tbuckley/cabot-search huggingface dataset:
Anesthesia Care Handovers and Risk of Adverse Outcomes
Authors: Vijay Krishnamoorthy, Karthik Raghunathan
Journal: JAMA (2018)

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Neo-/adjuvant phase III trial to compare intense dose-dense (idd) treatment with EnPC to tailored dose-dense (dt) therapy with dtEC-dtD for patients with high-risk early breast cancer: Results on pathological complete response (pCR) for patients treated within the neoadjuvant setting.
Authors: Volker Moebus, Stefanie Noeding, Ekkehart Ladda, Peter Klare, Marcus Schmidt, Andreas Schneeweiss, Wolfgang Janni, Frederik Marmé, Toralf Reimer, Sabine Schmatloch, Elmar Stickeler, Michael Untch, Bruno Valentin Sinn, Volkmar Müller, Peter A. Fasching, Gunter Von Minckwitz, Jenny Furlanetto, Nicole Burchardi, Sibylle Loibl
Journal: Journal of Clinical Oncology (2018)

568 Background: GAIN-2 compares the effectiveness and safety of a predefined idd regimen (EnPC) vs. a dd regimen with modification of single doses depending on individual hematological and non-hematological toxicities (dtEC-dtD) as neo-/adjuvant treatment for patients with high risk breast cancer (BC) (NCT01690702). Methods: Patients with high risk BC (HER2+; triple negative BC (TNBC); luminal B-like: ER and/or PgR+, HER2-, Ki67 > 20%, N+; luminal A-like: ≥4 N+) were randomized to receive either iddEnPC (epirubicin 150mg/m2 q2w, nab-Paclitaxel 330mg/m2 q2w, cyclophosphamide 2000mg/m2 q2w for 3 cycles each) or dtEC-dtD (epirubicin 60-100mg/m2 and cyclophosphamide 450-1200mg/m2 q2w for 4 cycles followed by docetaxel 60-100mg/m2 q2w for 4 cycles). The primary objective of the trial is to compare the invasive disease-free survival (iDFS) between the two arms. pCR rates in the breast per arm (ypT0) in the neoadjuvant cohort will be reported. Results: In total the GAIN-2 trial accrued 2887 patients. From 08/2016 to 07/2017 598 patients have been randomized in the neoadjuvant setting (EnPC n = 298; dtEC-dtD n = 300). Median age was 49 [range 20-69] years. Overall, 2.3% had bilateral tumors, 38.0% cT1, 52.7% cT2 and 9.3% cT3/4, 55.4% cN+; 62.9% G3; 88.0% had Ki67 > 20%; 17.6% had hormone-receptor (HR)-positive/HER2-, 1.7% luminal A ≥4 N+, 31.9% HR+/ HER2+, 13.7% HR-/HER2+ and 35.1% TNBC. In the modified intention-to-treat population (EnPC n = 291; dtEC-dtD n = 293) the pCR rates for iddEnPC vs dtEC-dtD were 53.6% vs 45.1% (corrected continuity Chi-Square p = 0.047). Overall, 34.8% of the patients had at least 1 severe adverse event (EnPC 38.3% vs dtEC-dtD 31.3%). Conclusion: The GAIN-2 trials shows a statistically significant difference in terms of pCR rates within the breast for patients with high-risk BC receiving iddEnPC compared to dtEC-dtD as neoadjuvant chemotherapy. Further analyses are ongoing. Clinical trial information: NCT01690702.
Piloting a screening tool in a breast cancer survivorship clinic.
Authors: Sheetal Mehta Kircher, Sofia F. Garcia, Megan Slocum, Joshua P Rutsohn, Allison Fisher, Christine B. Weldon, Frank J. Penedo
Journal: Journal of Clinical Oncology (2018)

66 Background: Breast cancer survivors experience physical, psychosocial, and practical concerns. Our Adult Survivorship Clinic provides patients a comprehensive survivorship visit following curative intent therapy to identify and address these needs. This study assessed patient and staff feasibility, usefulness, and burden of a screening tool. Methods: Patients seen in the Robert H. Lurie Breast Cancer Survivorship Clinic were randomly assigned to receive a screener (Coleman Supportive Oncology Tool including a concerns checklist &amp; the 4-item Patient Health Questionnaire [PHQ-4]) versus no screener prior to their survivorship clinic appointment. All patients were asked to complete the FACIT-TS-PS to assess treatment satisfaction following the appointment. The screener group also completed an additional set of screener acceptability questions. The survivorship clinician completed a questionnaire after each patient visit. Results: Patients with breast cancer (n = 100) were randomized. Twenty-six (52%) of the participants not given a screener and 26 (52%) of the participants given a screener completed the FACIT TS-PS. 48% of participants were age 55 years or older and 54% received chemotherapy. While there were no statistically significant differences between the groups, both groups scored high on the FACIT TS-PS. Screener patients provided high ratings for the satisfaction survey with 100% of the respondents reporting the screener was “probably” or “definitely” clear and relevant. 85% reported that the questions provided little or no distress. The median time to complete the tool was 4 to 5 minutes. The survivorship provider reported that in 47% of patients (23/49) the screener uncovered an additional significant concern. In 35% of screened patients (17/49), the provider felt the screener prompted an additional referral to supportive oncology services or a medical specialist. Conclusions: A comprehensive and brief screener for patient concerns was feasible and acceptable for both patients and provider. Even in the context of a comprehensive survivorship visit, a screening tool uncovered additional concerns that led to supportive care referrals.
Helicase-Driven Activation of NFκB-COX2 Pathway Mediates the Immunosuppressive Component of dsRNA-Driven Inflammation in the Human Tumor Microenvironment
Authors: Marie-Nicole Theodoraki, Saigopalakrishna Yerneni, Saumendra N. Sarkar, Brian Orr, Ravikumar Muthuswamy, Jamie Voyten, Francesmary Modugno, Weijian Jiang, Melissa Grimm, Per H. Basse, David L. Bartlett, Robert P. Edwards, Pawel Kalinski
Journal: Cancer Research (2018)

Abstract Presence of cytotoxic CD8+ T cells (CTL) in tumor microenvironments (TME) is critical for the effectiveness of immune therapies and patients' outcome, whereas regulatory T(reg) cells promote cancer progression. Immune adjuvants, including double-stranded (ds)RNAs, which signal via Toll-like receptor-3 (TLR3) and helicase (RIG-I/MDA5) pathways, all induce intratumoral production of CTL-attractants, but also Treg attractants and suppressive factors, raising the question of whether induction of these opposing groups of immune mediators can be separated. Here, we use human tumor explant cultures and cell culture models to show that the (ds) RNA Sendai Virus (SeV), poly-I:C, and rintatolimod (poly-I:C12U) all activate the TLR3 pathway involving TRAF3 and IRF3, and induce IFNα, ISG-60, and CXCL10 to promote CTL chemotaxis to ex vivo–treated tumors. However, in contrast with SeV and poly I:C, rintatolimod did not activate the MAVS/helicase pathway, thus avoiding NFκB– and TNFα-dependent induction of COX2, COX2/PGE2-dependent induction of IDO, IL10, CCL22, and CXCL12, and eliminating Treg attraction. Induction of CTL-attractants by either poly I:C or rintatolimod was further enhanced by exogenous IFNα (enhancer of TLR3 expression), whereas COX2 inhibition enhanced the response to poly-I:C only. Our data identify the helicase/NFκB/TNFα/COX2 axis as the key suppressive pathway of dsRNA signaling in human TME and suggest that selective targeting of TLR3 or elimination of NFκB/TNFα/COX2-driven suppression may allow for selective enhancement of type-1 immunity. Significance: This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. Cancer Res; 78(15); 4292–302. ©2018 AACR.
Absolute benefit from adjuvant chemotherapy in triple negative breast cancer (TNBC): A systemic review and meta-analysis.
Authors: Hadar Goldvaser, Domen Ribnikar, Habeeb Majeed, Alberto Ocana, Eitan Amir
Journal: Journal of Clinical Oncology (2018)

e12501 Background: In general, early stage TNBC has a poor prognosis. Adjuvant chemotherapy is the gold standard therapy and different regimens have shown improved outcome. It is uncertain whether all regimens have similar efficacy and if all patients with TNBC benefit equally from treatment. Methods: We searched PUBMED to identify randomized trials between 2007 and 2017 comparing different adjuvant chemotherapy regimens in breast cancer. Only studies reporting outcomes for patients with TNBC (or hormone receptor negative disease if data on TNBC not reported) were included. The absolute differences between the experimental and the control group for 5-year disease-free survival (DFS) and overall-survival (OS) were extracted. The absolute benefit from treatment was weighted by study sample size and pooled. We then compared differences between various generations of chemotherapy. Meta-regression analysis explored the influence of study-level median follow-up, tumor size, nodal status, median age, menopausal status and generation of chemotherapy on the benefit from adjuvant chemotherapy. Results: Nineteen studies comprising of 22 comparison groups and 11306 patients with TNBC were included in the analysis. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5 year DFS (weighted mean difference 7.4% for 3rd vs. 2nd generation and 5.9% for 2nd vs. 1st generation). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS (1.9%, 1.3% and -3.5% for studies comparing 3rd, 2nd and 1st generations, respectively). The weighted differences in 5 year OS were generally lower (0.4% to 5.8%). Meta-regression results are shown in the Table. Conclusions: Later generations of adjuvant chemotherapy result in substantially improved DFS in patients with early stage TNBC with patients with larger tumor size and nodal involvement gaining most benefit irrespective of age and menopausal status. Large differences in 5 year DFS do not translate to similar effects in 5 year OS. Variable DFS β P value Median age -0.144 0.63 Menopausal 0.374 0.21 T2-T4 0.822 0.001 Node positive 0.525 0.04 Follow-up duration -0.024 0.92
Abstract 16113: Similar Rates and Risk of Atrial and Ventricular Arrhythmias in Patients With Chemotherapy-induced Cardiomyopathy Compared to Other Forms of Non-ischemic Cardiomyopathy
Authors: Michael G Fradley, Federico Viganego, Kevin Kip, Angel Martin, Aarti Patel, Roohi Ismail-Khan, Sanders Chae, Bengt Herweg, Arthur Labovitz
Journal: Circulation (2016)

Introduction:  Chemotherapy induced cardiomyopathy (CIC) is a frequently identified cardiovascular complication of cancer therapy, especially with the use of anthracyclines. A proportion of these patients will require implantation of a defibrillator (ICD) for the prevention of sudden cardiac death. There is little information about arrhythmia burden in CIC patients.   Hypothesis:  We hypothesize that CIC patients will have similar rates and adjusted risk of atrial and ventricular arrhythmias compared to patients with other forms of non-ischemic cardiomyopathy (CMP).   Methods:  We performed a retrospective review of patients regularly followed in the University of South Florida device clinic, identifying 9 patients with CIC and an ICD and 18 age- and gender-matched control patients (9 non-ischemic and 9 ischemic CMP patients) for a total cohort of 27 patients. We excluded any patients who received an ICD for secondary prevention or those with high risk arrhythmic substrates. The odds of arrhythmias and ICD shocks were calculated by type of CMP, adjusted for days since ICD implant and atrial fibrillation history.   Results:  All CIC patients had breast cancer or leukemia/lymphoma, with the majority exposed to anthracyclines (86%). Mean time from chemotherapy to device implantation was 12.7 years (range 2-20 years). In our cohort, CIC and other non-ischemic CMP patients were more likely to receive a biventricular ICD than ischemic CMP patients (66.7%, 55.6%, 11.1%; p=0.0002). Compared to non-ischemic CMP patients, rates and adjusted odds were similar for CIC patients for atrial arrhythmias (44.4% vs. 33.3%; OR 1.79; CI 0.17-18.62; p=0.63), non-sustained ventricular tachycardia (NSVT) (44.4% vs. 33.3%; OR 2.13; CI 0.22-20.20; p=0.51), and the combined outcome of NSVT, sustained VT and/or VF (44.4% vs. 44.4%; OR 2.81; CI 0.26-30.09; p=0.11). In contrast, ischemic CMP patients demonstrated significantly higher rates and adjusted odds of the combined outcome (88.9% vs 44.4%; OR 23.74; CI 1.31-430.0; p=0.03).   Conclusion:  Rates of atrial and ventricular arrhythmias in patients with CIC appear to be similar to those experienced by patients with non-ischemic CMP. This is one of the first studies to quantitatively evaluate arrhythmia burden in this population.
Functional abdominal pain and discomfort (IBS) is not associated with faecal microbiota composition in the general population
Authors: Fabian Frost, Tim Kacprowski, Malte Christoph Rühlemann, Andre Franke, Femke-Anouska Heinsen, Uwe Völker, Henry Völzke, Ali A Aghdassi, Julia Mayerle, Frank U Weiss, Georg Homuth, Markus M Lerch
Journal: Gut (2018)

We read with interest the study by Simren et al 1 addressing the correlation between GI symptoms and functional GI disorders (eg, irritable bowel syndrome (IBS)) and the comment by Hadizadeh et al 2 reporting abdominal pain sensation to be associated with an altered faecal microbiota composition. Hadizadeh et al 2 propose from their study on 159 individuals that their results may allow to develop novel tools for diagnosis and management of IBS and dyspepsia. We tried to replicate their findings in the population-based Study of Health in Pomerania (SHIP-Trend)3 using stool samples from 906 volunteers to analyse faecal microbiota composition and diversity by 16S rRNA gene sequencing as previously described.4 Twenty participants were excluded for incomplete phenotypic data or antibiotic treatment at sample collection. Of the remaining 886 individuals (age: 51 years (40–61), median (first to third quartiles); female: 56.4%), 172 (19.4%) reported abdominal pain or discomfort for at least 3 days per month during the last 3 months (cases), whereas 714 did not (controls). To estimate …
Spirometric And Bodyplethysmographic Lung Function Is Associated With Echocardiography-Derived Ventricular Wall Stress In COPD
Authors: P. Alter, H. Watz, T. Welte, S. Glaser, H. Schulz, R. Bals, S. Sohler, A. Karch, C. Vogelmeier, R. A. Jorres
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Real-world (RW) characteristics, treatment (tx) patterns, and overall survival (OS) in US patients (pts) with metastatic breast cancer (mBC) and CNS metastases (CNS mets).
Authors: Ashwini Shewade, Angela Fu-Chi Hsieh, Aruna Mani, Nedal Jaffer Abdulla Al-Sakaff, Thibaut Sanglier, Michael Dennis Taylor, Dominik Heinzmann
Journal: Journal of Clinical Oncology (2018)

1037 Background: About 10–16% of mBC pts are reported to have a CNS mets diagnosis (dx; Lin JCO 2004). Data on the management of these pts are limited because they are often excluded from clinical trials due to significant morbidity and mortality. We aim to describe RW characteristics, tx patterns, and OS of mBC pts with CNS mets using an oncology electronic health record database (EHR Db). Methods: Flatiron Health’s Db is longitudinal, demographically and geographically diverse, and derived from EHR data. Female pts with ≥2 clinic visits within the Flatiron network following mBC dx made between Jan '11–Jul '17 were included and followed until Oct '17. CNS mets dx was ascertained based on dx codes and/or unstructured part of EHR. mBC subtype was defined using HER2 and hormone receptor (HR) status. Demographic, clinical, systemic tx, and mortality data were used to characterize mBC pts with CNS mets. Results: As of 10/31/'17, the analysis cohort included 10145 mBC pts; 1837 had CNS mets dx during the study period. The table describes incidence of CNS mets by subtype, characteristics at mBC dx for pts with CNS mets, and median OS after CNS mets. Depending on whether CNS mets dx was made at or after mBC dx, among pts with CNS mets and a tx recorded after CNS mets, pts with HER2+ dx commonly (70%/65%, respectively) received tx regimens containing HER2-targeting monoclonal antibodies (MAb), HER2–/HR+ dx commonly (51%/74%) received regimens containing hormonal/other targeted tx or chemotherapy, and triple-negative (TNBC) dx commonly (90%/82%) received chemotherapy. Conclusions: CNS mets continues to be an unmet medical need. HER2+/HR– and TNBC have the highest prevalence and/or incidence of CNS mets, whereas HER2–/HR+ has the lowest. HER2+ mBC pts with CNS mets commonly receive subsequent tx including HER2-targeting MAbs and show a trend towards better survival from CNS mets dx than HER2–/HR+ and TNBC. All mBC (n = 10145) HER2+/HR+ (15%) HER2+/HR– (6%) HER2–/HR+ (66%) TNBC (13%) % CNS mets 18 24 32 13 31 Prevalence at mBC dx, % 8 10 15 5 15 Incidence rate/100 person yrs 7 8 12 5 19 For CNS mets pts Median age, yrs 58 56 55 60 57 % de novo mBC 29 32 40 25 28 Median OS after CNS mets dx, mo 11 20 19 10 7
Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia
Authors: Samir H. Barghout, Parasvi S. Patel, Xiaoming Wang, G. Wei Xu, Simon Kavanagh, Ondrej Halgas, Sara F. Zarabi, Marcela Gronda, Rose Hurren, Danny V. Jeyaraju, Neil MacLean, Shawn Brennan, Marc L. Hyer, Allison Berger, Tary Traore, Michael Milhollen, Adam C. Smith, Mark D. Minden, Emil F. Pai, Razq Hakem, Aaron D. Schimmer
Journal: Leukemia (2018)
Balancing the risks versus benefits of trastuzumab: A call to action for oncologists, cardiologists, and cardio-oncologists.
Authors: Moira Katherine Rushton, Isac Lima, Christopher Johnson, Meltem Tuna, Steven Hawken, Susan Faye Dent
Journal: Journal of Clinical Oncology (2018)

554 Background: One year of adjuvant trastuzumab (T) is standard for early stage (I-III) HER2 + breast cancer (BC) patients (pts). Cardiac imaging is recommended every 3 months during treatment to monitor for cardiotoxicity (CTx) without evidence this practice improves pt care. Up to 30% of pts will experience transient, asymptomatic, drops in left ventricular ejection fraction (LVEF) on T, which may lead to early termination of T. Our objective was to evaluate the impact of routine CI on disease free (DFS) and overall survival (OS) in early stage HER2+ BC. Methods: Retrospective population-based cohort study of early stage BC pts treated with adjuvant T in Ontario, Canada, 2007–2016. Patient-level data was sourced through the Institute for Clinical Evaluative Sciences, which captures all patients in Ontario. The cohort was divided into three arms; A: 17-18 cycles T, no CTx; B: no CTx, ≤16 cycles T, stopped within 30 days of last cardiac imaging; C: developed CTx. CTx was defined as new diagnosis heart failure (HF), cardiomyopathy (CM) or pulmonary edema within 90 days of last cycle of T. Primary outcome: DFS; secondary outcomes: OS, cancer-specific, and cardiovascular mortality. Survival analysis was performed using Cox and subdistribution hazard models. Results: 4820 pts met inclusion criteria; 4018, 442 and 360 in arms A, B, and C respectively. Median cycles of T were 18, 13 and 14 in arm A, B and C. 5-year DFS was significantly worse in arms B (70.3%; 95% CI 63.5-74.7) and C (74.9%; 69.5-79.5) vs. 93.2% (92.3-94.0) arm A; HR for DFS were 2.96 (2.35-3.72) and 2.41 (1.87–3.12) respectively. 5-year OS was significantly worse in arms B (75.4%) and C (80.1%) vs. arm A (95.2%); HR for OS 3.99 (3.10–5.14) and 2.98 (2.24–3.95) respectively. All p-values were < 0.05. Conclusions: BC pts in Ontario who did not complete adjuvant T had significantly worse DFS and OS. A significant population stopped T shortly after cardiac imaging, without developing CTx, likely due to detection of asymptomatic drops in LVEF. These findings support the need to consider strategies to continue cancer therapy in pts with abnormal cardiac imaging, including concurrent optimization of cardiac function and cardiac risk factors.
Abstract 2605: Hypoglycemia Does Not Increase Long-term Mortality Or Morbidity In Diabetic Patients With Myocardial Infarction. A Report From The Digami 2 Trial.
Authors: Linda G Mellbin, Klas Malmberg, Anders Waldenstrom, Hans Wedel, Lars Ryden
Journal: Circulation (2007)

Aims Tight, insulin-based glucose control is recommended to diabetic patients (DM pat) with acute myocardial infarction (AMI). A potential draw-back would be if insulin induced hypoglycaemia (HG) had a negative impact of future prognosis. Methods 1253 pat (mean age 68 years; 67% males) with type 2 DM and suspect AMI were followed for a median of 2.1 years. 947 were randomised to insulin infusion during at least 24 hours while 306 were treated routinely. HG (blood glucose&lt;3.0 mmol/L with or without symptoms) was recorded during hospitalisation. Unadjusted and adjusted (age, sex, smoking, previous MI and heart failure, renal function, duration of DM, coronary interventions, blood glucose at randomisation) Hazard Ratios (HR) and 95% Confidence Intervals (CI) for cardiovascular events (CVE = death, MI or stroke) during follow up were calculated. Results 153 pat (12.2%) experienced HG. During the first 24 hours 111 (11.7%) insulin-treated pat experienced HG (symptomatic 23.4%) compared with 3 (1.0%) pat on routine treatment (symptomatic 33.3%). As outlined in the figure HG was not an independent predictor of subsequent CVE. Conclusion Insulin induced HG was not a significant risk factor for subsequent CVE in AMI-pat with type 2 DM. Hypoglycaemic seem to identify patients at high risk for other reasons.
Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure
Authors: Anna Frey, Roxane Sell, György A. Homola, Carolin Malsch, Peter Kraft, Ignaz Gunreben, Caroline Morbach, Bálint Alkonyi, Eric Schmid, Isabella Colonna, Edith Hofer, Wolfgang Müllges, Georg Ertl, Peter Heuschmann, László Solymosi, Reinhold Schmidt, Stefan Störk, Guido Stoll
Journal: JACC Heart Failure (2018)