tbuckley/cabot-search huggingface dataset:
Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum
Authors: Li Liu, Fred K. Tabung, Xuehong Zhang, Jonathan A. Nowak, Zhi Rong Qian, Tsuyoshi Hamada, Daniel Nevo, Susan Bullman, Kosuke Mima, Keisuke Kosumi, Annacarolina da Silva, Mingyang Song, Yin Cao, Tyler S. Twombly, Yan Shi, Hongli Liu, Mancang Gu, Hideo Koh, Wanwan Li, Chunxia Du, Yang Chen, Chenxi Li, Wenbin Li, Raaj S. Mehta, Kana Wu, Molin Wang, Aleksander D. Kostic, Marios Giannakis, Wendy S. Garrett, Curtis Hutthenhower, Andrew T. Chan, Charles S. Fuchs, Reiko Nishihara, Shuji Ogino, Edward L. Giovannucci
Journal: Clinical Gastroenterology and Hepatology (2018)
P138Structural consequences of FLNC mutations, associated with cardiomyopathies
Authors: A Kiselev, S Tarnovskaya, D Frischman, A Kostareva
Journal: Cardiovascular Research (2018)

Introduction: FLNC gene (MIM #102565) encodes an actin-cross-linking protein filamin C which is mainly expressed in heart and skeletal muscle.Mutations in FLNC give rise to skeletal muscle diseases and all types of cardiomyopathies.In our study we aimed to analyze the published disease-associated variants in FLNC and performed structural analysis depending on the phenotype of cardiomyopathy and mechanism of the mutation.Methods: We created dataset with disease-related mutations in FLNC using data from the literature and publicly available databases Clinvar and SwissVar.Domain organization of a filamin-C protein sequence was performed using Pfam database.The atomic structure of the Ig-like domain of human filamin C (PDB ID: 2D7M) was used as a template to introduce the mutations.In silico visualization were conducted using the PyMol software.Results: We found 44 variants in human FLNC gene associated with restrictive cardiomyopathy, myofibrillar myopathy, left-dominant arrhythmogenic cardiomyopathy, hypertrophic cardiomyopathy, distal myopathy and dilated cardiomyopathy according to ClinVar database and published manuscripts.Structural analysis revealed that mutations leading to restrictive (RCM) and hypertrophic (HCM) cardiomyopathy are predominantly localized within immunoglobulin-like domains of filamin C in loops near the protein surface.These loops may participate in formation of interdomain interactions with neighbour Ig-like domains in the super-repeat segment of filamin C and with ligands.Most of HCM and RCM-associated mutations are point mutations while most of mutations leading to dilated or arrhythmogenic cardiomyopathy are "lost of function" truncation or splicing mutations.Conclusion: Mutations within loops in Ig-like domains of filamin C protein may disturb mechanical strength and flexibility leading to increased cellular stiffness and influencing the mechanical properties of cells.The structural consequences of the mutation are linked to the type of myocardial remodeling, thus, explaining the broad phenotype variability of filaminopathies.
Correlation between classical prognostic factors and overexpression of HER2 and HER3 in localized gastric cancer.
Authors: Jose Alejandro Perez-Fidalgo, Noelia Tarazona, Samuel Navarro, Fernando Lopez-Mozos, Roberto Marti, Susana Rosello Keranen, Desamparados Roda Perez, Cristina Mongort, Andres Cervantes-Ruiperez
Journal: Journal of Clinical Oncology (2012)

e14589 Background: Although HER2 overexpression has been identified as a predictive factor for targeted therapy in advanced gastric cancer (GC), little is known about its role in localized GC. Recent studies suggest that not only HER2 but also HER3 might have a role in prognosis in GC. Our study aimed to identify the prevalence of HER2 and HER3 overexpression in a series of localized GC and to describe correlations of these with traditional prognostic factors Methods: We performed a retrospective analysis of HER2 and HER3 overexpression in archived tumour samples in pts diagnosed with GC at stage I-III. HER2 was assessed with herceptest, (negative if 0 or 1+, or positive with 2+ or 3+). Staining of HER3 was determined with the Rajkumar score (HER3+ when score &gt; or = 8). Correlation between the HER receptors expression and the clinicopathologic parameters was statistically analyzed. Statistical analysis of the correlation of HER2 and HER3 with other variables was performed with chi-square test or with the Mann Witney U for continuous variables. Impact on survival was analysed with Kaplan-Meier and log-rank tests. Results: From Jan 2003 to Sep 2011, 125 patients with clinical stage I-III GC were included. Median age was 73 years (35-91) and most frequent location was antrum (47.2%). Up to 43.2% of the patients were treated with preoperative chemotherapy. HER2 was + in 18 patients (14.4%) and HER3 in 38 (30.4%). HER2 was more likely to be overexpressed in older patients (median age: 78.4 vs 68.4; p&lt;0.0001) and in low grade adenocarcinomas (grade 1-2: 13.8% vs grade 3: 1.1%; p=0.006). HER3 was more frequently overexpressed at advanced stages (I and IIA: 10.3% vs IIB and III: 20.3%; p=0.004) and in adenocarcinoma with intestinal subtype (intestinal: 21.4% vs difuse/mixed: 8.5%; p=0.03) or without evidence of signet ring cells (absent: 26.8% vs present: 4.1%; p=0.03) . HER2 and HER3 were significantly related (p=0.0012) with an OR of 3,52 times more frequently HER3+, if HER2 was +. No significant impact was shown in survival for either HER2 or HER3. Conclusions: HER2 and HER3 overexpression seems to identify a particular subgroup of patients with favourable classical prognostic factors.
Outcomes over time (1998-2009) of stage II colon cancer patients (pts) receiving adjuvant FOLFOX: Pooled analysis of 1,122 pts in the ACCENT database.
Authors: Mohamed E. Salem, Jun Yin, Richard M. Goldberg, Levi Pederson, Norman Wolmark, Steven R. Alberts, Julien Taieb, John Marshall, Sara Lonardi, Takayuki Yoshino, Rachel Kerr, Greg Yothers, Axel Grothey, Thierry Andre, Aimery De Gramont, Qian Shi
Journal: Journal of Clinical Oncology (2018)

728 Background: Adjuvant FOLFOX therapy for stage II patients remains controversial, and selection criteria are imprecise. We examined the trend of disease-free survival (DFS: time to recurrence or death, whichever occurs first); time to recurrence (TTR: time to recurrence, censored at death without recurrence); survival after recurrence (SAR); and overall survival (OS) of pts treated with FOLFOX over a ten-year period. Methods: Outcomes of pts with stage II colon cancer enrolled in 6 adjuvant trials receiving FOLFOX alone were analyzed. Pt enrollment period was dichotomized as old (1998 – 2003) vs. new era (2004 – 2009) based on the FDA approval date of bevacizumab. 3/5yr event-free rates were estimated using adjusted Kaplan-Meier methods. Outcomes were compared between the two eras by multivariate Cox model. To control for potential confounding effects, all analyses were adjusted for age, gender, performance score, T stage, number of lymph nodes (LNs) examined, tumor side, and histologic grade. Results: In total, 1,122 pts with stage II were identified; 71% and 29% were treated in the old and new era, respectively. Pts enrolled in the new era were significantly younger and more likely to have higher tumor-grade and right-sided tumors compared to old era. More pts in the new era (71%) had ≥12 LNs examined compared to the old era (53%). After adjusting for potential confounding effects, no difference in DFS, TTR, SAR or OS between old and new eras was found (Table). Although median SAR increased from 13.6 to 26 months over time, this was not statistically significant, likely due to lack of power. An increased TTR over time (HR adj. 0.41, p adj. = 0.002) was observed in pts with ≥12 LNs examined (3-yr TTR: 92% in old era vs. 96% in new era), but not pts with &lt;12 LNs examined (p interaction = 0.04). Conclusions: In stage II colon cancer pts who received adjuvant FOLFOX, no significant increase of DFS or OS was observed over time. However TTR was longer only in pts with ≥12 LNs examined. [Table: see text]
Abstract 14907: Minimally Invasive Mitral Valve Annuloplasty Confers a Long-Term Survival Benefit Compared With State-Of-The-Art Treatment in Heart Failure Patients With Functional Mitral Regurgitation
Authors: Martin Penicka, Martin Kotrc, Tomas Ondrus, Yujing Mo, Filip Casselman, Marc Vanderheyden, Guy Van Camp, Frank Van Praet, Jozef Bartunek
Journal: Circulation (2016)

Introduction:  Data comparing the outcome of the minimally invasive surgical mitral valve annuloplasty (MVA) of isolated functional mitral regurgitation (FMR) with the state-of-the-art standards of care in systolic heart failure are not available.   Hypothesis:  We tested the hypothesis that isolated MVA using the minimally invasive surgical approach will be independently associated with long-term survival benefit compared with the state-of-the-art conservative (CON) treatment in the propensity-matched high-risk patients with chronic systolic heart failure and symptomatic FMR.   Methods:  The study population consisted of 312 consecutive patients (age 68.6± 10.8 years, 65.2% males) with stable LV systolic dysfunction, symptomatic FMR and previous heart failure hospitalization, who were followed in the heart failure clinic. A total of 158 patients underwent undersized MVA and 158 propensity-score matched patients were treated conservatively. A concomitant MAZE was performed in 53 (34%) patients.   Results:  In the MVA group, the periprocedural and the 30-day mortality were 1.3% and 5.7%, respectively. During the median follow-up of 6.3 years (IQR 3.5-8.2 years) a total of 12 (23%), 51 (49%) and 94 (60%) died in the MVA with MAZE, MVA without MAZE and the CON group, respectively (p   Conclusions:  In high-risk heart failure patients with symptomatic FMR, minimally invasive MVA, in particular in combination with MAZE, confers an independent long-term survival benefit compared with the state-of-the-art treatment.
Are peripheral blood eosinophil counts a guideline for omalizumab treatment? STELLAIR says no!
Authors: William W. Busse
Journal: European Respiratory Journal (2018)

Biologics for the treatment of severe asthma are assuming an ever expanding and important role to gain disease control when current therapeutics are not effective [1, 2]. Although the number of asthma patients with severe disease is relatively small, 10–15%, when compared to the overall prevalence of asthma, the burden of disease in this group is large from many perspectives including compromises to lifestyle, risks for recurrent and severe exacerbations, hospitalisations, unscheduled care needs, potential for adverse effects from medications, and medical costs. Therefore, severe asthma carries a dominant disease burden for the affected patient [3, 4]. Response to omalizumab is not dependent on peripheral blood eosinophil values <http://ow.ly/J7KT30jOlYC>
Improvement of carcinoid syndrome (CS) symptoms and quality of life (QoL) in CS patients treated with somatostatin analogs (SSAs): Results from longitudinal patient surveys.
Authors: Daniel M. Halperin, Lynn Huynh, Jennifer L Beaumont, Beilei Cai, Rachel Bhak, Sahil Narkhede, Mei Sheng Duh, Maureen Neary, David Cella
Journal: Journal of Clinical Oncology (2018)

400 Background: Limited information is available on the longitudinal impact of CS symptoms and QoL in CS patients (pts) who received SSAs in real-world setting. This study aimed to examine change in CS symptoms and QoL in CS pts treated with SSAs using the validated FACT-G instrument. Methods: Pts with CS symptoms in the US were recruited through an advocacy group to complete a two-part, anonymous online survey. Time point 1 (T1) survey was fielded from July-October 2016 and time point 2 (T2) was administered 6 months later. Eligible pts were ≥ 18 years old with CS symptoms and treated with SSA or non-SSA. Analyses were performed to assess change in FACT-G QoL scores between T1 and T2. Severity ratings of CS symptoms in the past month were classified as mild, moderate, severe, or not applicable. Duration of SSA treatment was categorized as ≤ 2, &gt; 2-5, and &gt; 5 years. Results: Among 89 pts who completed T1 and T2 surveys, 98% were treated with SSA (T1 or T2; median duration of 5 years). Higher proportion of pts in T2 did not report diarrhea (16% vs. 7%, p &lt; 0.05) or flushing (28% vs. 18%, p &lt; 0.05) vs. T1. Among pts treated with SSAs for ≤ 2, &gt; 2-5 and &gt; 5 years, mean change in FACT-G total score was +3.7, 0.0, and -1.2, respectively. Pts treated with SSAs for ≤ 2 years showed a clinically relevant improvement in QoL on FACT-G by exceeding the minimal important difference (MID) of &gt; 3.0. Additionally, in a subgroup of pts who experienced improvement in flushing (N=17) and diarrhea (N=31), a mean change of +3.0 in FACT-G total score was observed for flushing, indicating better QoL, whereas a nominal mean change was reported for diarrhea. Pts whose flushing and diarrhea symptoms worsened had a mean change of -2.2 and -1.2 in FACT-G total score, respectively, showing worsened QoL. Conclusions: This longitudinal survey study showed that improvement in flushing resulted in positive benefit in QoL, while worsening of flushing/diarrhea resulted in decline in QOL. Improvement in CS symptoms and QoL was most pronounced in the early years after SSA treatment initiation. Less impact on change in QoL may be observed in later years possibly due to disease progression and late-effects of cancer treatment.
Unplanned hospitalizations among gastrointestinal cancer patients in the state of Texas.
Authors: Joanna-Grace Manzano, Ruili Luo, Linda S. Elting, Maria Suarez-Almazor
Journal: Journal of Clinical Oncology (2013)

6634 Background: Hospitalization rates and cost of care for patients with Gastrointestinal (GI) malignancies are among the highest in the spectrum of cancers. It is poorly understood if these are driven by planned or unplanned hospitalizations. Methods: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data to describe the patterns of unplanned hospitalization among GI cancer patients in Texas. Our outcome, unplanned hospitalization, was defined as any emergent or urgent admission. Prior comorbidities were assessed using a modified Charlson score. Data were collected for 2 years from date of cancer diagnosis. Modified Poisson regression model was used to identify factors associated with the outcome. Results: 30,199 patients aged &gt;66 years were included in the study. 25,096 patients had 70,256 in-patient claims. 53.6% of these claims were unplanned hospitalizations. The top 3 reasons for unplanned hospitalization were pneumonia, congestive heart failure and volume depletion. Unplanned hospitalization rates ranged from 57.9% (colon) to 67.4% (esophageal) among the different cancer types. After multivariate analysis, unplanned hospitalization was more likely among those with esophageal cancer (RR=1.15, CI 1.1-1.2), gastric cancer (RR=1.07, CI 1.04-1.11), pancreatic cancer (RR=1.04, CI 1.01-1.07) and rectal cancer (RR= 1.03, CI 1.00-1.06). Patients with regional and distant disease were at higher risk for unplanned hospitalization (RR=1.14, CI 1.11-1.16 and RR=1.13 CI 1.1-1.16 respectively), as well as those aged &gt;80 (RR=1.04 CI 1.01-1.06), of black race (RR=1.06, CI 1.02-1.09), and living in census tract with &gt;21% poverty level (RR=1.06 CI 1.03-1.09). Risk of unplanned hospitalization also increased with Charlson scores (p&lt;.0001). Conclusions: The majority of hospitalizations were unplanned. Top reasons for unplanned hospitalization were diagnoses that are considered potentially preventable, and should be a focus for intervention. The disparity in unplanned hospitalizations among blacks and those living in poverty-stricken areas warrants further investigation as to whether this finding correlates with timely access to outpatient care in this population.
Alternatively-Activated Macrophages Upregulate Mesothelial Expression of P-Selectin to Enhance Adhesion of Ovarian Cancer Cells
Authors: Molly J. Carroll, Kaitlin C. Fogg, Harin A. Patel, Harris B. Krause, Anne-Sophie Mancha, Manish S. Patankar, Paul S. Weisman, Lisa Barroilhet, Pamela K. Kreeger
Journal: Cancer Research (2018)

Abstract Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a coculture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAM) influence the adhesion of tumor cells to mesothelial cells. We found that AAM-secreted MIP-1β activates CCR5/PI3K signaling in mesothelial cells, resulting in expression of P-selectin on the mesothelial cell surface. Tumor cells attached to this de novo P-selectin through CD24, resulting in increased tumor cell adhesion in static conditions and rolling underflow. C57/BL6 mice treated with MIP-1β exhibited increased P-selectin expression on mesothelial cells lining peritoneal tissues, which enhanced CaOV3 adhesion ex vivo and ID8 adhesion in vivo. Analysis of samples from patients with HGSOC confirmed increased MIP-1β and P-selectin, suggesting that this novel multicellular mechanism could be targeted to slow or stop metastasis in HGSOC by repurposing anti-CCR5 and P-selectin therapies developed for other indications. Significance: This study reports novel insights on the peritoneal dissemination occurring during progression of ovarian cancer and has potential for therapeutic intervention. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3560/F1.large.jpg. Cancer Res; 78(13); 3560–73. ©2018 AACR.
Finding the Right Balance
Authors: Birgitte Brandstrup
Journal: New England Journal of Medicine (2018)

When I was a young resident in the 1990s, surgical patients received so much intravenous saline on the day of surgery that they often gained 4 to 6 kg, and by postoperative day 2 or 3, pulmonary congestion and cardiac arrhythmias were commonplace. That was the basis for a 2003 trial of restrictive versus standard fluid therapy,1 which aimed to answer a simple question: Was so much fluid (and the ensuing tissue edema) beneficial for wound healing and cardiopulmonary function? That study, which enrolled 172 patients undergoing colorectal resection, showed that fluid overload and fluid retention were not beneficial; the . . .
Peanut lipids display potential adjuvanticity by triggering a pro-inflammatory response in human keratinocytes
Authors: C. Palladino, M. S. Narzt, M. Bublin, M. Schreiner, P. Humeniuk, M. Gschwandtner, C. Hafner, W. Hemmer, K. Hoffmann‐Sommergruber, M. Mildner, O. Palomares, F. Gruber, H. Breiteneder
Journal: Allergy (2018)
Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO
Authors: C. Cremolini, C. Antoniotti, S. Lonardi, F. Bergamo, E. Cortesi, G. Tomasello, R. Moretto, M. Ronzoni, P. Racca, F. Loupakis, A. Zaniboni, G. Tonini, A. Buonadonna, F. Marmorino, G. Allegrini, C. Granetto, G. Masi, V. Zagonel, E. Sensi, G. Fontanini, L. Boni, A. Falcone
Journal: Annals of Oncology (2018)

Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent.In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab.Tumors were defined as right-or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively.Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis.Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.Results: Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients.Patients with right-sided tumors (N ¼ 173) presented shorter OS [23.7 versus 31.0 months, HR ¼ 1.42 (95% CI 1.09-1.84),P ¼ 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR ¼ 1.24 (95% CI: 0.98-1.56),P ¼ 0.083] than those with left-sided tumors (N ¼ 185), but these associations were no longer evident when adjusting for RAS and BRAF status.Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR ¼ 0.59 versus 0.89, P for interaction ¼ 0.099) and OS (HR ¼ 0.56 versus 0.99, P for interaction ¼ 0.030) and this advantage was independent of their RAS and BRAF status.Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status.Trial registration: clinicaltrials.govidentifier NCT00719797.
Nationwide survey on the use of horse antithymocyte globulins (ATGAM) in patients with acquired aplastic anemia: A report on behalf of the French Reference Center for Aplastic Anemia
Authors: Régis Peffault de Latour, Reza Tabrizi, Ambroise Marcais, Thierry Leblanc, Thierry Lamy, Mohamad Mohty, Suzanne Tavitian, Charlotte Jubert, Marlène Pasquet, Claire Galambrun, Stéphanie Nguyen, Jean Yves Cahn, Thorsten Braun, Eric Deconinck, Jacques Olivier Bay, Flore Sicre de Fontbrune, Fiorenza Barraco, Gérard Socié
Journal: American Journal of Hematology (2018)

Abstract Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first‐line treatment of severe AA. The French Health Agency (ANSM) permitted a patient‐named authorization for temporary use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received antithymocyte globulins (ATGAM) plus CSA as first line treatment ( n = 379; 81.5%), or for refractory ( n = 26) or relapsed disease ( n = 33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty‐five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5 × 10 9 /L, male gender and longer delay between diagnosis and hATG (&gt;6 months period). This study does illustrate the results of ATGAM with CSA in a true‐life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT.