tbuckley/cabot-search huggingface dataset:
ERBB3 mutations in advanced gastric signet-ring cell carcinoma (SRCC) and the implications for targeted therapy
Authors: J. Wei, B. XU, S. Jin, L. Yu, B. Liu
Journal: Annals of Oncology (2017)

Background: Studies have shown that ERBB3 mutations are associated with poor clinical prognosis by increasing the rate of metastasis and recurrence in many cancers. ERBB3 targeted therapeutics can be effective against ERBB3 mutant-driven tumors. ERBB signal pathway plays a very important role in the initiation and progression of gastric cancer, however the ERBB2 expression and mutation rate is relative low especially in gastric SRCC. Thus, ERBB3 might be a promising target for the treatment in SRCC patients. The aim of this study is to speculate the prognostic and targeted therapy value in gastric SRCC by evaluating the mutation rate and type of ERBB3. Methods: 92 patients with histological diagnosis of advanced gastric SRCC were retrospectively selected for this study. ERBB3 mutation was evaluated by next generation sequencing from formalin-fixed paraffin-embedded (FFPE) samples. ERBB2 expression was tested by immunohistochemistry. Correlations between ERBB2/3 status and clinical pathologic characteristics and overall survival (OS) were performed. Results: All of the 92 patients were diagnosed as local advanced or metastatic gastric SRCC (92.4% were stage III, 7.6% were stage IV). All the patients received 5-FU-based first-line chemotherapy. 14 out of all 92 patients were ERBB3 mutated SRCC, 12 of all the 14 mutations were in the extracellular domain, 2 were in the transmembrane region. There was no correlation between ERBB3 mutation and serosa invasion (P = 0.389) or lymph node metastasis (P = 1.000). The median OS was 20.5 months (95% CI = 10.05to 30.95 months) for patients with ERBB3 mutation, and 19.0 months (95% CI = 15.54 to 22.46 months) for patients without ERBB3 mutation (P = 0.567). There was no difference in OS according to HER2 positive or negative in ERBB3 mutated patients (14.8 months vs 20.5 month, P = 0.374). Conclusions: Our study demonstrated 15.2% of gastric SRCC patients harboring ERBB3 mutation, providing a potential subgroup of gastric SRCC for targeted treatment on ERBB pathway. No difference of OS was observed, probably due to the relative small sample size and low ERBB2 positive rate in SRCC patients. Further investigation on ERBB3 is warranted to clarify mechanisms of ERBB pathway in gastric SRCC. Legal entity responsible for the study: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China Funding: None Disclosure: All authors have declared no conflicts of interest.
Phase II California cancer consortium trial of gemcitabine-eribulin combination (ge) in cisplatin ineligible patients (pts) with metastatic urothelial carcinoma (mUC): Efficacy report (NCI-9653; 1UM1CA186717, NO1-CM-2011-00038)
Authors: S. Sadeghi, S. Groshen, R.A. Parikh, A. Mortazavi, T. Dorff, C. Hoimes, L. Doyle, D.I. Quinn, E. Newman, P. Lara
Journal: Annals of Oncology (2017)
Current Practice of State-of-the-Art Surgical Coronary Revascularization
Authors: Stuart J. Head, Milan Milojevic, David P. Taggart, John D. Puskas
Journal: Circulation (2017)

Coronary artery bypass grafting remains one of the most commonly performed major surgeries, with well-established symptomatic and prognostic benefits in patients with multivessel and left main coronary artery disease. This review summarizes current indications, contemporary practice, and outcomes of coronary artery bypass grafting. Despite an increasingly higher-risk profile of patients, outcomes have significantly improved over time, with significant reductions in operative mortality and perioperative complications. Five- and 10-year survival rates are ≈85% to 95% and 75%, respectively. A number of technical advances could further improve short- and long-term outcomes after coronary artery bypass grafting. Developments in off-pump and no-touch procedures; epiaortic scanning; conduit selection, including bilateral internal mammary artery and radial artery use; intraoperative graft assessment; minimally invasive procedures, including robotic-assisted surgery; and hybrid coronary revascularization are discussed.
Recent syphilis trends in Belgium and enhancement of STI surveillance systems
Authors: A Sasse, A Defraye, G Ducoffre
Journal: Eurosurveillance (2004)

Over the past five years, a series of syphilis outbreaks mainly occurring among gay men have been observed in Europe. One of these outbreaks was reported in the city of Antwerp, Belgium, during the first quarter of 2001. This outbreak is still ongoing in 2004. Furthermore, active syphilis diagnoses reported by the Sentinel Laboratory Network rose by 89% in the country during the fourth quarter of 2003. An increase in Brussels was also observed during the same quarter (+300%; 24 cases reported). Overall, the sentinel network of clinicians reported that 93.4% of patients were male; among them, 79.9% were men having sex with men (MSM). The overall proportion of patients co-infected with HIV was 50.5% (MSM: 58.6%; male heterosexuals: 23.8%; females: 8.3%); 76.1% of co-infected patients were already aware of their HIV infection at the time they were diagnosed with syphilis.
Utilization, Cost, and Outcome of Branded vs Compounded 17-Alpha Hydroxyprogesterone Caproate in Prevention of Preterm Birth
Authors: Inbar Fried, Andrew L. Beam, Isaac S. Kohane, Nathan P. Palmer
Journal: JAMA Internal Medicine (2017)

This study compares the utilization, cost, and outcome data from an insurance claims database to determine the difference in treatment efficacy between the branded and compounded versions of 17-alpha hydroxyprogesterone caproate.
GW28-e1181 Patients with atherosclerotic renal artery stenosis treated with percutaneous transluminal renal artery stenting for clinical efficacy in a single center
Authors: Tienan Zhou, Wang XiaoZeng, Liu LiWen, Han YaLing, Jing QuanMin, Zhao Xin, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia
Authors: Brenton G. Mar, S. Haihua Chu, Josephine D. Kahn, Andrei V. Krivtsov, Richard Koche, Cecilia A. Castellano, Jacob L. Kotlier, Rebecca L. Zon, Marie E. McConkey, Jonathan Chabon, Ryan Chappell, Peter V. Grauman, James J. Hsieh, Scott A. Armstrong, Benjamin L. Ebert
Journal: Blood (2017)
Emergencia de infecciones por SARM en caballos en un hospital veterinario : caracterización de las cepas y comparación con cepas humanas
Authors: C Cuny, J Kuemmerle, C Stanek, B Willey, B Strommenger, W Witte
Journal: Eurosurveillance (2006)

Los Staphylococcus aureus resistentes a la meticilina (SARM) estan volviendose un problema de salud publica emergente en el mundo entero, al no estar asociados unicamente a infecciones nosocomiales. Excepto por algunas publicaciones recientes de infecciones en gatos, perros y caballos, son escasas las descripciones de infecciones por SARM en animales de compania. El articulo siguiente describe los resultados de infecciones por SARM en caballos en un hospital veterinario de Europa central.
Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial
Authors: Abhinav Sharma, Jennifer B. Green, Allison Dunning, Yuliya Lokhnygina, Sana M. Al-Khatib, Renato D. Lopes, John B. Buse, John M. Lachin, Frans Van de Werf, Paul W. Armstrong, Keith D. Kaufman, Eberhard Standl, Juliana C.N. Chan, Larry A. Distiller, Russell Scott, Eric D. Peterson, Rury R. Holman
Journal: Diabetes Care (2017)

We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome.A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patient-years [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). The most common CV death was sudden death (n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke (n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) (n = 63, 12% of CV death). The most common non-CV death was malignancy (n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057).In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories.
Effect of lateral lymph node dissection for lower rectal cancer: An ad hoc analysis of the ACTS-RC randomized clinical trial
Authors: E. Oki, M. Shimokawa, A. Murata, T. Takahashi, K. Maeda, T. Kusumoto, Y. Munemoto, K. Ando, R. Nakanishi, M. Sugiyama, Y. Nakashima, H. Saeki, S. Saji, Y. Maehara
Journal: Annals of Oncology (2017)
Abstract 15988: S-wave as a Sensitive Measurement of Left Ventricular Dysfunction in Pre-operative Aortic Insufficiency Evaluation
Authors: Louis Simard, Francois Dagenais, Lionel Tastet, Marie-Annick Clavel
Journal: Circulation (2016)

Introduction: Optimal timing for aortic valve replacement (AVR) in severe aortic insufficiency (AI) is still debated. Guidelines underline left ventricular dysfunction as documented by ejection fra...
Concurrent chemoradiotherapy with S-1 in elderly patients with esophageal cancer.
Authors: Lei Zhao, Xiaolong Fu, Jindong Guo
Journal: Journal of Clinical Oncology (2015)

e15074 Background: Up to now, management of elderly patients with esophageal cancer (EC) remains a therapeutic challenge and the most optimal treatment modalities are still being debated. A phase IIstudy was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 for elderly patients with EC. Methods: Patients with histologically proved EC of clinical stage Ⅱ-ⅣA，≥ 70 years of age with ECOG ≤ 2 and near-normal organ function were eligible. CCRT comprised a 2Gy per day radiotherapy up to a total dose of 50-60Gy over 5-6 weeks plus S-1 orally at 50mg/m2/d on day1-14, repeated every 21 days. After CCRT, oral S-1 was continued at least 4 cycles. Clinical response and toxicity of treatment were assessed. Overall Survival (OS) and Progression Free Survival (PFS) curves were plotted using the Kaplan-Meier estimator. Results: From Dec.2011 to Jun.2014, fifty elderly patients, 19(38.0%) with stage II, 21(42.0%) with stage III and 10(20.0%) with stage ⅣA, were enrolled. Patients ranged in age from 70-84 years (median 75 years). All patients completed CCRT with median total radiation dose of 60Gy/30fx, and 47(94.0%) of them received the prescribed dose. All enrolled patients received oral S-1 after CCRT (median: 8 cycles, range 4–16 cycles). Inevitable interruption of S-1 occurred in 3(6.0%) patients due to treatment related esophageal fistula. The most serious toxicities were grade 3 anorexia and esophageal pain. Hematologic toxicity was moderate. Esophageal fistula was observed in 5(10.0%) patients, 3 due to treatment toxicity during additive therapy of oral S-1 and 2 due to disease progression after the final cycle of oral S-1. Complete response(CR) rate was 20.0%, and objective response rate (ORR) was 88.0%. The median OS and PFS time were 18.0±2.3 months(95%CI,15.3-22.7) and 16.0±1.1 months (95%CI,13.9-18.1), respectively. One and 2-year survival rates were 72.4% and 36.1%, respectively. Conclusions: For elderly patients with EC, CCRT with S-1 showed good efficacy with acceptable toxicity, which could become an alternative to conventional therapy. But it merits further evaluation by prospective phase III randomized controlled trials.
Analyzing biomarkers of cancer immunotherapy (CIT) response using a real-world clinico-genomic database
Authors: G. Singal, P.G. Miller, V. Agarwala, G. Li, A. Gossai, L.A. Albacker, M.E. Goldberg, J. He, S. Frank, D. Bourque, I. Ivanov, D. Fabrizio, T. Caron, A. Parker, A. Guria, V.A. Miller, J.A. Elvin, J.S. Ross, A. Abernethy, P.J. Stephens
Journal: Annals of Oncology (2017)
Vigilância da encefalite transmitida por carraças na Europa e definição de casos
Authors: G Günther, L Lindquist
Journal: Eurosurveillance (2005)

O estudo feito por P Stefanoff e collegas [1] levanta dois problemas importantes sobre encefalites transmitidas por carracas (ETC) : a falta de uma definicao de casos aceita por todos e a qualidade da vigilância nacional das encefalites transmitidas por carracas. Idealmente, os casos declarados deveriam ser confirmados e os casos clinicos com uma doenca do sistema nervoso central (SNC) deveriam ser separados dos casos sem manifestacao neurologica. Na Europa, a vigilância da encefalite transmitida por carracas varia segundo os paises e nao e sempre obrigatoria. Os esforcos para chegar a um diagnostico, especialmente nas formas menos agudas e nas criancas sao variaveis, assim como o consciencia dessa doenca em paises pouco endemicos. A unica base estavel e adaptada para uma vigilância nacional sao os casos presentando uma doenca do SNC confirmada, embora, ao nivel individual, a imunidade ao virus da encefalite transmitada por carracas depois de uma doenca febril menos forte tenha um certo valor. A razao entre os casos “sem doenca neurologica” e os casos “com doenca neurologica” e, aproximativamente, tres, mas existem diferencas regionais na virulencia. Nao se conhece diferencas associadas com a idade.
Some mechanisms of increasing malignancy of B16/F10 melanoma in female mice with chronic pain
Authors: I.M. Kotieva, O.I. Kit, E.M. Frantsiyants, I.V. Kaplieva, L.K. Trepitaki, V.A. Bandovkina, N.D. Cheryarina, Y.A. Pogorelova, L.Y. Vladimirova
Journal: Annals of Oncology (2017)
Abstract 13871: Does Compliance With a Global Cpr Quality Benchmark Predict Survival From Out-Of-Hospital Cardiac Arrest?
Authors: Sheldon Cheskes, Rob Schmicker, Laurie Morrison, Tom Rea, Brain Grunau, Ian Drennan, Brian Leroux, Christian Vaillancourt, Terri Schmidtt, Allison Koller, Peter Kudenchuk, Tom Aufderheide, Heather Herren, Gary Vilke, Kate Flickinger, Mark Charleston, Ron Straight, Jamie Jasti, Jim Christenson
Journal: Circulation (2016)

Background: Measures of chest compression fraction (CCF), compression rate, compression depth and pre-shock pause have all been independently associated with improved outcomes from out-of-hospital (OHCA) cardiac arrest. However, it is unknown whether compliance with a global CPR quality benchmark, incorporating the aforementioned metrics, can predict OHCA survival. Methods: We performed a secondary analysis of prospectively collected data from the Resuscitation Outcomes Consortium Cardiac Arrest Epistry database. As per the 2015 American Heart Association (AHA) guidelines, high quality CPR was defined as CCF &gt; 0.8, chest compression rate 100-120/minute, chest compression depth 50-60 mm and pre-shock pause&lt; 10 seconds. To derive a global CPR quality benchmark, we created multiple models employing combinations of CPR metrics to assess relationships between CPR compliance and survival to hospital discharge. Multivariable logistic regression models controlling for age, gender, witnessed status, bystander CPR, location, presenting rhythm and site were used to assess the relationship between compliance with a global CPR quality benchmark, survival to hospital discharge and neurologically intact survival with MRS &lt; 2. Results: We analyzed CPR process data from 35,445 defibrillator records collected over a 4 year time frame ending in June 2015. Of the 35,445 records, 19,568 (55.2%) included compression depth. For the primary model (CCF, rate, depth), there was no improvement in survival from OHCA comparing resuscitations that met no CPR quality benchmarks (reference) to those who met all CPR quality benchmarks (OR 0.89; 95% CI: 0.47, 1.70) and those who met some of the CPR quality benchmarks (OR 0.71; 95% CI: 0.45, 1.13). Models combining CCF, rate, depth and pre-shock pause yielded similar results for both shockable and non- shockable presenting rhythms when controlling for Utstein variables. Conclusions: When modeled in combination and adjusting for other predictors of survival, a global CPR quality benchmark using the current AHA guidelines was not associated with improved survival from OHCA. Unmeasured confounders, unknown combinations of optimal CPR quality metrics or possible interactions may explain our study findings.
Natural history and prognostic factors of head and neck cancer patients with bone metastases: A retrospective Italian study
Authors: S. Grisanti, C. Bergamini, S. Bianchi, A. Baiguini, S. Vecchio, L.D. Locati, A. Bonetta, P.F. Conte, M. Airoldi, M. Merlano, P. Carlini, T. Ibrahim, C. Rossetto, P. Nicolai, R. Maroldi, S. Tonoli, P. Pronzato, S.M. Magrini, L. Licitra, A. Berruti
Journal: Annals of Oncology (2017)
Open Fluidics: A Cell Culture Flow System Developed Over Wettability Contrast‐Based Chips
Authors: Nuno M. Oliveira, Rui L. Reis, João F. Mano
Journal: Advanced Healthcare Materials (2017)

Abstract Biological tissues are recurrently exposed to several dynamic mechanical forces that influence cell behavior. On this work, the focus is on the shear stress forces induced by fluid flow. The study of flow‐induced effects on cells leads to important advances in cardiovascular, cancer, stem cell, and bone biology understanding. These studies are performed using cell culture flow (CCF) systems, mainly parallel plate flow chambers (PPFC), and microfluidic systems. Here, it is proposed an original CCF system based on the open fluidics concept. The system is developed using a planar superhydrophobic platform with hydrophilic paths. The paths work as channels to drive cell culture medium flows without using walls for liquid confinement. The liquid streams are controlled just based on the wettability contrast. To validate the concept, the effect of the shear stress stimulus in the osteogenic differentiation of C2C12 myoblast cells is studied. Combining bone morphogenic protein (specifically BMP‐2) stimulation with this mechanical stimulus, a synergistic effect is found on osteoblast differentiation. This effect is confirmed by the enhancement of alkaline phosphatase activity, a well‐known early marker of osteogenic differentiation. The suggested CCF system combines characteristics and advantages of both the PPFC and microfluidic systems.
CheckMate 577: A randomized, double-blind, phase 3 study of adjuvant nivolumab (nivo) or placebo in pts with resected esophageal (E) or gastroesophageal junction (GEJ) cancer.
Authors: Ronan Joseph Kelly, Albert C. Lockhart, Derek J. Jonker, Bohuslav Melichar, Thierry Andre, Ian Chau, Stephen John Clarke, James M. Cleary, Yuichiro Doki, Fabio A. Franke, Yuko Kitagawa, Christophe Mariette, Paola Catherine Montenegro, Guillermo Ariel Mendez, Marika Ciprotti, Markus H. Moehler
Journal: Journal of Clinical Oncology (2017)

TPS4131 Background: Expression of the PD-1 ligands PD-L1 and PD-L2 has been reported in ≈ 40% of pts with E/GEJ cancer and is associated with a poor prognosis. In a phase 3 trial, the PD-1 inhibitor nivo demonstrated an OS benefit vs placebo (HR, 0.63; P &lt; 0.0001), resulting in a 37% reduction in the risk of death and double the OS rate at 12 mo (27% vs 11%) in pts with advanced gastric (G)/GEJ cancer refractory to ≥ 2 lines of chemotherapy (Kang YK, et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). In this study, nivo was well tolerated, with a safety profile comparable with that of the placebo arm. These results indicate that nivo could be a new standard of care (SOC) for pts with heavily pretreated advanced G/GEJ cancer and provide a strong rationale to explore nivo in earlier lines of treatment for G/E/GEJ cancer. Currently, no effective adjuvant SOC is available after chemoradiotherapy (CRT) followed by resection for pts with E/GEJ cancer. This multinational, double-blind, phase 3 trial will evaluate nivo as an adjuvant therapy for pts with resected E/GEJ cancer (CheckMate 577; NCT02743494). Methods: In this study, an estimated 760 pts aged ≥ 18 years with stage II/III E/GEJ cancer are randomized to receive nivo or placebo. Prior to randomization, pts must have completed preoperative CRT followed by surgery and been diagnosed with residual pathologic disease after being surgically rendered free of disease with negative margins following complete resection. Pts with stage 4 resectable disease, cervical esophageal cancer, or those who have not received concurrent CRT prior to surgery are not eligible for study enrollment. Primary endpoints are OS and disease-free survival. Other key endpoints include the OS rate at 1, 2, and 3 years and safety. Clinical trial information: NCT02743494.
Autologous stem cell transplantation (ASCT) is safe and effective for the treatment of non-hodgkin lymphoma (NHL) in an elderly population of patients over 65 years old: A single center experience
Authors: M.P. Tardy, J. Viotti, A. Boscagli Melaine, A. Thyss, F. Peyrade, L. Gastaud
Journal: Annals of Oncology (2017)
Comparing KRAS mutation testing by pyrosequencing versus allele specific primary extension methods in colorectal cancer specimens.
Authors: Keeran Ravin Sampat, Nirali Patel, Allison Mary Deal, Karen E Weck, Bert H. O'Neil
Journal: Journal of Clinical Oncology (2013)

e14522 Background: KRAS mutation status is an important clinical variable for targeting treatment in metastatic colon cancer. Many community practices send out mutational analysis to laboratories which utilize allele specific primer extension (ASPE) to identify mutations in only codons 12 or 13 of the KRAS gene. Our institutional molecular pathology laboratory performs pyrosequencing (PS) of KRAS codons 12, 13, and 61 which can potentially identify more KRAS mutations. We undertook this study to determine whether there were analytical differences in the results for specific mutations between these techniques. Methods: We obtained 77 sets of paraffin slides from a local practice from patients with metastatic adenocarcinoma of the colon whose KRAS mutation status had previously been analyzed by ASPE. After macrodissection for tumor enrichment, DNA was extracted from unstained paraffin slides and analyzed for KRAS codon 12, 13, and 61 mutations using the PyroMark KRAS v2.0 test. The results of KRAS testing by PS were then compared to those by ASPE. Exact 95% confidence intervals are reported. Results: None of the patients with KRAS codon 12 or 13 mutations called by ASPE (0/77, 0% [0%-4.7%]) changed to wild-type (WT) upon retesting by PS methodology. However, six patients had a discordant result between their ASPE-based testing and PS-based testing (6/77, 7.8% [2.9%-16.2%]). Two patients had differences in the amino acid (AA) at codon 12 (2/77, 2.6% [0.3%-9.1%]). Three patients were found to have a codon 61 mutation (3/77, 3.9% [0.8%-11.0%]), including two patients who were called KRAS WT by ASPE (2/30, 7% [0.8%-22%]). Finally, one patient with a call of a codon 13 mutation by ASPE changed to WT by PS (1/77, 1.3% [0.0% - 7.0%]). Conclusions: Almost 8% of patients who had KRAS testing by PS had a discrepancy in results compared with commercial ASPE testing alone. Although ASPE appears to be very accurate in detecting KRAS mutations, it missed KRAS codon 61 mutations in about 4% of the samples tested. This may have some clinical impact as we learn more about this subgroup of patients in the future.