tbuckley/cabot-search huggingface dataset:
Stability and visual compatibility of daunorubicin and cytarabine during Y-site administration with selected drugs.
Authors: Guillaume Sicard, Mélanie Donnette, Bertrand Pourroy, Raphaëlle Fanciullino
Journal: Journal of Clinical Oncology (2020)

e15516 Background: Vyxeos is a daunorubicine plus cytarabine liposome indicated in adults patient with newly diagnosed acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and therapy-related AML (t-AML). The standard protocol is an induction phase on D1, D3 and D5 at 100 mg/m² (expressed in cytarabine) during 90 minutes followed by 2 consolidation cures at 65 mg/m² on D1 and D3. Data provided from manufacturer indicate stability over 4 hours for diluted solution of daunorubicine plus cytarabine. AML-Patients are all receiving complex infusion increasing the risk of Y site incompatibilities. However, there is a lack of data on Y site compatibility of daunorubicine plus cytarabine with others drugs while these phenomena are well described with cytarabine and daunorubicine. The aim of this study was to evaluate stability and container-content interaction over time and visual Y site compatibility with selected drugs. Methods: Physicochemical stability over time was evaluated by Dynamic Light Scattering (DLS) (particle size) and by LC-MS/MS analysis (determination of cytarabine concentration). Daunorubicine plus cytarabine diluted solutions in 0.9% NaCl, final concentration 0.17 mg/mL were stored at 4°C during this study. Container-content interaction was evaluated comparing glass bottle and free-PolyVinylChloride (PVC) bag. Regarding Y site compatibility, a total of 33 drugs were tested. Medication mixtures were analyzed immediately after contact (T=0) and 90 minutes after, stored at room temperature (i.e., 25°C). The particle analyses were performed visually and by DLS. Drugs couple were classified in three categories: compatible, incompatible and variable compatibility when dubious phenomenon was observed. Results: No significative difference was found over time (120h) in term of particle size and chemical stability of cytarabine encapsulated, regardless of the container. This suggests that stability of daunorubicine plus cytarabine could actually be much longer than manufacturer’s recommendations. Most of the tested drugs were compatible. Still, three drugs exhibited visual incompatibilities at T = 0 and T = 90 minutes. However seven drugs presented incompatibilities using LDS. Two combinations presented conflicting data and thus classified as variable compatibility. Conclusions: Polypharmacy is a major concern in AML patients and knowledge and management of daunorubicine plus cytarabine stability and Y site compatibilities are critical to ensure a maximum safety at bedside. At least 10 drugs frequently used in oncology present a variety of incompatibilities with daunorubicine plus cytarabine and therefore should not be co-administered on Y site.
Deregulated expression of the imprinted <i>DLK1-DIO3</i> region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3
Authors: Mariachiara Buccarelli, Valentina Lulli, Alessandro Giuliani, Michele Signore, Maurizio Martini, Quintino G D’Alessandris, Stefano Giannetti, Agnese Novelli, Ramona Ilari, Giorgio Giurato, Alessandra Boe, Giorgia Castellani, Serena Spartano, Giuseppe Marangi, Mauro Biffoni, Maurizio Genuardi, Roberto Pallini, Giovanna Marziali, Lucia Ricci-Vitiani
Journal: Neuro-Oncology (2020)

Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene‒type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis.Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3).Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT).In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies.
她的血压怎么了
Authors: 徐宝华, 谢立群, 王及华
Journal: BMJ (2011)

2009年在一家医院心内科进修时遇到一位顽固性高血压患者,辗转求医二十几年未能控制血压. 患者女性,46岁,发现血压升高25年,血压一直波动于180～260/120～130 mm Hg(1 mm Hg=0.133 kPa),自服复方利血平片,效差.21年前曾疑诊左肾上腺嗜铬细胞瘤,予左肾上腺切除,病理学检查示左肾上腺结节性增生.但术后血压仍无明显缓解。
医源性泌尿系损伤14例临床分析
Authors: 陈林, 昌建明, 刘晨波, 吕建阳
Journal: BMJ (2010)

医源性泌尿系损伤虽然在泌尿系损伤中只占少数,但严重的可能给患者造成很大的伤害和痛苦或并发一些并发症,甚至造成器官功能不全.提高对医源性泌尿系损伤认识可减少其发生.我科从1994年至2009年,接诊处理本院和外院发生医源性泌尿系损伤患者14例,现报道如下。
脑性瘫痪的社区康复指导
Authors: 李晓捷, 吕智海
Journal: BMJ (2012)

脑性瘫痪是导致我国儿童肢体残疾的主要疾病之一,目前康复需求量占儿童康复的首位.由于我国人口众多,各地社会发展及医疗资源尚不均衡,集中式康复难以解决广大患儿长期康复需求.本文力争以简捷、易懂、易操作的方式简要介绍脑性瘫痪的基本概念及社区康复的相关内容,以供社区康复工作者、患儿家长及有关人员参考应用。
Survival outcomes in post-menopausal patients with underlying cardiovascular disease receiving endocrine therapy for the treatment of breast cancer.
Authors: Priyanka Parajuli, Odalys Estefania Lara Garcia, Ruby Maini, Manjari Rani Regmi, Nitin Tandan, Noupama Mirihagalle, Asad Cheema, Sabree Abedrabo, Zurain Niaz, Cameron Koester, Hamsa Sahib, Bishal Bhandari, Alexander Johnson, Abdisamad M. Ibrahim, Kristin Delfino, Kathy Robinson, Meghna R. Desai, Abhishek Kulkarni
Journal: Journal of Clinical Oncology (2020)

e12549 Background: Breast cancer remains the number one threat to women’s health while cardiovascular disease (CVD) continues to be the leading cause of mortality in women worldwide. Adjuvant therapy with endocrine therapies (selective estrogen receptor modulators (SERM), estrogen receptor blockers (ERB), and aromatase inhibitors (AI) although known to reduce the recurrence of breast cancer in hormone receptor positive breast cancer patients, raise a concern for increased risk of cardiovascular disease. Our study aims to examine breast cancer survival outcomes on patients receiving endocrine therapy who have pre-existing CVD including heart failure. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Preexisting CVD included coronary artery disease (CAD), history of myocardial infarction (MI), and prior diagnosis of heart failure (HF). Patients were divided in groups depending on treatment with endocrine therapy and underlying CVD. Statistical analysis was performed with SAS v9.4. software. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance was assumed at the p &lt; 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Out of those 336 patients, 62.2 % (n = 209) received at least one of the endocrine therapies consisting of AI, SERM or an ERB. Of these patients, 2.9 % (n = 6), 9.6% (n = 20) and 5.7% (n = 12) had a significant medical history of underlying MI, HF and CAD, respectively. Survival analysis was performed on 80% (n = 168) patients of the 209 patients with 2.3% (n = 4), 8.9% (n = 15) and 5.2% (n = 11) with underlying MI, HF and CAD respectively. There was no statistically significant difference in survival in these postmenopausal women who received endocrine therapy despite preexisting cardiovascular disease (HR 3; 95% CI, 0.5-16, p &gt; 0.05). Conclusions: A commonly known toxicity related to the adjuvant therapy including endocrine therapy of breast cancer is cardiac toxicity. Patients with history of CVD might be at the highest risk for such toxicity. Our finding is reassuring that endocrine therapy in patients with preexisting CVD including heart failure did not result in reduced survival for our patient cohort.
Once-only flexible sigmoidoscopy screening for adults aged 55-64 years old reduces the incidence of colorectal cancer and colorectal cancer deaths
Authors: Blom Johannes, 卫茂玲, 王一平
Journal: BMJ (2011)

内容结直肠癌因其发病率和死亡率均高已成为一个重要的健康问题，但理想的筛查方法发现，早期癌是可以治愈的。粪便隐血试验筛查证实可减少结肠直肠癌死亡率，且已被用于欧洲数个筛查项目。此外，筛查项目和纤维乙状结肠镜使用，通过去除癌前病变——腺瘤性息肉，对降低结直肠癌的发生率也具有潜在价值。
The landscape of gastrointestinal oncologic phase III clinical trials in the last two decades.
Authors: Joseph Abi Jaoude, Ramez Kouzy, Walker Mainwaring, Timothy Lin, Austin B. Miller, Amit Jethanandani, Andres F. Espinoza, Ethan B. Ludmir, Cullen M. Taniguchi
Journal: Journal of Clinical Oncology (2020)

e14087 Background: Gastrointestinal (GI) cancers are among the most common cancers in adult patients. The prognosis of GI cancers differs widely between specific subsites, with some cancers having excellent prognoses, and others (such as pancreatic and hepatobiliary cancers) having an extremely poor prognosis. We sought to characterize the landscape of GI oncologic clinical trials in the last two decades. Methods: We searched ClinicalTrials.gov for phase III RCTs between 2003 and 2018. Randomized multi-arm trials assessing a therapeutic intervention in adult cancer patients were included. GI cancer trials were identified and grouped into specific disease subsites. Differences in trial factors between GI and non-GI trials and between different GI subsites were analyzed. Results: Out of the 600 RCTs identified, 76 trials assessed gastrointestinal cancers (12.7%). By disease subsite, we identified 21 (27.6%) gastro-esophageal cancer trials, 12 (15.8%) pancreatic cancer trials, 11 (14.5%) hepatobiliary cancer trials, and 32 (42.1%) colorectal cancer trials. GI cancer trials were more likely to be industry funded when compared to non-GI cancer trials (88.2% vs 76.3% respectively, p = 0.02). Furthermore, only 18.4% of GI trials had cooperative group sponsorship (vs 33.3% for non-GI trials, p = 0.01). Most GI cancer trials assessed systemic therapy interventions (85.5%); only 6 trials (7.9%) addressed supportive care interventions (vs 20.2% for non-GI trials, p = 0.01). Around half of GI cancer trials (51.3%) met their primary endpoints, but only 8 trials (10.5%) led to subsequent FDA approval. All FDA approvals were for colorectal cancer treatments, and none for gastroesophageal, pancreatic or hepatobiliary cancers (p = 0.01). Most patients (97.1%) accrued on GI cancer trials had a good performance status (Eastern Cooperative Oncology Group of 0 to 1). Specifically, 95.9% of patients in pancreatic trials and 98.6% of patients in hepatobiliary trials had a good performance status. Conclusions: While many GI cancers have a poor prognosis, very few trials assess supportive care interventions in this populations. Moreover, most patients included in GI cancer trials have a good performance status. In that regard, future GI cancer trials addressing supportive care measures with a wider cancer population are still warranted.
Lack of evidence to support large-panel genomic testing in treatment selection for malignant melanoma.
Authors: Maya Dimitrova, Min Jae Kim, Douglas M. Donnelly, Keith M. Giles, Una Moran, Jeffrey S. Weber, Iman Osman, George Jour
Journal: Journal of Clinical Oncology (2020)

e22027 Background: Genomic profiling informs clinical decision-making for malignant melanoma (MM) as specific tumor mutations can be treated with targeted therapy (TT). However, given the range of different panel sizes available and increasing use of immune checkpoint inhibitors (ICI), the clinical significance of upfront, large-panel genomic profiling in MM remains undetermined. Herein, we investigate the impact of panel size and targetable mutational status on first-line treatment selection and outcomes of MM patients from 9 different institutions. Methods: We analyzed data for 1,341 MM patients from 3 cohorts. Cohort 1 included 169 patients enrolled at NYULH and profiled with the 50 gene Ion Torrent panel (IT). Cohort 2 included 256 patients enrolled at MSKCC, profiled with the 400-gene MSK-IMPACT panel (MSK-I). Cohort 3 included 916 patients enrolled at 7 different sites, profiled with whole exome sequencing (WES). Data for cohorts 2 and 3 were extrapolated from publicly available data using cBioPortal. We tested associations between molecular data, treatment choice and overall survival (OS), adjusting for baseline characteristics when available. Results: Treatment information was available for 100%, 25%, and 0% of patients in cohort 1, 2 and 3, respectively. Stage was available for all of cohort 1 (III, n = 68; IV, n = 101) and cohort 2 (III, n = 2; IV, n = 254), but in only 23% of cohort 3 (III, n = 184; IV n = 25). For the IT and MSK-I, BRAF and NRAS were among the top 5 most commonly mutated genes, whereas for WES only BRAF was in the top 5. In cohort 1, 36% (16/45) of BRAF MUT patients received first-line TT vs 25% (66/256) in cohort 2. There was no significant difference for BRAF MUT patients treated with ICI vs. TT in cohort 1 in OS (P = 0.19), nor for BRAF MUT patients from cohort 1 treated with ICI vs. those from cohort 2 treated with TT (OS P = 0.762). Conclusions: Publicly available datasets provide population-level data, however the heterogeneity and deficiency of reported clinical information limits their value and calls for data standardization. Without evidence of clear clinical benefit of a larger panel size, there is a rationale for adopting smaller, more cost effective panels in MM.
Present-day management of uterine leiomyosarcoma: Evaluation of treatment sequencing and other prognostic factors.
Authors: Emily Hinchcliff, Jennifer Rumpf, Ravin Ratan, Nicole D. Fleming, Amir A. Jazaeri, Brandelyn Pitcher, Pamela T. Soliman
Journal: Journal of Clinical Oncology (2020)

e18035 Background: Uterine leiomyosarcoma (ULMS) is a rare tumor with limited therapeutic options and no clearly established best treatment sequence strategy. Methods: Women with ULMS between 2013-2018 were identified. Clinical data was collected; descriptive statistics were performed and predictors of overall survival (OS) and progression free survival (PFS) were analyzed. Results: 189 patients were included. Median age was 53 (20-84), 91% had grade 3 tumors and 51.3% had stage IB disease. 50% underwent surgery followed by chemotherapy (n = 94, 49.7%) and 37% had surgery only (n = 70). 49 patients retained their ovaries; there was no difference in OS by oophorectomy status (p = 0.71). Estrogen and progesterone receptor (ER/PR) status, positive in 41% and 33% respectively, was not independently associated with OS (p = 0.23, p = 0.12) nor did it impact OS among those with oophorectomy and without (p = 0.70). The most common adjuvant therapy regimens were gemcitabine/docetaxel (gem/doce, 64%) or ifosphamide/doxorubicin (ifos/doxo, 19%). There were no differences in the regimens prescribed by physician specialty (gynecologic oncology vs other, p = 0.21). 147 patients (78%) experienced a recurrence or progression. For the 73 patients who received gem/doce as adjuvant therapy, 58.9% recurred and were most commonly treated with doxo containing regimens (67%). Of the 22 patients treated with ifos/doxo, only 3 recurred and each received a different second line regimen. For those not treated with adjuvant therapy (70 patients), 58.2% recurred and were treated with gem/doce (62%) and ifos/doxo (24%). In early stage patients, the majority received surgery only (45%) or surgery followed by chemotherapy (44%). There was no difference in OS in those who received adjuvant therapy and those who did not (p = 0.39). 46 (24%) had molecular testing and 37 had identified mutations. The most common mutation found was P53 (n = 25, 54%) followed by RB1 (8, 17%), PTEN (7, 15%), and BRCA (2, 4%). Conclusions: Recurrence occurred in 78% of patient despite many women undergoing adjuvant therapy after surgery. Oophorectomy did not influence OS, even though 41% of tumors were ER positive. The sequence of treatment was not associated with OS, however, the risk for recurrence in patient treated with adjuvant Ifos/Doxo was 14% compared to 59% in gem/doce. This finding warrants additional evaluation to determine the optimal adjuvant therapy for these women.
Mantle cell lymphoma: initial report from the North American Mantle Cell Lymphoma Consortium.
Authors: Kai Fu, Guohua Yu, Chengfeng Bi, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad, Brian K. Link, Craig R. Nichols, Paul M. Barr, Brad S. Kahl, Douglas Stewart, Stefan K Barta, Anne Beaven, Ranjana H. Advani, Peter Martin, Timothy Greiner, Dennis Weisenburger, James O. Armitage, Julie Vose
Journal: Journal of Clinical Oncology (2020)

8035 Background: The goal of the North American Mantle Cell Lymphoma (MCL) Project is to evaluate the clinical, biological, and genomic markers that affect the outcome of patients with MCL. Methods: We have retrospectively studied the clinical and pathological features of 307/421 patients diagnosed with MCL between January 2000 to December 2012 from 23 institutions across North American. Results: The male to female ratio of MCL patients was 3.5:1, with a median age of 66 years (range: 24-106 years). Approximately 29% of patients (78/269) presented with B symptoms and 257 (257/307, 83.7%) patients had extranodal involvement at diagnosis. Median follow-up was 7.1 years (range, 0.03 to 16.6 years) with the five-year PFS and OS at 27.8%, and 54.4%, respectively. Univariate analysis revealed that the following factors were significantly associated with both inferior OS and PFS ( p&lt; 0.05): older age (≥60 years), presence of B symptoms, advanced Ann Arbor stage, elevated LDH, low platelets (≤100K/ml), blastoid/pleomorphic cytology, Ki67 proliferation ≥30%, circulating tumor cells, no transplantation (vs. transplantation), and allogeneic (vs. autologous) stem cell transplantation. In addition, large tumor size (maximal diameter &gt; 3cm), high WBC ( &gt; 10×10 3 /ml), CD5 or CD23 positivity, and a complex karyotype were associated with inferior OS ( p&lt; 0.05). Multivariate Cox regression analysis showed age (≥ 60y; p= 0.0028, HR = 2.44, 95% CI: 1.36-4.38) and high LDH ( p= 0.0062, HR = 2.19, 95% CI: 1.25-3.84) were the two factors predicting the clinical outcome. MIPI-c, a commonly used prognostic scoring system which includes Ki67, stratified the 100 MCL cases into four group with distinct clinical outcomes ( p&lt; 0.001). Using readily-available clinical and pathological variables, we developed a simple and robust scoring system, MIPI-P (pathology), which consisted of age (≥60 years), LDH (high), Ki67 index (≥30%), Ann Arbor stage (III/IV), and cytological type (blastoid/pleomorphic), each contributing one point. The MIPI-P system stratified 104 MCL cases into three distinct groups ( p&lt; 0.001). Median survival for the different groups were: low grade (0-1 points): 11.8 years; intermediate grade (2-3 points): 4.9 years; and high grade (4-5 points): 1.6 years. We further validated this system in an independent cohort of 33 MCL cases and confirmed that the modified MIPI-P provided robust prognostic predication ( p= 0.014). Conclusions: The clinical and biologic characteristics of MCL can provide information assisting with the prognosis of patients with MCL.
Abstract 14713: Coronary Dominance and Risk of Ventricular Fibrillation in Coronary Artery Disease
Authors: Kumar Narayanan, Audrey Uy-Evanado, Carmen Teodorescu, Kyndaron Reinier, Harpriya Chugh, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2015)

Introduction: Recent studies have suggested a link between coronary dominance and overall prognosis in patients with coronary artery disease (CAD). A specific association with sudden cardiac arrest (SCA) has not been investigated. Hypothesis: Coronary dominance pattern is associated with SCA risk. Methods: From a large, prospective, population-based study of SCA in a Northwestern US metro region (approx. one million residents), we identified SCA cases who underwent coronary angiogram at cardiac arrest and compared the coronary dominance pattern to a geographically-matched control population without history of SCA, undergoing angiograms for acute coronary syndromes (ACS) over the same time period. Results: Angiographic data were compared between a total of 203 SCA cases and 173 control subjects. Cases and controls respectively were not significantly different in age (62.3± 12.4 vs 64.3 ± 10.9 years; p=0.09), sex (males 69.8% vs 71.7%, p=0.69), body mass index (29.0 ± 7.7 vs 29.1 ± 6.6; p=0.89), diabetes (33.5% vs 27.9%; p=0.24), hypertension (62.5% vs 65.7%; p=0.52) and previous history of myocardial infarction (36.0% vs 34.9%; p=0.82) or coronary revascularization (18.7% vs 25.4%; p=0.12). Ventricular tachycardia or fibrillation (VT/VF) was the presenting arrest rhythm in the majority (86.9%) of cases. Compared to controls, a right dominant coronary system was less likely to be seen in cases (78.4% vs 86.7%) and a co-dominant system was more likely to be present (9.9% vs 1.9%) with nearly equal left dominance (11.7% vs 11.4%) (p for between group comparisons = 0.04). A co-dominant system was associated with an increased odds of SCD [OR 5.6 (1.2-26.2); p=0.01].There was no difference in the proportion of cases and controls with significant stenosis (≥ 50%) in the posterior descending artery (4.4% vs 8.7%; p=0.10). Conclusions: In this community-based study, we identified specific patterns of coronary dominance associated with VF. Mechanisms related to the area of myocardium at risk or vascular supply to the inferior (vagal) surface of the heart may be involved and warrant further focused evaluation.