tbuckley/cabot-search huggingface dataset:
Abstract 2055: Non-Invasive Measurements for Predicting Duration of Untreated Cardiac Arrest
Authors: Giuseppe Ristagno, Jun H Cho, Tao Yu, Yongqin Li, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2008)

Objective. Initial chest compression rather than defibrillation has evolved as the initial intervention when the duration of untreated cardiac arrest exceeds 4 min. Accordingly, we sought methods by which the duration of untreated cardiac arrest could be reliably estimated and communicated to the rescuer. Both AMSA (the amplitude spectrum area) together with measurements of tissue PCO 2 in the buccal mucosa (P BU CO2) were investigated. We hypothesized that decreases in AMSA, reflecting reduced myocardial electrical function, and increases in P BU CO 2 , reflecting the severity of anaerobic metabolism, would fulfil this need. Materials and Methods. In 9 domestic male pigs weighing 41 ± 2 kg, ventricular fibrillation (VF) was electrically induced and untreated for 15 min. AMSA was analyzed by fast Fourier transform from the ECG signal obtained through conventional precordial electrodes. P BU CO 2 was continuously measured utilizing a miniature optical sensor system (CO 2 ABG Module, Vasomed, Minneapolis, MN) applied non-invasively on to the buccal mucosa. Results . After 3 min of untreated VF, the AMSA value decreased significantly (p &lt; 0.01, Figure ). P BU CO 2 progressively increased, exceeding threshold levels after 4 min. AMSA and P BU CO 2 were remarkably highly correlated with the durations of untreated cardiac arrest (r = 0.99 and r = 0.92, p &lt; 0.0001) and with each other (r = −0.95, p &lt; 0.0001). Conclusion. AMSA and P BU CO 2 both represent methods by which the duration of untreated cardiac arrest may be identified such as to prompt rescuer to immediately defibrillate or begin chest compression.
PD-1 Blockade after Epigenetic Therapy in Patients with Relapsed or Refractory Hodgkin Lymphoma: Higher-Than-Expected Rate of Complete Responses
Authors: Lorenzo Falchi, Ahmed Sawas, Changchun Deng, Jennifer E Amengual, Emily Lichtenstein, Karen Khan, Lawrence H. Schwartz, Owen A. O'Connor
Journal: Blood (2016)
Effect of Short Procedural Duration With Bivalirudin on Increased Risk of Acute Stent Thrombosis in Patients With STEMI
Authors: Hector Tamez, Duane S. Pinto, Ajay J. Kirtane, Claire Litherland, Robert W. Yeh, George D. Dangas, Roxana Mehran, Efthymios N. Deliargyris, Guillermo Ortiz, C. Michael Gibson, Gregg W. Stone
Journal: JAMA Cardiology (2017)

Bivalirudin has been associated with reduced bleeding and mortality during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). However, increased rates of acute stent thrombosis (AST) have been noted when bivalirudin is discontinued at the end of the procedure, which is perhaps related to this medication's short half-life.To evaluate the clinical effect of procedure duration on AST when either bivalirudin or heparin plus glycoprotein IIb/IIIa receptor inhibitor (GPI) is used.An ad hoc analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) clinical trial was performed between March 1, 2015, and April 30, 2016, on patients who underwent primary percutaneous coronary intervention with stents and were randomized 1:1 to bivalirudin or heparin plus GPI. Defined as the difference between the patient's arrival at the catheterization laboratory and the patient's final angiogram. Participants included 3602 patients with STEMI, aged 18 years or older, who were undergoing primary percutaneous coronary intervention and presenting less than 12 hours from symptom onset.Clinical events committee-adjudicated definite AST (occurring ≤24 hours after percutaneous coronary intervention).Among patients included in this analysis, procedure time was identified in 1286 receiving bivalirudin and 1412 receiving heparin plus GPI. Shorter procedures were defined as the lowest quartile of duration (<45 minutes). Patients undergoing shorter procedures were younger and less likely to be hypertensive and smokers. Shorter procedures were less complicated with fewer stents implanted, less multivessel stenting, less thrombus, and less no-reflow. An increased risk of definite AST was associated with shorter than with longer procedures with bivalirudin (7 [2.1%] vs 7 [0.7%]; relative risk, 2.87; 95% CI, 1.01-8.17; P = .04) but not with heparin plus GPI (0 vs 3 [0.3%]; P = .30).Despite less procedural complexity, shorter primary percutaneous coronary intervention time was associated with an increased risk of AST in patients treated with bivalirudin but not patients treated with heparin plus GPI, possibly because of the rapid offset of bivalirudin's antithrombotic effect during a window of limited oral antiplatelet action.clinicaltrials.gov Identifier: NCT00433966.
The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic
Authors: S. Mashayekhi, C. Flohr, F.M. Lewis
Journal: British Journal of Dermatology (2017)

Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.
Identification of Prognostic Markers by Gene Expression Profiling In Myelodysplastic Syndrome Hematopoietic Stem Cells
Authors: Andrea Pellagatti, Mario Cazzola, Aristoteles Giagounidis, Janet Perry, Luca Malcovati, Matteo G. Della Porta, Martin Jädersten, Sally Killick, Paresh Vyas, Eva Hellström-Lindberg, Jacqueline Boultwood, James S. Wainscoat
Journal: Blood (2010)
Finding an appropriate dose of fentanyl effervescent buccal tablets for relief of cancer-related breakthrough pain
Authors: J. K. Weick, L. Tremmel, J. Messina, R. K. Portenoy
Journal: Journal of Clinical Oncology (2006)

8564 Background: The recommended dose of a short-acting oral opioid used to treat cancer-related breakthrough pain (BTP) is 5%-15% of the equianalgesic around-the-clock (ATC) opioid dose used to control persistent pain; however, this dosing strategy may not be successful when oral transmucosal fentanyl citrate is used. The applicability of this strategy to fentanyl effervescent buccal tablets (FEBT) use was assessed as part of a multicenter study in opioid-treated patients with cancer BTP. Methods: This double-blind, randomized, placebo-controlled, crossover study required 63 evaluable patients for adequate statistical power. Eligible adults were to receive ≥60 mg/day morphine or equivalent for chronic cancer pain and to have experienced 1–4 BTP episodes daily. After open-label titration to an effective FEBT dose, patients were randomized to 1 of 18 predefined sequences of 10 tablets (7 FEBT, 3 placebo). Pain was assessed repeatedly after each dose; the primary efficacy variable was the sum of pain intensity differences at 30 minutes postdose (SPID 30 ). Results: Of 123 enrolled patients, 77 found an effective FEBT dose (100–800 μg) and continued in the double-blind period; 72 were evaluable for efficacy. The SPID 30 was 3.0±0.12 (mean±SE) for FEBT vs 1.8±0.18 for placebo (P&lt;.0001). Ratios of the effective FEBT dose to ATC opioid or prior supplemental opioid dose showed no consistent trend (table). An effective FEBT dose showed no meaningful correlation with prior supplemental dose (r 2 =.094; Pearson’s coefficient=.3066), with ATC dose in patients using oral opioids (r 2 =.0609; Pearson’s coefficient=.2468), or with ATC dose in patients using transdermal fentanyl or combinations (r 2 =.1842; Pearson’s coefficient=.4292). Conclusions: There was no relationship between the effective FEBT dose and either ATC opioids or prior supplemental drugs. Therefore, titration, rather than use of a percentage of the ATC dose, is likely to be important in establishing an effective FEBT dose for each patient. [Table: see text] [Table: see text]
A phase II study of afatinib (BIBW 2992) in patients with advanced HER2-positive trastuzumab-refractory esophagogastric cancer.
Authors: Yelena Yuriy Janjigian, David Ilson, David Paul Kelsen, Mark Schattner, Adriana Heguy, Efsevia Vakiani
Journal: Journal of Clinical Oncology (2012)

TPS4144 Background: Trastuzumab, approved by the FDA, has been the standard of care for patients (pts) with HER2-positive esophagogastric cancer. Acquired and de novo resistance to trastuzumab is an important clinical issue. Afatinib, an oral irreversible inhibitor of the ErbB-family of tyrosine kinase receptors, EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4), in combination with cetuximab, demonstrated a 40% partial response (PR) rate, with clinical benefit in &gt;90% in lung cancer patients with acquired resistance to erlotinib. (Janjigian Y. ASCO 2011). MSKCC data in a HER2-positive NCI-N87 gastric cancer xenograft showed that while trastuzumab alone was minimally effective, single-agent afatinib resulted in near complete tumor regression by inducing apoptosis and downregulation of HER2, p-HER2, EGFR, p-EGFR with minimal additive benefit of trastuzumab. In light of these data and the efficacy of afatinib in patients with trastuzumab-refractory breast cancer, we designed a phase II study to determine if afatinib will benefit patients with trastuzumab-refractory HER2-positive esophagogastric cancer. We hypothesize that simultaneous inhibition of ErbBB receptor family components with afatinib will overcome trastuzumab resistance. Molecular bases of trastuzumab resistance will be examined. Methods: Pts with metastatic HER2-positive (IHC 3+ or FISH &gt;2.0) esophagogastric cancer with disease progression on a trastuzumab-containing regimen will receive afatinib 40 mg once daily. Primary endpoint RECIST 1.1 response (SD+CR+PR) at 4 months, with imaging every 8 wks. 13 pts will be enrolled in the 1st stage and if ≥1 responses are observed, additional 14 ps (total of 27) will be treated. An initial biopsy prior to the start of therapy, a second biopsy after 1 wk of afatinib, analysis of archival pre-trastuzumab tissue and blood sample for matched normal DNA control are mandated. Changes in signaling following afatinib therapy will provide insight into response heterogeneity. Degree of target inhibition will be correlated with responses. Archival baseline (pre-trastuzumab) and pre-afatinib tissue will be assessed for abnormalities in pathways implicated in trastuzumab resistance.
Recombinant Granulocyte-Macrophage Colony-Stimulating Factor after Autologous Bone Marrow Transplantation for Lymphoid Cancer
Authors: John Nemunaitis, Susan N. Rabinowe, Jack W. Singer, Philip J. Bierman, Julie M. Vose, Arnold S. Freedman, Nicole Onetto, Steven Gillis, Dagmar Oette, Morris Gold, C. Dean Buckner, John A. Hansen, Jerome Ritz, Frederick R. Appelbaum, James O. Armitage, Lee M. Nadler
Journal: New England Journal of Medicine (1991)

The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocytemacrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation.
The Incidence and Outcome of Acute Lymphoblastic Leukemia in Shanghai, China Over 5 Years (2002–2006)
Authors: Xiong Ni, Zhixiang Shen, Fangyuan Chen, Hui Liang, Fengjuan Lu, Jingyan Tang, Chun Wang, Jingbo Shao, Jian Hou, Shanhua Zou, Jianmin Wang
Journal: Blood (2008)
Abstract OT2-01-18: RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole
Authors: PA Fasching, T Decker, T Fehm, W Janni, S Kuemmel, D Lueftner, A Schneeweiss, M Schuler, G Guderian, S Schmidt-Wetzel, R Reiners, J Schubert, S Brucker
Journal: Cancer Research (2017)

Abstract Introduction: The double blind, placebo-controlled MONALEESA-2 trial met its primary endpoint of clinically meaningful improvement in PFS at the pre-planned interim analysis for the combinatorial treatment of the cyclin-dependent kinase (CDK) 4/6-Inhibitor ribociclib and letrozole vs. letrozole monotherapy for postmenopausal, estrogen receptor positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) women who were naïve to treatment for advanced disease. Here we present the national, multi-center, open-label, single-arm phase IIIb trial RIBECCA assessing the efficacy and safety of the combination of ribociclib and letrozole in an additional population, accompanied by a set of exploratory objectives. Methods: Main inclusion criteria allow enrollment of women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, and histological or cytological confirmation of ER+, HER2- breast cancer, irrespective of their menopausal status. The primary objective is to assess the Clinical Benefit Rate (CBR) after 6 months, the secondary objectives include progression free survival (PFS), overall survival (OS), safety and change in quality of life. The exploratory objectives include the assessment of biomarkers (e.g. ctDNA, CTCs, miRNA) predictive for response and the occurrence of adverse events of special interest. The influence of CDK4/6-inhibition on the immune system will be another exploratory endpoint of this study. Conclusion: With a planned recruitment of 500 patients in about 100 trial sites the RIBECCA trial will contribute to a better understanding of the safety, efficacy and possibly mechanisms related to CDK4/6-inhibition through ribociclib. Citation Format: Fasching PA, Decker T, Fehm T, Janni W, Kuemmel S, Lueftner D, Schneeweiss A, Schuler M, Guderian G, Schmidt-Wetzel S, Reiners R, Schubert J, Brucker S. RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-18.
Assessing the Phenotypic Burden of Preclinical Sarcomeric Hypertrophic Cardiomyopathy—New Assessments to Guide Diagnosis and Management
Authors: Jil C. Tardiff
Journal: JAMA Cardiology (2017)

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Identification of Single Nucleotide Polymorphism Interactions Associated with Survival and Risk In Multiple Myeloma Using Novel Data Mining Methods
Authors: Brian Van Ness, Majda Haznadar, Gang Fang, Wen Wang, Vanja Paunic, Michael Steinbach, Vipin Kumar, Patrick Day, Johnson David, Gareth J Morgan, Bart Barlogie, Brian GM Durie
Journal: Blood (2010)
Abstract P1-05-21: A comparison of oncotype DX recurrence scores in a screen detected vs a symptomatic cohort of patients with breast cancer: A UK experience
Authors: S Khawaja, A Parab, D Thomas, A Huws, A Munir, S Udayasankar, Y Sharaiha, S Holt
Journal: Cancer Research (2017)

Abstract Background: In the Western World, it has been stated that breast cancers detected on a screening program are indolent. There have been many recent publications stating that breast screening is overdiagnosing and therefore overtreating patients with breast cancer. With the advent of genomic testing, it can now be determined which patients have an aggressive tumor requiring systemic chemotherapy. We therefore conducted a retrospective study in the UK on patients having oncotype DX testing in both screen detected and symptomatic cancers. Materials and Methods: Patients in our institution undergoing oncotype DX testing for invasive breast cancer which was ER positive and node negative were part of this study. The detection of the breast cancer was documented as either a screening case or a symptomatic one. The recurrence scores of the oncotype DX testing was then compared in the screening versus the symptomatic cohort. Results: 155 patients were included in this study. They underwent Oncotype DX testing between 2008 to 2016. The age of the patients ranged from between 31 years to 78 years. Eighty-nine patients were reported to have a low recurrence score; 45 had an intermediate score; and 21 had a high result. Fifty eight patients were screen detected, while 97 patients were symptomatic presentations. In the screening population, 32 patients had a low recurrence score; 22 had an intermediate result and 4 had a high recurrence score resulting in the latter groups being considered for chemotherapy. In the symptomatic cohort, 57 had a low recurrence score; 23 had an intermediate result; and 17 had a high score. Conclusion: The results of our study depict that even patients in a screeining cohort will have a high number of intermediate recurrence scores and some with a high recurrence score. This shows that the hypothesis that screening detects a majority of breast cancers which are indolent not requiring further systemic treatment should be looked at again in light of our results with genomic testing. Citation Format: Khawaja S, Parab A, Thomas D, Huws A, Munir A, Udayasankar S, Sharaiha Y, Holt S. A comparison of oncotype DX recurrence scores in a screen detected vs a symptomatic cohort of patients with breast cancer: A UK experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-21.
Characterisation of Molecular Relapse Profiles after Tyrosine Kinase Inhibitor Cessation in Patients Eligible for Treatment-Free Remission Strategies in Chronic Phase CML
Authors: Franck E Nicolini, Vincent Alcazer, Stephanie Dulucq, Marie Balsat, Helene Labussiere, Helene Lequeu, Mohamad Sobh, Stephane Morisset, Pierre Sujobert, Francois-Xavier Mahon, Gabriel Etienne
Journal: Blood (2016)
Use of RIC-Allosct In Patients Younger Than 45 Years Old Affected by MDS and Leukemia: A Monocenter Retrospective Analysis.
Authors: Roberto Crocchiolo, Luca Castagna, Sabine Furst, Jean El Cheikh, Catherine Faucher, Raynier Devilliers, Alberto Vazquez, Nawel Belmecheri, Angela Granata, Evelyne D'Incan, Norbert Vey, Didier Blaise
Journal: Blood (2010)
Abstract P1-05-18: Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T)
Authors: N Walsh, G Gullo, A Maguire, N O'Donovan, C Quinn, J Crown
Journal: Cancer Research (2017)

Abstract Introduction: Genetic alterations such as amplifications and deletions frequently contribute to tumorigenesis. These alterations can change gene expression which alters the normal cell growth and survival regulatory mechanisms. Characterisation of DNA copy number alterations (CNA) is important to understand cancer progression and response to therapy. The aim of this study is to determine patterns of CNAs in HER2+ early-stage BrCa patients achieving pathological complete response (pCR) to neoadjuvant T therapy. Methods: Retrospective analysis of our database of 95 HER2+ BrCa (stages I-III) who received T neoadjuvantly revealed 46 % (44/95) achieved pCR compared with 53 % (51/95) who did not respond (NR). DNA from pre-treatment tumour biopsy specimens from neoadjuvant T therapy patients was extracted, and array-based comparative genomic hybridization (aCGH, n = 8; 6 pCR:2 NR) was used to identify CNAs, which correlated with pCR. Pathway analysis was then used to identify functionally relevant genes in aberrant regions. Results: aCGH analysis of DNA from pCR and NR identified distinct patterns of CNAs. HER2 amplicon was confirmed by IHC and aCGH in all samples. Although there was no significant difference in the average CNAs between groups (20±17 vs 17±2), there was greater variation in the range of CNAs in pCR (8-56 CNA) compared to NR (15-19 CNA). More gains and amplifications were observed in pCR patients with more deletions in the NR group. The most common chromosomal amplification region included chr8q12.1-q24 with 87.5% of all cases displaying gains. Of the 6 patients who achieved pCR, 50% displayed a deletion in chr9 spanning p24.3-p21.3, consistent with a deletion of tumour suppressor CDKN2A. No aberrations in chr9 were observed in NR cohort. The deleted genomic region contained 65 common protein-coding genes, with the interferon biological pathway as the most significant (p=1.03E-36). Conclusions: Distinct genomic CNAs were observed between patients achieving pCR compared to NR. However, of the 8 pts characterised here, none have relapsed. Follow-up data revealed a relapse rate of 6.8 % (3/44) vs 11.8 % (6/51) in the pCR and NR groups, respectively. To further elucidate the immunological response, we will present CNA data patterns on relapse and response and compare the impact of CNAs, immune-related proteins and pCR as surrogate predictors for outcome. Citation Format: Walsh N, Gullo G, Maguire A, O'Donovan N, Quinn C, Crown J. Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-18.