tbuckley/cabot-search huggingface dataset:
Clinical outcomes of 203 adult patients receiving highly (H) and moderately (M) emetogenic (E) chemotherapy (C) following an institutional antiemetic guideline update incorporating aprepitant (A) and palonosetron (P)
Authors: J. P. Timoney, W. W. Chan, A. E. Culkin, A. M. Flaherty, W. F. Giacalone, C. D. Lucarelli, D. J. Murphy, M. L. Schumann, M. A. Major, M. G. Kris
Journal: Journal of Clinical Oncology (2007)

19506 Background: A quality improvement project targeted at chemotherapy induced nausea (N) and vomiting (V) was initiated in 2004. The project included an antiemetic guideline update consisting of replacing ASCO 1998 3 tier guidelines with a 4 tier system similar to ASCO 2006. Following implementation of the guidelines an evaluation phase began. Methods: Adult chemotherapy-naïve patients receiving HEC or MEC were asked to participate. HEC patients received P 250 mcg IV each day of chemotherapy, A 125 mg PO day 1 and 80 mg PO days 2 and 3 and dexamethasone (D) 12 mg PO days 1, 2 and 3. MEC patients received P 250 mcg IV and D 12 mg PO on the day of C. Participating patients were asked to complete a 7 question NV tool at least 5 days following C to report on the 5 days following C. Outcomes reported include % of patients without N, % without V and N score using a 0–10 visual analog scale (VAS). Patient satisfaction with the the control of N and V was also assessed using a 0–10 VAS. Results: A total of 151 patients received HEC and 89% and 44% were protected from V and N respectively. A total of 52 patients received MEC and 90% and 56% were protected from V and N respectively The median N score for all patients who reported nausea was 3. The median and mean score for satisfaction with N and V control was 10 and 8.7 respectively. Patient outcomes for the most commonly used C regimens are reported in the table below. Conclusion: Implementation of revised AEG provided patients receiving HEC and MEC a high level of protection from vomiting, low nausea scores and a high level of overall satisfaction with prevention of N and V. Although N scores were low, the incidence of N reported offers an opportunity for further improvement. [Table: see text] No significant financial relationships to disclose.
Abstract MP32: Variation in NT-proBNP Levels After Bariatric Surgery and Its Association With Body Fat Percentage
Authors: Mariana Sbaraini Da Silva, Amelia Wallace, Elizabeth Selvin, Austin Burns, Justin B Echouffo Tcheugui, Gary Gerstenblith, Ron C Hoogeveen, Christie M Ballantyne, Josef Coresh, Chiadi E Ndumele
Journal: Circulation (2020)

Introduction: Natriuretic peptides are regulators of the cardiovascular system that are also related to adiposity and insulin resistance. NT-proBNP levels are inversely associated with adiposity and increase with weight loss, which may have hemodynamic implications in obesity. However, it is unclear if the changes in NT-proBNP with weight loss are independent of changes in insulin resistance and related metabolic risk factors. Hypothesis: NT-proBNP increases with surgical weight loss are partially independent of changes in other metabolic risk factors. Methods: We investigated 71 patients from the BARI-Heart Study, a prospective cohort with anthropometrics, metabolic risk factors and biomarkers before and after bariatric surgery. We compared data between pre- and post-surgical visits (1-2 weeks and 6 months, respectively) using t-tests, and performed regression analysis examining the association of changes adiposity measures with NT-proBNP before and after adjusting for metabolic risk factors. Results: After bariatric surgery, major reductions in weight, body-mass index (BMI) and body fat percentage (BFP) (mean change) were observed (Table 1), whereas NT-proBNP levels increased (mean change +61 pg/mL, SD 104). There were significant reductions post-surgery in HOMA-IR (from 9.9 to 2.6; p &lt;0.0001), as well as in triglycerides, total cholesterol, glucose, and blood pressure (all p&lt;0.05). A negative correlation between changes in ln-NT-proBNP and BFP was found ( r -0.27; p=0.03). In regression analysis, the inverse association remained statistically significant after adjustment for changes in the other metabolic risk factors (Table 2). Conclusions: Reductions in adiposity are linked to increases in NT-proBNP independent of changes in metabolic risk factors. The mechanisms and cardiovascular implications of this direct link between weight loss and NT-proBNP deserve further investigation.
Relationship between left ventricular ejection fraction and cardiovascular outcomes following hospitalization for heart failure: insights from the RELAX‐AHF‐2 trial
Authors: Satit Janwanishstaporn, Siting Feng, John Teerlink, Marco Metra, Gad Cotter, Beth A. Davison, G. Michael Felker, Gerasimos Filippatos, Peter Pang, Piotr Ponikowski, Thomas Severin, Claudio Gimpelewicz, Thomas Holbro, Chien Wei Chen, Iziah Sama, Adriaan A. Voors, Barry H. Greenberg
Journal: European Journal of Heart Failure (2020)
ET 743 is an effective agent against sarcoma
Authors: H. Boyle, B. Favier, A. Lurkin, I. Ray-Coquard, D. Ranchère, A. Decouvelaere, J. Blay, J. Fayette
Journal: Journal of Clinical Oncology (2007)

20516 Background: ET-743 has shown clinical activity in soft tissue sarcoma after failure of anthracyclines and ifosfamide. We propose to assess these results in our institution. Methods: We reviewed the patients treated (in phase II studies or on a compassionate basis) until June 2006 Results: Median age of the 99 patients was 53 years (18–82, with 20% leiomyosarcomas, 18% other spindle cell sarcomas, 12% liposarcomas, 9% osteosarcomas and 4% Ewing's sarcomas. The initial tumor was in the lower limbs in 31% of cases, and 70% had lung metastases. Patients had received anthracyclines (72%) or ifosfamide (61%), but 12% received ET-743 as their 1st chemotherapy. Most patients received ET-743 as a single agent, but 7 received it in combination with doxorubicin. After a median of 4 cycles (1–25), 50% of patients responded: 0 CR, 12 patients with PR, 4 MR (minor response), 34 SD and 49 progressed. Median time to progression for patients with a clinical benefit (PR+MR+SD) was 7 months (1.5 to 66 months). Among the 29 patients who didn't progress in the first six months, 10 had leiomyosarcomas and 8 spindle cell sarcomas. Grade3/4 toxicity, mainly hematological (42% neutropenia, 16% anemia, 11% thrombocytopenia) and hepatic (33%), was noted in 69 patients (28 needed a dose reduction). Main cause of treatment discontinuation was progression (70%) but 7 patients had to stop treatment because of toxicity. Conclusions: ET- 743 can benefit some patients with sarcomas, especially leiomyosarcomas, even pretreated. Some patients have long lasting responses. Grade ¾ toxicity is frequent but rarely leads to treatment discontinuation No significant financial relationships to disclose.
Audio Interview: What Clinicians Need to Know in Diagnosing and Treating Covid-19
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

What Clinicians Need to Know in Diagnosing and Treating Covid-19 In this audio interview conducted on March 3, 2020, the editors discuss the current state of SARS-CoV-2 diagnostic testing in the Un...
Feasibility of combining humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 (nimotuzumab) with chemotherapy-A study of toxicity profile and tolerance
Authors: D. Pendharkar, S. Gupta, M. K. Pal, S. Hakim, T. Rashid
Journal: Journal of Clinical Oncology (2007)

14151 Background. Anti-EGFR antibodies have been approved in combination with radiotherapy for the treatment of head and neck squamous cell carcinoma(SCCHN) and being tried in glioblastoma multiforme(GBM). The overall toxicity profile is tolerable. There is no data available on Humanized Anti EGFR antibody in combination with chemotherapeutic agents. Nimotuzumab, the humanized MAb derived from ior EGFR/R3, is a genetically engineered IgG1, with high affinity and specificity to EGFR. This study was undertaken to record the immediate and early toxicity of combining Nimotuzumab with various chemotherapeutic agents. Methods. Patients with SCCHN and GBM, scheduled to receive chemotherapy alone were additionally given 400mg of Nimotuzumab, every three weeks. Two patients with GBM received weekly Nimotuzumab 200 mg along with radiation and chemotherapy. Overall 19 events have been analyzed. The chemoschedules used in combination with Nimotuzumab included-Docetaxel, Carboplatin and Capecitabine in patients with SCCHN and Temozolamide/ Procarbazine in GBM. Antibody infusion was always preceded by antihistaminics and dexamethasone. Results.The combination of Nimotuzumab with chemotherapy was well tolerated. There were no acute infusion related events. No febrile, allergic or anaphylactic episodes were seen. Cutaneous rash classical of other EGFR blockers was not recorded. Two episodes of grade 3 diarrhea, and four events of asthenia were seen. Dryness of the mouth was a complaint in SCCHN patients. None of the patients showed neurological or cardiovascular adverse events. Hematological and biochemical derangements were not observed. Conclusion. Nimotuzumab can safely be combined with various chemotherapeutic agents .There is no unacceptable toxicity associated with combination of chemotherapy and humanized anti-EGFR monoclonal antibody. New schedules combining Nimotuzumab and chemotherapy can be safely explored. No significant financial relationships to disclose.
Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection
Authors: Louise Leyre, Eugène Kroon, Claire Vandergeeten, Carlo Sacdalan, Donn J. Colby, Supranee Buranapraditkun, Alexandra Schuetz, Nitiya Chomchey, Mark de Souza, Wendy Bakeman, Rémi Fromentin, Suteeraporn Pinyakorn, Siriwat Akapirat, Rapee Trichavaroj, Suthat Chottanapund, Sopark Manasnayakorn, Rungsun Rerknimitr, Phandee Wattanaboonyoungcharoen, Jerome H. Kim, Sodsai Tovanabutra, Timothy W. Schacker, Robert O’Connell, Victor G. Valcour, Praphan Phanuphak, Merlin L. Robb, Nelson Michael, Lydie Trautmann, Nittaya Phanuphak, Jintanat Ananworanich, Nicolas Chomont
Journal: Science Translational Medicine (2020)

Although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation.
Activated Src kinase is expressed in malignant pleural mesothelioma tumors; dasatinib inhibition leads to cytotoxicity, cell cycle inhibition, and prevention of invasion and migration
Authors: A. S. Tsao, D. D. He, B. Saigal, S. Liu, J. Lee, S. Bakkannagari, N. Ordonez, W. Hong, I. Wistuba, F. Johnson
Journal: Journal of Clinical Oncology (2007)

7713 Background: Malignant pleural mesothelioma (MPM) is a lethal disease with few effective therapeutic options. We sought to determine whether Src, a non-receptor tyrosine kinase, could be a new therapeutic target in MPM and to establish the potential therapeutic use of pharmacologic Src inhibitors in this disease. Methods: We analyzed four MPM cell lines (MSTO-211H, NCI-H28, NCI-H2052, and NCI- H2452) for immunohistochemical (IHC) expression of total and phosphorylated Src (Tyr 419, Tyr 530). These cell lines were treated with dasatinib, a Src inhibitor, and evaluated for apoptosis, cell cycle analysis, and migration and invasion. Downstream signaling events were studied by Western blot analysis. We also conducted IHC analyses with total Src, phosphorylated Src Tyr 419 (p-Src Tyr 419), and phosphorylated Src Tyr 530 on 46 archived MPM tumor specimens and correlated the biomarker results with the clinical outcome. Results: All four MPM cell lines expressed total and activated Src (p-Src Tyr 419). Three of the four cell lines were sensitive in vitro to cytotoxicity by dasatinib with inhibition of migration and invasion, cell cycle inhibition, and apoptosis. Treatment with dasatinib inhibited several pathways downstream of Src. In the archived MPM tumor specimens, Src protein was highly expressed on IHC analysis in tumor cells, but that expression did not correlate with overall or progression-free survival. However, expression of activated Src (p-Src Tyr 419) on the tumor cell membrane was higher in patients with stage 4 disease; the presence of metastasis correlated with higher membrane (P = 0.03) and cytoplasmic (P = 0.04) expression of p-Src Tyr 419. MPM nodal involvement at N1 was associated with the highest membrane expression of inactive Src (p-Src Tyr 530) (P = 0.02), whereas N2 disease was associated with the lowest expression. No gene mutations in Src exon 12 were found in the cell lines or tumor specimens. Conclusions: Activated Src may have an important role in survival, metastasis, and invasion in MPM, and targeting Src may be an important therapeutic strategy. No significant financial relationships to disclose.
Bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor: Preliminary results from a phase 1 study in patients with advanced malignant solid tumors
Authors: W. A. Messersmith, S. Krishnamurthi, B. A. Hewes, C. M. Zacharchuk, R. Abbas, P. Martins, E. Dowling, A. Volkert, E. Martin, A. I. Daud
Journal: Journal of Clinical Oncology (2007)

3552 Background: Bosutinib (SKI-606) is a potent, low molecular weight, orally active, competitive inhibitor of both Src and Abl tyrosine kinases. Elevations of Src kinase activity occur in a variety of human tumor types and are correlated with aggressiveness. We conducted a phase 1 study in patients (pts) with advanced solid tumors to assess tolerability, safety, pharmacokinetics (PK), and preliminary antitumor activity of bosutinib. Methods: Patients in cohorts of 3–6 received 50, 100, 200, 300, 400, 500 or 600 mg bosutinib orally on study day 1 and then once daily beginning on day 3. Timed blood samples were collected on days 1–3, 15 and 16 for PK analysis. Tumor assessments (modified RECIST criteria) were made at baseline and the end of every third cycle (21 days/cycle). Collection of tissue samples for analysis of Src biomarkers was optional. Results: Preliminary data are presented for 51 pts (median 57 years, 57% women). Three pts who received 600 mg bosutinib/day had drug-related dose-limiting toxicity of grade 3 diarrhea (2 pts) and grade 3 rash (1 pt). Gastrointestinal (GI) toxicity was reported among 6 pts in the 500-mg maximum tolerated dose (MTD) lead-in cohort so that 400 mg was selected as the MTD. Drug-related adverse events (AEs), any grade, occurring in =25% of pts were nausea (67%), diarrhea (55%), anorexia (45%), vomiting (43%), asthenia (41%). The only grade 3 drug-related AE occurring in =5% of pts was diarrhea (14%). After oral administration, bosutinib exposure increased in a dose-dependent manner. Multiple-dose exposure was nearly 2- to 3-fold higher than single-dose exposure. Mean elimination half-life was approximately 17 to 21 hours, supporting a once-daily dosing regimen. Six pts had stable disease &gt;15 weeks (2 pts each with breast, colorectal cancer, non-small cell lung cancer [NSCLC]) and 1 pt had stable disease &gt;52 weeks (pancreatic cancer). Conclusions: Bosutinib was generally well tolerated with predominantly gastrointestinal AEs. Accrual and evaluation of an expanded cohort restricted to patients with colorectal, pancreatic, and NSCLC tumors is ongoing. The patient with pancreatic cancer has had stable disease &gt;52 weeks. No significant financial relationships to disclose.
Abstract P166: Cardiovascular Disease Burden Among In-patients With Systemic Lupus Erythematosus
Authors: Laura P Kimble, Sandra B Dunbar, Elizabeth J Corwin, Rebecca Mitchell, Ignacio Sanz, Arezou Khosroshahi
Journal: Circulation (2020)

Introduction: Systemic lupus erythematosus (SLE) disproportionately affects minority women of childbearing age and is associated with increased cardiovascular risk. Understanding concomitant cardiovascular co-morbidities in the SLE population is essential to reduce their excess cardiovascular burden through targeted risk reduction. Purpose: This study examined cardiovascular co-morbidities in persons with SLE admitted to an acute care hospital. Method: We conducted a secondary data analysis of de-identified electronic health record (EHR) data from a random sample of 1,000,000 patients who received care from a healthcare system in the southeastern US between the years of 2012 and 2018. We targeted the specific patient encounter of the first hospitalization in which SLE was included as a discharge diagnosis and examined cardiovascular co-morbidities present in the cohort. Results: We identified 320 patients (89% women n=285/320, 84.4% n=270/320 African-American) with a mean age of 47.1 ± 16.4 years and length of stay (LOS) of 6.7 ± 8.1 days. The majority were hospitalized on an emergent basis (61%, n=195/320) with 44.4% (n=143/320) admitted to hospital medicine/internal medicine specialties. Admission to cardiology/cardiovascular surgery specialties was noted for 7.5% (n=27/320). The majority were discharged to home for self-care (70.9%, n=227/320) or home health services (12.5%, n=40/320). Potential SLE complications were evident with 23.7% (n=76/320) noted to have renal failure. The most common cardiovascular diagnoses documented in the EHR included: hypertension (40%, n=192/320), heart failure (18.4%, n=59/320), coronary artery disease (16.6%, n=50/320), mitral valve disorders (9.7%,n=31/320), atrial fibrillation (8.7%, n=27/320), supraventricular tachycardia (6.6%,n=21/320), acute myocardial infarction (6.2%,n=20/320), cerebral vascular accident (5.9%, n=19/320), endocarditis (4.1%,n=13/320), and peripheral vascular disease (3.7%, n=12/320). Longer LOS was associated with renal failure (r= .25, p = .001), heart failure (r= .20, p = .001), and supraventricular tachycardia (r=.22, p = .001). A greater proportion of men had endocarditis (14.3%, n=5/35), PVD (11.4%,n = 4/35), and CAD (28.6%, n=10/35) compared to women (endocarditis: 2.8%, n=8/285, p =.008; PVD 2.8%, n=8/285, p= .032; CAD 14.0% n=40/285, p=.044). Conclusion: Cardiovascular disease burden was evident in this predominantly young, female, African-American SLE inpatients. Cardiac diagnoses were associated with increased LOS and men with SLE had greater cardiovascular burden related to CAD and PVD compared to women. These findings highlight the importance of cardiovascular risk reduction interventions and aggressive management of cardiovascular comorbidities in the SLE population.
COVID-19: the medium is the message
Authors: Laurie Garrett
Journal: The Lancet (2020)

In a world of polarising distrust and trade tensions, the spread of coronavirus disease 2019 (COVID-19), both within nations and internationally, is aided and abetted by misinformation that circumnavigates the planet in microseconds. Such misinformation is not all malevolent, although its impact can be devastating. The only bastion of defence against rising public panic, financial market hysteria, and unintended misunderstandings of the science and epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is agile, accurate, worldwide-available counter-information that takes the high moral ground and conveys a consistently science-driven narrative.
Abstract P263: Understanding Facilitators Of Cardiac Rehabilitation Completion In Women: A Grounded Theory Approach
Authors: Lee Anne Siegmund, Christian Burchill, Sandra Siedlecki
Journal: Circulation (2020)

Research demonstrates that cardiac rehabilitation (CR) programs improve cardiac outcomes and decrease mortality. However, less than 20% of referred women attend CR programs. Of those studies we found, most researchers studied men or barriers to participation. Little is known about factors that motivate or facilitate women to participate in CR. The purpose of this study is to address that gap. A grounded theory (GT) design was used to develop a theoretical understanding of the decision-making process employed by women who attended 25 or more CR sessions. We sought to identify factors that facilitated CR participation. Grounded theory is theory generating, not theory testing; no research questions or hypotheses are appropriate. Digitally recorded interview data from 12 women and 2 men (contrary cases) from a single Phase II CR program at a large healthcare system was reviewed by the research team. Data collection and analysis occurred simultaneously (constant comparative method) and open, axial and selective coding was used to develop the theoretical framework. Data analysis revealed three requisite conditions (catalysts, expectations, reinforcers) for participation in CR by women. Initially, participation was predicated by a cardiac event (catalyst) and CR recommendation. Then women participated because they believed CR would be effective (expectations). Finally, friendliness, reassurance, and validation from the CR team plus feeling better (reinforcers) were the factors that kept them coming back week after week. Unlike previous studies, factors such as transportation and financial resources did not impact the decision to participate in CR. These factors were perceived by the women interviewed to be nice but not necessarily critical to their decision to participate in CR. It was interesting to note that of all reinforcing factors, the relationship between the participant and the CR staff was the most important factor that facilitated continued participation. Previous research and interventions have been directed toward removing barriers to participation. This is the first study to explore factors that facilitate rather than impede participation and to identify requisite factors specific to women. Findings from this study provide a theoretical foundation for understanding ways to improve CR participation by women.
Warning: not all carriers of pathogenic mutations in desmosomal genes should follow the same medical advices!
Authors: Silvia G Priori, Andrea Mazzanti
Journal: Cardiovascular Research (2020)

This work was supported by the Ricerca Corrente Funding Scheme of the Italian Ministry of Health (to S.G.P.). The Italian Ministry of Research and University Dipartimenti di Eccellenza 2018–2022 grant to the Molecular Medicine Department (University of Pavia).
Gemcitabine and docetaxel combination regimen in metastatic breast cancer (MBC)
Authors: D. Karacetin, O. Maral, O. Aksakal, B. Okten, B. Yalçın, O. Incekara
Journal: Journal of Clinical Oncology (2007)

1107 Background: No standart chemotherapy regimen has been estabilished for the treatment of patients with metastatic breast cancer. The gemcitabine and docetaxel combination has been shown to be synergistic . This study is conducted to verify the clinical efficacy and safety of gemcitabine and docetaxel combination therapy in metastatic breast cancer. Methods: 27 metastatic breast cancer patients were treated with gemcitabine-docetaxel combination . Gemcitabine 1,250 mg/m 2 IV infusion, on day 1 and 8, and docetaxel 70 mg/m 2 on day 1 in 21 day cycles. 4–6 cycles of chemotherapy were repeated every 3 weeks. The primary endpoint was response rate, and survival. Results: The median age was 50 years (range,32–77). Performans status (ECOG) was 0–1. Hormone receptor status: ER+/ER-; 11/16, PR+/PR-; 14/13. Menopausal status were: 11 premenopausal, 16 postmenopausal. Of the 27 evaluable patients, there were 11 (40.7%) partial responses and no complete response. Overall response rate was 40.7%. Median time to progression was 7 months, and median survival was 14 months. Toxicities included grade 3–4 neutropenia in 9 (30%), thrombocytopenia in 6 (22%), anemia in 3(9%). There were no treatment releated deaths Conclusions: The combination of gemcitabine and docetaxel has shown favorable toxicity profile and promising activity in metastatic breast cancer patients. No significant financial relationships to disclose.