problems in this high-risk population. Data from the US Substance Abuse and Mental Health Services Administration estimate that in 2018, 5.6% of young adults aged 18 to 25 years and 2.8% of adolescents aged 12 to 17 years misused prescription opioids in the past year.1 The reasons for high substance use rates in this age group are complex but include many factors rooted in neurodevelopment, socioeconomic characteristics, peer groups, and family life.........
Efficacy and safety of S-1 and gemcitabine in an unselected Western cohort of patients with unresectable pancreatic cancer.
Authors: Per Pfeiffer, Jon Kroll Bjerregaard, Katrine R. Schoennemann, Mathilde Korsgaard Weisz, Stine Brændegaard Winther, Helle Anita Jensen
Journal: Journal of Clinical Oncology (2015)

e15258 Background: Gemcitabine (Gem) has been the standard of care for untreated Caucasian patients (pts) with unresectable pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS1), however no data is published in Caucasian patients. In the present study we report our experience with a combination of GemS1 in an unselected cohort of Caucasian pts with PC. Methods: Patients with metastatic (mPC) and locally advanced PC (LAPC) were treated with Gem 1000 mg/m2 IV day 1+8 and S-1 25 mg/m2 BID days 1-14 every 3 weeks. In this observational cohort study, we analyzed all consecutive pts who had received at least one cycle of GemS1 at our department. Efficacy and toxicity were registered prospectively. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of S1 containing chemotherapy using the Kaplan-Meier method. Results: From July 2012 to July 2014, 64 pts received at least one course of GemS1. Forty-two pts had mPC and twenty-two LAPC. Sixteen pts started therapy with a combination of gem and capecitabine (GemCap) but switched to GemS1 after a median of 2.5 courses due to toxicity (HFS in all cases). In 48 pts the initial therapy was GemS1. Median age was 68 years (range 44-80); 16, 31 and 17 pts were in PS 0, 1, and 2, respectively. The most common adverse event was fatigue (84%), however only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 9.0 (95% CI: 6.9-11.0) months and the median OS was 11.7 (95% CI: 11.2-16.9) months. Conclusions: The combination of gemcitabine and S-1 is tolerable with promising efficacy in a Caucasian population with unresectable PC and should be evaluated in prospective clinical trials.
2017 American Academy of Pediatrics Clinical Practice Guideline: Impact on Prevalence of Arterial Hypertension in Children and Adolescents With Type 1 Diabetes
Authors: Axel Dost, Susanne Bechtold, Katharina Fink, Walter Bonfig, Dagobert Wiemann, Thomas M. Kapellen, Michael Witsch, Karl O. Schwab, Reinhard W. Holl
Journal: Diabetes Care (2020)

OBJECTIVE In 2017, the American Academy of Pediatrics introduced a new guideline (2017 Clinical Practice Guideline of the American Academy of Pediatrics [AAP 2017]) to diagnose arterial hypertension (HTN) in children that included revised, lower normative blood pressure (BP) values and cut points for diagnosing high BP in adolescents. We studied the impact of the new AAP 2017 on prevalence of HTN in children with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Up to September 2018, 1.4 million office BP measurements in 79,849 children and adolescents (aged 5–20 years) with T1DM were documented in the DPV (Diabetes Prospective Follow-up) registry. BP values of the most recent year were aggregated, and BP values of 74,677 patients without antihypertensive medication were analyzed (median age 16 years and diabetes duration 5.3 years, 52.8% boys). BP values were classified according to AAP 2017 and the references of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (2011) and the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (fourth report) (2004). RESULTS Of the patients, 44.1%, 29.5%, and 26.5% were hypertensive according to AAP 2017, KiGGS, and fourth report, respectively. Differences in prevalence of HTN were strongly age dependent: &amp;lt;10 years, AAP 2017 31.4%, KiGGS 30.7%, fourth report 19.6%; 10 to &amp;lt;15 years, AAP 2017 30.9%, KiGGS 31.2%, fourth report 22.4%; and ≥15 years, AAP 2017 53.2%, KiGGS 28.4%, fourth report 30.0%. Among teenagers ≥15 years, 59.1% of boys and only 46.3% of girls were classified as hypertensive by AAP 2017 but only 21.1%/26% of boys and 36.7%/34.4% of girls by KiGGS/fourth report, respectively. CONCLUSIONS Classification of BP as hypertension depends strongly on the normative data used. Use of AAP 2017 results in a significant increase in HTN in teenagers ≥15 years with T1DM, particularly in boys. AAP 2017 enhances the awareness of elevated BP in children, particularly in patients with increased risk for cardiovascular disease.
One- or two-stage laparoscopic right hemihepatectomy after portal vein embolization in patients with initially unresectable colorectal liver metastases: Technical aspects and clinical results
Authors: Burak Görgec, Amal Suhool, Ra’ed Al-jarrah, Martina Fontana, Nadeem Tehami, Sachin Modi, Mohammed Abu Hilal
Journal: International Journal of Surgery (2020)
マクロファージスカベンジャー受容体欠乏APOE3Leiden遺伝子組み換えマウスにおけるアテローム性動脈硬化の進行 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Dewinther Mpj, Gijbels Mjj, Vandijk Kw, Vangorp Pjj, Kodama T, Frants Rr, Havekes Lm, Hofker Mh
Journal: Circulation (1997)
The role of cancer-derived microRNAs in cancer immune escape
Authors: Ming Yi, Linping Xu, Ying Jiao, Suxia Luo, Anping Li, Kongming Wu
Journal: Journal of Hematology & Oncology (2020)

Abstract During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic cancer cells develop multiple strategies to evade immune attack. It has been well established that cancer cells could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway, and upregulate the activities of immune checkpoint pathways. Besides, cancer cells secret numerous cytokines, exosomes, and microvesicles to regulate the functions and abundances of components in the tumor microenvironment including immune effector cells and professional antigen presentation cells. As the vital determinant of post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer initiation and progression but also regulate anti-cancer immune response. For instance, some miRNAs affect cancer immune surveillance and immune escape by interfering the expression of immune attack-associated molecules. A growing body of evidence indicated that cancer-derived immune modulatory miRNAs might be promising targets to counteract cancer immune escape. In this review, we summarized the role of some miRNAs in cancer immune escape and discussed their potential clinical application as treatment targets.
The results of portal vein resection and reconstruction for treatment of Klatskin tumor
Authors: Oleg Kotenko, Oleg Popov, Oleksander Korshak, Oleksander Grinenko, Denis Fedorov, Andrii Husiev, Marat Grigorjan, Oleksander Ostapishen, Andrii Zhylenko
Journal: International Journal of Surgery (2020)
Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study)
Authors: Adam R. Glassman, John A. Wells, Kristin Josic, Maureen G. Maguire, Andrew N. Antoszyk, Carl Baker, Wesley T. Beaulieu, Michael J. Elman, Lee M. Jampol, Jennifer K. Sun
Journal: Ophthalmology (2020)
Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors
Authors: Junji Tsurutani, Hiroji Iwata, Ian Krop, Pasi A. Jänne, Toshihiko Doi, Shunji Takahashi, Haeseong Park, Charles Redfern, Kenji Tamura, Trisha M. Wise-Draper, Kaku Saito, Masahiro Sugihara, Jasmeet Singh, Takahiro Jikoh, Gilles Gallant, Bob T. Li
Journal: Cancer Discovery (2020)

HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8-11.1] months. In HER2-mutant non-small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1-14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGNIFICANCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or HER2-mutant solid tumors, especially HER2-mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention. Further research of T-DXd is warranted to address these unmet medical needs.See related commentary by Rolfo and Russo, p. 643.This article is highlighted in the In This Issue feature, p. 627.
Abstract P2-18-09: Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials
Authors: Henrique AV Träsel, Frederico S Falcetta, Fernando K Almeida, Mariana RR Falcetta, Daniela D Rosa
Journal: Cancer Research (2020)

Abstract Purpose: Randomized clinical trials are inconclusive regarding the role of dietary interventions in anthropometric measurements, quality of life, and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women who went through curative treatment of early-stage breast cancer.Methods: Pubmed, Embase, Cochrane Library were searched for randomized clinical trial comparing dietary interventions (individualized dietary counseling, prescription of a specific diet or other) with usual care in women that were treated for breast cancer. Primary outcomes were overall survival and disease-free survival, secondary outcomes were weight loss and change in body mass index.Results: We found 12 clinical trials eligible for analysis. Only two of them reported overall and disease-free survival, whereas six reported data for body mass index and four for weight. The HR for mortality and disease-free survival was 0.91 (95% CI 0.77-1,07, p=0.25) and 0.92 (CI 95% 0.79-1.08, p=0.31) for the intervention group compared to the control group, respectively. Diet intervention was associated with body mass index reduction in those subjects who received a specific diet instead of counseling or other types of intervention (-0.67 CI 95% -1.14 to -0.21). The weight did not differ between intervention and control groups.Conclusions: Despite increasing survival among breast cancer patients there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measure, but neither difference in overall nor disease-free survival. Citation Format: Henrique AV Träsel, Frederico S Falcetta, Fernando K Almeida, Mariana RR Falcetta, Daniela D Rosa. Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-09.
Offering Avastin for wet AMD is legal, says appeal court
Authors: Clare Dyer
Journal: BMJ (2020)

The Court of Appeal has ruled unanimously that a policy of offering bevacizumab (Avastin) off label to NHS patients with wet age-related macular degeneration (AMD) as an alternative to the much more expensive drugs ranibizumab (Lucentis) and aflibercept (Eylea) is lawful.1

In a major judgment with far reaching implications for the NHS and the drug industry, the three judges rejected arguments by the drug companies Novartis and Bayer that the policy breached EU law on medicines and UK legislation.

Twelve clinical commissioning groups in the north of England adopted a policy in 2017 that the NHS trusts providing services to them should offer patients a choice between bevacizumab, licensed as a cancer treatment but not …