tbuckley/cabot-search huggingface dataset:
Preliminary results from CAMEO-PRO study: Complementary and alternative medicine in oncology—Physicians inform oncological patients.
Authors: Claudia Bozza, Lorenzo Gerratana, Debora Basile, Maria Grazia Vitale, Michele Bartoletti, Elisa Agostinetto, Stefania Russo, Marta Bonotto, Marika Cinausero, Valentina Fanotto, Giacomo Pelizzari, Camilla Lisanti, Alessandro Marco Minisini, Claudia Andreetta, Mauro Mansutti, Elena Poletto, Donatella Iacono, Roberta Sottile, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2017)

e21632 Background: It is estimated that about half of cancer patients (pts) use at least one form of (CAM) Complementary and Alternative Medicine in their life but there is a strong reticence of pts in talking about CAM with their oncologist. Aim of this study is to inform pts about CAM. Methods:From April to December 2016, the observational pilot trial “CAMEO-PRO” prospectively enrolled 200 cancer pts that were invited to attend a tutorial about CAM at the Department of Oncology, University Hospital of Udine (Italy). Before and after the seminar, pts were asked to fill a questionnaire reporting their knowledge and opinion about CAM . Results:Median age was 61 years, 141 (72%) women and 53 (28%) men. At study entry, 139 (72%) pts declared they have never been interested in this topic before; 22 pts (12%) revealed the use of a type of alternative therapy and 53 (31%) revealed the use of complementary therapy. Overall, 111 (55.5%) pts participated to the tutorial. Table 1 shows the percentage of response and the opinion’s change about CAM before and after the tutorial. Conclusions:Informative seminars seem to have an impact on patients’ perceptions and opinions about CAM. [Table: see text]
Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents
Authors: Yoshitaka Ito, Kazuhiro Naito, Katsuhisa Waseda, Hiroaki Takashima, Akiyoshi Kurita, Hirohiko Ando, Kazuyuki Maeda, Shinichiro Sakurai, Akihiro Suzuki, Yuki Saka, Tomofumi Mizuno, Isao Kato, Yasushi Suzuki, Tetsuya Amano
Journal: Circulation (2015)

Background: While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT. Methods: A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score&lt;4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion. Results: Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score. Conclusion: High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.
Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I): An ACCRU trial.
Authors: Kathryn Jean Ruddy, Jennifer Le-Rademacher, Mario E. Lacouture, Mary Wilkinson, Adedayo A. Onitilo, Amy C. Vander Woude, Maria T. Grosse Perdekamp, Travis Dockter, Angelina D. Tan, Andreas S. Beutler, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2018)

e22075 Background: Cooling the extremities during chemotherapy has been hypothesized to reduce subsequent peripheral neuropathy. Methods: A randomized pilot trial was conducted comparing cryotherapy to standard care (control) in patients initiating paclitaxel weekly for 12 weeks to inform the development of a phase III trial. For those on the cryotherapy arm, the hands and feet were cooled starting 15 minutes prior to each paclitaxel dose and for 15 minutes after each dose was complete. Questionnaires, including EORTC QLQ-CIPN20, were completed at baseline and weekly through the end of paclitaxel. The EORTC QLQ-CIPN20 subscale scores were summarized and plotted by treatment arm. The area under the curve (AUC) was calculated using the trapezoidal rule after adjusting for baseline score and compared between arms, using the Wilcoxon rank-sum test. Cross-study comparisons were performed using data from two prior similarly-conducted clinical trials. Results: Forty-six patients were accrued, three of whom withdrew and one of whom was ineligible. Of the remaining 42 (21 cryotherapy, 21 control), 39 (19 cryotherapy, 20 control) were analyzable for AUC based on availability of both baseline and follow-up measures. The cryotherapy was reasonably well tolerated, with 16 cryotherapy and 17 control arm patients completing study therapy. EORTC QLQ-CIPN20 data did not reveal significant differences between the 2 study arms in any neuropathy outcome. However, patients in the control arm of the current trial experienced substantially less neuropathy than did those in the placebo arms of two similar trials that assessed minocycline and pregabalin in this setting. When the cryotherapy arm of the current trial was compared to the combined control arms from all three trials, it appeared that there was less neuropathy in this cryotherapy arm than the combined control arms (Wilcoxon Rank Sum p = 0.004). Conclusions: While there was no difference in CIPN20 scores between the study arms in the current trial, further investigation is needed given that this control arm did unexpectedly well. Clinical trial information: NCT02640053.
Abstract 19605: Identification of M1 Macrophages in Vulnerable Plaques With Folate Receptor Beta Targeted Liposomal Indocyanine Green J-Aggregates
Authors: Justin T Harris, Diego S Dumani, Jason R Cook, Konstantin V Sokolov, Stanislav Y Emelianov, Kimberly A Homan
Journal: Circulation (2016)

In the US alone, approximately 500,000 deaths per year result from the rupture of plaques considered “insignificant” upon angiographic evaluation. These “vulnerable plaques” are characterized by a ...
Endoscopic gastrojejunostomy – bigger is better
Authors: Luai Madanat, Monica Saumoy, Reem Sharaiha
Journal: Endoscopy (2018)

A 55-year-old man with a history of multiple gunshot wounds complicated by dense adhesions from several previous episodes of abdominal surgery presented with persistent nausea/vomiting. His past medical history included a chronic enterocutaneous fistula, which had been closed with an atrial septal occluder. Additionally, he had had vomiting due to a duodenal stricture secondary to adhesions and he had undergone endoscopic ultrasound (EUS)-guided gastrojejunostomy with a lumen-apposing metal stent (LAMS). This had been complicated by stent misdeployment that required placement of a second tandem LAMS. The patient had reported improvement in his quality of life after closure of the enterocutaneous fistula and weight gain after undergoing the gastrojejunostomy. However, 6 months later, he developed recurrent nausea/vomiting.
Minimally-invasive dual testing for active HPV E6,E7 and PD-L1 expression in HNSCC.
Authors: Haitham Mirghani, Yvette Carrasco, Amanda Chargin, Bruce Kendrick Patterson
Journal: Journal of Clinical Oncology (2018)

6064 Background: Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) have better prognosis when HPV associated or with a positive PD-L1 status. The often invasive nature of testing as well as the turnaround time for results are impactful on the doctor-patient relationship as available testing influences level of care. This assay was performed with minimally invasive swabs of lesions from HNSCC patients. Non-subjective and quantitative results for E6,E7 mRNA overexpression as well as PD-L1 expression in these tumors were obtained by a three color flow cytometry assay. Methods: Swabs from patients with oropharynx lesions at the Institut Gustave Roussy were fixed with a proprietary solution (IncellMAX, IncellDx) and sent for processing. Received samples were strained through a 35 uM filter, underwent ISH with E6, E7 mRNA probes (HPV OncoTect, IncellDx), stained with a PD-L1 Antibody (28-8), and stained with a cell cycle dye to verify cells. Stained samples were analyzed by flow cytometry. Institut Gustave Roussy provided FFPE lesion biopsy tissue collected from the same area of swab collection. Slides from FFPE lesion biopsy tissue were processed by Gustave Roussy with p16 IHC. Positive p16 results were confirmed by HPV gDNA ISH (Inform HPV III, Ventana). Slides were also processed by Bioreference Laboratories for PD-L1 expression by IHC (PD-L1 IHC 28-8 pharmDx, Agilent). Results: Oral pharynx swab samples from 40 unique patients with HNSCC were tested by flow cytometry for E6,E7 and PD-L1 overexpression. Results were compared to p16/ISH and PD-L1 IHC results from the tumor biopsy. Initial analysis of 30 samples show concordance of 73.3% between E6,E7 over expression by flow cytometry and p16 by IHC. [Additional data to be presented at the conference, currently pending PD-L1 IHC results]. Conclusions: Providing quantification of HPV E6, E7 mRNA and PD-L1 expression through a minimally invasive method presents a profound ability for clinicians to decide treatment options for patients. Ease of sampling coupled with the ability to both multiplex targets and scale-up the assay provides great possibility in treatment in disease.
Abstract 287: Metabolic Control of Ischemic Cardiac Injury in Human Cardiomyocytes
Authors: Dongjian Hu, Nikita Shah, Ibrahim J Domian
Journal: Circulation Research (2017)

Acute myocardial infarction is a leading cause of cardiac dysfunction and heart failure. As a result, developing in vitro models of myocardial ischemia has been important for the elucidation of the mechanisms of hypoxic injury and the development of novel cardioprotective strategies. During acute ischemia, cardiac injury occurs in minutes to hours in vivo but in hours to days in vitro. This difference in response to ischemia is compounded by differences in cardiomyocytes’ (CMs) metabolism and substrate utilization under standard in vitro growth conditions. An important challenge in modeling ischemia has been to faithfully recapitulate the in vivo cellular response to hypoxic stress. To address this limitation, we have performed comprehensive phenotypic characterization of myocardial metabolism and contractile functions in vitro during normoxia and hypoxia under different metabolic conditions. We show that, unlike CMs in the adult heart, adult murine CMs and hPSC-CMs cultured in glucose as the primary energy source utilize aerobic glycolysis and not oxidative phosphorylation (OXPHOS) for ATP generation. In contrast, CMs cultured with fatty acids as the primary energy source are dependent on OXPHOS for ATP generation and contractile function. Consistent with these findings, only CMs cultured in fatty acid have an acute drop in ATP production and contractility in response to hypoxia. We then show that by modulating the transcriptional activity of hypoxia-inducible factor 1-alpha, its upstream regulator sirtuin, and its downstream target lactate dehydrogenase A, CMs cultured in glucose shift their metabolism from glycolysis to the more metabolically appropriate OXPHOS. Collectively, our results provide novel mechanistic insights into the key regulatory pathways that control hPSC-CMs’ energy metabolism and highlight the significance of comprehensive characterization of CMs’ metabolic and functional responses to ischemic stress in vitro. By creating in vitro models of ischemic injury that can faithfully recapitulate cellular responses of myocardial infarction, it is then possible to identify relevant therapeutic targets for the treatment the disease.
Subgroup analysis of histology in ALTER0303: Anlotinib hydrochloride as 3rd line and further line treatment in refractory advanced NSCLC patients (pts).
Authors: Ying Cheng, Baohui Han, Kai Li, Qiming Wang, Li Zhang, Jianhua Shi, Zhehai Wang, Jianxing He, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin, Baolan Li
Journal: Journal of Clinical Oncology (2018)

9080 Background: In the ALTER0303 trial (NCT02388919), anlotinib hydrochloride was used as subsequence therapy for adult IIIB/IV NSCLC pts who progressed after at least 2 lines of prior systemic therapies. It has demonstrated that anlotinib significantly prolonged OS and PFS in advanced NSCLC pts as 3rd line treatment. Here we report the efficacy of anlotinib in pts with different histology, including adenocarcinoma (ACC), squamous cell carcinoma (SCC) and so on. Methods: 437 pts were randomised in a 2:1 ratio to receive anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) or placebo till progression or intolerable toxicity. Pts harboring EGFR or ALK mutations must had received previously targeted therapies. Primary endpoint is OS. Histology was the pre-stratified factor. Results: For the ACC pts (n=336), PFS and OS were both significantly improved in the anlotinib arm, and the most common grade ≥3 treatment-related AEs were hypertension and hypertriglyceridemia. Furthermore, in the subgroup of pts with SCC (n=76), remarkable advantages in PFS were observed in the anlotinib arm as well. Hypertension, hyponatremia and hemoptysis were the most common AEs in SCC NSCLC. (Data presented in the Table) Conclusions: In the ALTER0303 trial, a significant improvement in PFS was found in anlotinib treated pts from both subgroups (ACC and SCC). This is indicating that using anlotinib as subsequence therapy strategy not only led to the improvement in OS and PFS for advanced ACC pts, but also prolonged PFS of the SCC pts. Anlotinib could be an appropriate option for this difficult-to-treat NSCLC pts as subsequence treatment regardless of the histology. Clinical trial information: NCT02388919. ACC SCC Anlotinib n=228 Placebo n=108 HR P-value Anlotinib n=47 Placebo n=29 HR P-value Efficacy mPFS (mos) 5.53 1.37 0.21 <0.0001 5.63 2.70 0.39 0.001 mOS (mos) 9.63 6.93 0.67 0.0051 10.70 6.00 0.63 0.0932 ORR (%) 9.65 0.93 0.002 8.51 0 0.2933 DCR (%) 82.89 33.33 <0.0001 72.34 51.52 0.0866 Grade ≥3 AEs, n (%) Hyponatremia 13 (5.70%) 4 (3.70%) 9 (19.15%) 1 (3.45%) hand-foot syndrome 8 (3.51%) 0 (0%) 1 (2.13%) 0 (0%) Hypertension 28 (12.28%) 0 (0%) 9 (19.15%) 0 (0%) Hemoptysis 3(1.32%) 1 (0.93%) 5 (10.64%) 1 (3.45%)
Peritoneal metastatic desmoplastic small round cell tumor: A single institution experience.
Authors: Juliana Souza, Gelcio L. Q. Mendes
Journal: Journal of Clinical Oncology (2017)

e22541 Background: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive tumor that usually occurs in young males. The treatment remains a challenge and despite multiple strategies the tumor leads to death in most cases. Methods: Patients with peritoneal and metastatic DSRCT treated at or referred to National Cancer Institute of Brazil with histological documented diagnosis between July 1997 and September 2014 were identified and their medical records were analyzed. Results: There were 17 patients, the median age of diagnosis was 14.8 years (range: 4-49), with male-female ratio of 3.25. The most common sites of metastasis were liver (n: 7; 53.8%), lung (n: 6; 35%) and both (n: 2; 11.7%). Eight patients (47%) received radiotherapy and 15 patients (88.2%) received chemotherapy, 13 received vincristine, cyclophosphamide, doxorubicin and regimen with or without ifosfamide and etoposide. The median number of cycles received was 12.9 (range:1-27). Three patients (17.6%) who underwent to surgery, received the three treatments. Two patients received only palliative care. After median follow-up of 74 months, 13 patients (76.4%) died, nine patients during the first 2 years. The median overall survival was 16 months. One 6-year old patient was alive after 74 months, after chemotherapy, radiotherapy and surgery. Conclusions: The DSCRT is a rare disease with poor prognosis and high morbidity, that demand an aggressive approach. However, most patients are diagnosed with advanced disease, receiving noncurative approach.
Application of a cancer hot-spot panel to guide lung cancer therapy: Asian experience.
Authors: Yi-Ting Yang, Maarja-Liisa Nairismagi, Kai-Che Tung, Yen-Jung Lu, Ren-Shiang Jhou, Pei-Ning Yu, Yen-Ting Liu, Yi-Lin Hsieh, Song Ling Poon, Shu-Jen Chen, Kien Thiam Tan
Journal: Journal of Clinical Oncology (2018)

e21189 Background: Comprehensive genomic profiling (CGP) has transformed personalized medicine but is still not affordable to all patients, especially in developing countries. The price of CGP differs based on panel size. Here we explored the benefits of cancer hotspot panel over CGP in Asian lung cancer patients. Methods: 162 formalin-fixed, paraffin-embedded (FFPE) lung cancer clinical samples were subjected to next-generation sequencing using the Ion Torrent Proton System. 66 cases were profiled with a 35-gene cancer hotspot panel and 96 with pathway-based CGP (400+ genes) for base substitutions (single nucleotide variants and small indels) and copy number variants (CNV). Results: In total, actionable variants were discovered in 86.4% (57/66) cases using the cancer hotspot panel, with 57.9% (33/57) derived from base substitutions, 10.5% (6/57) from CNVs and 31.6% (18/57) from both alterations. Contrarily, CGP identified actionability in 97.9% (94/96) patients, 17.0% (16/94) of which were from base substitutions, 22.3% (21/94) from CNVs and 60.6% (57/94) from both. EGFR mutations were identified in comparable frequency with both panels, with almost half (48.8%; 79/162) of all samples harboring activating mutations in the tyrosine kinase (TK) domain. Identification of EGFR TK inhibitor (TKI) resistance mechanisms, including EGFR mutations (T790M and C797S), EGFR amplification, abnormal downstream EGFR signaling (KRAS, BRAF and PIK3CA mutations, PTEN loss) and activation of the bypass pathways (MET amplification, HER2 mutation and amplification), was equivalent with both panels. Additional targetable genetic alterations were detected in 70.0% (21/30) and 83.3% (39/47) of EGFR-wild type patients using the cancer hotspot assay and CGP, respectively. Conclusions: A cancer hotspot panel is sufficient to discover targetable genetic alterations and TKI resistance mechanisms in most Asian lung cancer patients.
ESKAPEade in hematological malignancies: Dare to review!
Authors: Cesar Giancarlo Gentille Sanchez, Kai Sun, Purnima Sravanti Teegavarapu, Mamta Puppala, Stephen Tc Wong, Qin Qian, Ibrahim Fuad Ibrahim, Lawrence Rice, Sai Ravi Pingali, Swaminathan Padmanabhan Iyer
Journal: Journal of Clinical Oncology (2017)

e18110 Background: Patients with hematological cancers are at a high risk for increasingly resistant and severe infections. The Infectious Diseases Society of America has defined commonly resistant bacteria as ESKAPE (Enterococcus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter, Pseudomonas aeruginosa, Enterobacter/Enterobacteriaceae). We performed a retrospective review of the rate of ESKAPE infections, resistance profile, and outcomes in patients with various hematological malignancies at the Houston Methodist Hospital from 2006 to 2015. Methods: The patient data was obtained from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse that contains records dating back to January 1, 2006 with over 3 million patients and over 10 million unique patient encounters. We queried for leukemia (AML, CML, ALL, CLL), amyloidosis and myelodysplastic syndrome (MDS) along with hospitalizations due to bacterial infections. Baseline demographics and overall outcomes were also obtained. Results: Out of 6017 patients with Hematological Malignancies, 632 patients were found; 322 had MDS, 225 had AML, 136 had CLL, 49 had ALL, 60 had CML, 97 had amyloidosis and 13 had an unspecified hematological cancer. Of 1091 infectious events, 60.5% were ESKAPE infections. The bacteria most frequently isolated were Enterococcus (24.7%), MRSA (19.8%) and Pseudomonas (18.0%). Patients with MDS (41.5%), AML (20.6%) and CLL (14.4%) were mostly affected. A prevalent resistance to levofloxacin was detected in gram positives and gram negatives (29-54%). Pseudomonas, E. coli, Proteus and K. pneumoniae showed a significant resistance to broad spectrum antibiotics including aztreonam (23-34%), cefepime (7-23%) and imipenem (22%). Proteus had the highest mortality rate (45.2%), followed by Enterococcus (44.2%) and Pseudomonas. (36.7%). Conclusions: Hematological cancers with risk for neutropenia such as MDS and AML were the most affected by ESKAPE. A significant resistance to levofloxacin, a prophylactic antibiotic, was seen. Gram negative pathogens had an increased resistance to broad spectrum antibiotics and higher mortality rates. New strategies for reducing ESKAPE in MDS and AML are required.
TCT-179 Trends and Outcomes in the Treatment of Cardiogenic Shock and Use of Mechanical Circulatory Support in The United States
Authors: Jad Omran, Tariq Enezate, Obai Abdullah, Ashraf Al-Dadah, Joseph Thomas, Daniel Walters, Belal Al-Khiami, Ryan Reeves, Mitul Patel, Ehtisham Mahmud
Journal: Journal of the American College of Cardiology (2018)