tbuckley/cabot-search huggingface dataset:
A prospective analysis of surgery and survival in stage IV breast cancer (TBCRC 013).
Authors: Tari A. King, Jaclyn Lyman, Mithat Gonen, Sylvia Reyes, Eun-Sil Shelley Hwang, Hope S. Rugo, Minetta C. Liu, Judy Caroline Boughey, Lisa K. Jacobs, Kandace P. McGuire, Anna Maria Storniolo, Claudine Isaacs, Ingrid M. Meszoely, Catherine H. Van Poznak, Gildy Babiera, Larry Norton, Monica Morrow, Antonio C. Wolff, Eric P. Winer, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2016)

1006 Background: TBCRC 013 is a multicenter prospective registry study evaluating the role of surgery for the primary tumor in de novo Stage IV disease. Methods: From 7/09-4/12, 127 pts from 14 sites were enrolled in 2 cohorts (A: Stage IV with intact primary (n = 112); B: metastases within 3 mos of primary surgery (n = 15)). All patients received 1st-line systemic therapy per treating physician. In Cohort A, patients classified as responders to 1st-line therapy (partial, complete, or stable distant disease) were referred to discuss elective surgery. Patient and tumor characteristics, response to systemic therapy and surgery of the primary tumor were correlated with 3yr overall survival (OS) using log rank, Kaplan Meier and Cox regression. Results: Among 112 pts in Cohort A, median pt age was 51yrs (21-77), median primary tumor size 3.2cm (0.8-15cm), median follow-up 54 mos (range 34-78). Subtypes were ER+HER2-, 71 (63%); ER+HER2+, 24 (21%); ER-HER2+, 9 (8%); ER-HER2-, 8 (7%). 3yr OS was 70% (95%CI, 63-79). 94 (85%) patients were classified as responders; 3 yr OS responders vs. non-responders, 78% (95%CI,70-87) vs 24% (95%CI,10-55), p < 0.001. Among responders, 39 (41%) chose surgery with no impact on 3y OS (77% with vs 76% without surgery, Table). Patients who chose surgery had larger tumors (3.8cm vs 3.2cm, p = 0.01), were more likely to have single organ metastatic disease (77% vs 41%, p = 0.001) and to have received 1st-line chemotherapy (39% vs 17%, p = 0.002). Among responders, surgery was not associated with improved survival for any subtype (ER+HER2-, p = 0.37; ER+HER2+, p = 0.07; ER-HER2+, p = 0.51; ER-HER2-, sample too small). Conclusions: In this prospective registry study of de novo Stage IV breast cancer, 3yr OS is 70%. The majority of patients responded to 1st-line therapy and 3yr OS was far superior among responders than non-responders. Among responders, surgery did not impact OS irrespective of tumor subtype. These data suggest caution in selecting patients for local therapy outside of clinical trials. Clinical trial information: NCT00941759.Responders Surgery N Median Survival, mos (95%CI) 3yr OS (95%CI) p All N 51 71 (56-NR) 76 (66-89) 0.85 Y 39 77 (52-NR) 77 (65-91) ER+ N 46 71 (56-NR) 78 (67–91) 0.47 Y 34 77 (53-NR) 79 (67-94) HER2+ N 12 NR (NR-NR) 83 (65-100) 0.39 Y 15 77 (77-NR) 100 (100-100)
Dose-Finding Methods: Moving Away from the 3 + 3 to Include Richer Outcomes
Authors: Xavier Paoletti, Damien Drubay, Laurence Collette
Journal: Clinical Cancer Research (2017)

The most commonly used method for dose finding, the 3 + 3, has poor performance. New adaptive designs are more efficient. Nevertheless, they have reached a maximum performance level, and further improvement requires either larger sample sizes or outcomes measures richer than the simplistic severe toxicity measured at cycle 1. Clin Cancer Res; 23(15); 3977-9. ©2017 AACRSee related article by Yan et al., p. 3994.
Serotonin and catecholamines in the development and progression of heart valve diseases
Authors: Elliott Goldberg, Juan B. Grau, Jacqueline H. Fortier, Elisa Salvati, Robert J. Levy, Giovanni Ferrari
Journal: Cardiovascular Research (2017)

Heart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling. Clinical evidence has suggested a link between certain neurotransmitters and valvular diseases of the heart. The fenfluramine–phentermine appetite suppressants popular in the 1980s were linked to mitral valve dysfunction, and ergot-derived dopamine agonists for Parkinson's disease have been associated with an increased risk of mitral and aortic valve regurgitation. The effect does not appear to be limited to medications, as valvular pathologies have also been observed in patients with carcinoid tumours of serotonin-producing enterochromaffin cells. The role of neurotransmitter molecules in valve pathology has not been adequately characterized and may represent a target for future medical therapies. Here we present current evidence from both clinical and basic science suggesting a link between neurotransmitters and HVDs, opening the door to future research in this area.
Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes
Authors: Michela Sica, Tommaso Rondelli, Patrizia Ricci, Maria De Angioletti, Antonio M. Risitano, Rosario Notaro
Journal: Journal of Hematology & Oncology (2017)

C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding.To investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway.When RBCs from untreated patients were exposed in vitro to activated complement in the context of C5-blockade, there was the prompt appearance of a distinct C3+ PNH RBC population whose size increased with time and also with the rate of complement activation. Eventually, all PNH RBCs become C3+ to the same extent, without differences between old and young (reticulocytes) PNH RBCs.This study indicates that the distinct (C3+ and C3-) PNH RBC populations are not intrinsically different; rather, they result from a stochastic all-or-nothing phenomenon linked to the time-dependent cumulative probability of each individual PNH red cell to be exposed to levels of complement activation able to trigger C3 binding. These findings may envision novel approaches to reduce C3 opsonization and the subsequent extravascular hemolysis in PNH patients on eculizumab.
Impact of switching to high deductible insurance on initiation and discontinuation of hormonal therapy among patients with early breast cancer.
Authors: Christine Y. Lu, Anita K. Wagner, Fang Zhang, Larissa Nekhlyudov, Dennis Ross-Degnan, James Frank Wharam
Journal: Journal of Clinical Oncology (2016)

552 Background: High-deductible health plans (HDHPs) requiring substantial out-of-pocket costs for most services might reduce appropriate health care. This study examined the impact of modern HDHPs on use of adjuvant hormonal therapy, which is a fundamental treatment for secondary prevention in patients with breast cancer. Methods: We studied 970 women with newly diagnosed early breast cancer who were insured by employers that mandated a transition from low-deductible ( < = $500) to high deductible ( > = $1,000) coverage and 11,155 contemporaneous patients whose employers offered only low-deductible plans. We propensity-score matched patients transitioning to HDHPs with contemporaneous patients whose employers offered only low-deductible coverage. Measures were time to initiation of adjuvant hormonal therapy and time to discontinuation of therapy (60-day gap in treatment). We used survival analysis to estimate changes in outcomes. Results: Prior to the HDHP-switch, time to initiation was similar between HDHP members and controls as expected with and without chemotherapy. Following the HDHP-switch, HDHP members had a higher likelihood of initiation (HR = 1.21 [0.96, 1.53]) compared to controls among members used chemotherapy, but a similar likelihood of initiation (HR = 1.05 [0.87, 1.25]) among those without chemotherapy. Among the pre-HDHP switch individuals who initiated hormonal therapy, time to discontinuation was similar between HDHP members and controls as expected. Among post-HDHP-switch individuals, HDHP members again had a similar risk of discontinuation (HR = 0.89 [0.69, 1.16]). Conclusions: In this rigorous, natural experimental study of a large population of incident breast cancer women, we did not detect reductions in initiation of hormonal therapy or a higher risk of discontinuation of these treatments among HPHD members. Further studies should examine HDHP effects among vulnerable subgroups such as those with low income, racial/ethnic minorities, and individuals covered by the subtype of HDHPs that requires full drug cost-sharing.
Androgen receptor in triple negative breast cancer: Expression and its clinic-pathological feature.
Authors: Mohamed Reda Kelany, Thanaa El-helal, Dalia Abd-Elghany El Khodary, Dalia Ali, Hager Ibrahim El-Ghazawy, Fatma Sayed, Mohamed Alorabi, Lamiaa Eid Abdallah
Journal: Journal of Clinical Oncology (2016)

e12567 Background: concern is now focused in the prognostic and predictive value of androgen receptor (AR) in breast cancer. Its expression and effect are variable and may depend on co-expression of estrogen receptor. The purpose of this study to investigate the expression of AR and its clinic-pathological feature in triple negative breast cancer. Methods: this retrospective study included 65 patients with TNBC. Who were treated in Ain Shams university hospital from January 2010 to December 2012 .paraffin blocks were retrieved and correlation between AR expression using immunohistochemistry and patient's clinico- pathological variables as well as survival . The cut-off value for AR expression was > /10% nuclear-stained tumor cells .chisquare test were chosen to determine the differences among variables. Results: AR expression was found in 29.2% (19/65) of TNBCs. Positive expression of AR showed significant correlation with nodal negative disease (p < 0.027). multivariate analysis indicated that AR was a significant independent prognostic factor for 2-year and 3-year DFS was 57.9% and 31.6% respectively with (P = < 0.013, Cl 95% 11.608–8.25) and for OS at 2-year and 3-year was 52.6% and 42.1(P = 0.011, Cl 95% 13.99–12.58). Conclusions: In our study AR-expressing TNBCs represent a favorable subgroup with better DFS and OS. Evaluation of AR status may provide a survival biomarker in patients with TNBC. Clinical trial information: 000017585.
Non-Invasive Genetic Profiling Is Highly Applicable in Multiple Myeloma (MM) through Characterization of Circulating Tumor Cells (CTCs)
Authors: Leire Burgos, Diego Alignani, Juan-Jose Garces, Lourdes Ortiz, Tomas Jelinek, Victor Segura, Luzalba Sanoja, Maria-Jose Calasanz, Xabier Agirre, Felipe Prosper, Paula Rodriguez-Otero, Rafael Rios, Joaquin Martinez-Lopez, Luis Palomera, Maria Teresa Zudaire, Rafael Del Orbe, Jacques J.M. van Dongen, Alberto Orfao, Bruno Paiva, Jesus San Miguel
Journal: Blood (2016)
The effects of prior concussion and contact sport participation on the brain
Authors: Nathan Churchill, Michael Hutchison, Tom A Schweizer
Journal: British Journal of Sports Medicine (2017)

Objective there is currently limited information on the neurobiological effects of contact sport participation, and interactions with history of concussion. The goal of this study is to examine the interactions between history of concussion and contact sport participation, using biomarkers of cerebral metabolites, brain function, and white matter microstructure. Design cross-sectional study. Setting sport medicine clinic, affiliated with inter-university sport program (secondary care). Participants 43 athletes without concussion in the past 6 months were recruited, including 22 athletes without prior concussion (13 non-contact, 9 contact; 11 female) and 21 athletes with a history of concussion (13 non-contact, 8 contact; 11 female). Outcome measures Magnetic Resonance Imaging (MRI) was used to measure brain biomarkers: MRI spectroscopy to evaluate cerebral metabolites; functional MRI to assess brain function; diffusion tensor imaging for white matter microstructure. Main results athletes in contact sports with prior concussion showed significant differences in brain structure and function, relative to athletes in non-contact sports, and those in contact sports without prior injury. This included significantly elevated glutamate ratios, decreased functional connectivity of the visual and motor systems, and increased fractional anisotropy of white matter. Conclusions This study provides the first multi-modal MRI data showing altered brain structure and function in athletes with a history of concussion and interactions with contact sport participation. These findings provide strong preliminary evidence that athletes in contact sports may be more vulnerable to the long-term effects of sport concussion. Competing interests None.
Computing patient data in the cloud: practical and legal considerations for genetics and genomics research in Europe and internationally
Authors: Fruzsina Molnár-Gábor, Rupert Lueck, Sergei Yakneen, Jan O. Korbel
Journal: Genome Medicine (2017)

Biomedical research is becoming increasingly large-scale and international. Cloud computing enables the comprehensive integration of genomic and clinical data, and the global sharing and collaborative processing of these data within a flexibly scalable infrastructure. Clouds offer novel research opportunities in genomics, as they facilitate cohort studies to be carried out at unprecedented scale, and they enable computer processing with superior pace and throughput, allowing researchers to address questions that could not be addressed by studies using limited cohorts. A well-developed example of such research is the Pan-Cancer Analysis of Whole Genomes project, which involves the analysis of petabyte-scale genomic datasets from research centers in different locations or countries and different jurisdictions. Aside from the tremendous opportunities, there are also concerns regarding the utilization of clouds; these concerns pertain to perceived limitations in data security and protection, and the need for due consideration of the rights of patient donors and research participants. Furthermore, the increased outsourcing of information technology impedes the ability of researchers to act within the realm of existing local regulations owing to fundamental differences in the understanding of the right to data protection in various legal systems. In this Opinion article, we address the current opportunities and limitations of cloud computing and highlight the responsible use of federated and hybrid clouds that are set up between public and private partners as an adequate solution for genetics and genomics research in Europe, and under certain conditions between Europe and international partners. This approach could represent a sensible middle ground between fragmented individual solutions and a "one-size-fits-all" approach.
Evaluation de la taille des polyad nomes coliques en dysplasie de haut grade (DHG) et carcinome in situ (CI): étude prospective à propos de 113 polypes
Authors: M Happi Nono, JC Letard, T Barrioz, A Verneau, P Lantier, P Debiais, P Babin
Journal: Endoscopy (2005)

But Le polype adénomateux est à l'origine de la plupart des cancers colo-rectaux. La filiation adénome – cancer est bien établie; elle passe par des dysplasies de degré croissant et leur risque de cancérisation est proportionnel à la taille du polype.
A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy
Authors: Zhangyuan Kong, Ping Qin, Shan Xiao, Hai Zhou, Hong Li, Renchi Yang, Xiaofan Liu, Jianmin Luo, Zhichun Li, Guochao Ji, Zhongguang Cui, Yusheng Bai, Yuxia Wu, Linlin Shao, Jun Peng, Jun Ma, Ming Hou
Journal: Blood (2017)
The effect of recombinant tumor necrosis factor-thymosin-α1 on angiogenesis in the tumor and the effectiveness of neoadjuvant chemotherapy in locally advanced breast cancer.
Authors: Liubov Yu Vladimirova, Oleg Ivanovich Kit, Evgeniya M. Nepomnyashchaya, Natalia Podzorova, Inna Arnoldovna Novikova, Elena Petrovna Ulianova, Galina I. Zakora, Elena Bondarenko, Yury Valentinovich Przhedetskiy
Journal: Journal of Clinical Oncology (2016)

1030 Background: There is a few data on tumor necrosis factor drugs used in neoadjuvant treatment in locally advanced breast cancer (LABC) patients. Many studies demonstrate the importance of angiogenesis in the development of carcinomas, whereas there is a little known about the influence of recombinant protein of tumor necrosis factor-thymosin-alpha1 (TNF-T) on angiogenesis in ВС. The aim of the study was to investigate markers of angiogenesis and vascular proliferation in the tumor and to evaluate the efficacy of TNF-T in the neoadjuvant treatment of LABC. Methods: Eligibility criteria included LABC of IIB-IIIB stages, ECOG ≤ 1, adequate liver, kidney and bone marrow function, no brain metastases. Recombinant protein of TNF-T 200000 IU was used peritumorally (injected around the tumor) on D1-5 (30 min before cytostatics injection), combined with standard FAC or PA regimens. The factors of angiogenesis CD31 and CD34 were studied in trephine-biopsy specimens before treatment and in postsurgical biopsies of the tumor after TNF-T courses. Results: 82 women were recruited between April 2012 – October 2013 (mean age 53.3±1.1 years). Group A (30 pts) received recombinant protein of TNF-T combined to PA (17) and FAC (13) up to 6 courses. Group B (52pts) received standard PA (21) and FAC (31). Tumor response (TR) in Group A was 80% and in Group B 71.9% (p < 0.05), including CR 15% and 6.25%, correspondingly (p < 0.05). The number of vessels of the microcirculation in sight was for CD31: 5,9±0,34 before treatment and 2,24±0,35 after treatment (p < 0.05); CD34: to 6.88±1.07 and 2,75±0,72, respectively (p < 0.05). All patients in Group A were operated successfully, no postoperative complications connected with TNF-T use were observed. By the time of abstract submission OS in Group A was 35.6±1.2mos, in Group B was 34.1±1.1mos; EFS in Group A was 33.5±1.1mos, in Group B was 28.7±1.2mos (p < 0.05). Conclusions: TNF-T injected peritumorally allows to increase the antitumor activity of cytostatics (pCR) which is of great importance for survival inLABC. The data acquired in the biopsies show that the recombinant protein of TNF-T has the suppressive effect on angiogenesis.
Trends in female breast cancer in the republic of Mauritius over past two decades.
Authors: Shyam Shunker Manraj, Nilufer Jasmine Selimah Fauzee, Anil Mohith, Clement Adebamowo
Journal: Journal of Clinical Oncology (2014)

e11560 Background: The Republic of Mauritius is situated in the Indian Ocean with a racially mixed population of 1.3 million; life expectancy in 2012 is 77.1 years in females. Cardiovascular disease and diabetes are the leading cause of deaths and cancer ranks third representing 12% of deaths. Since 1989, a National Cancer Registry (NCR) is operational and has reached a population-based level (PBCR) since 2001. Methods: A retrospective epidemiological study on incidence and mortality of breast cancer (BC) starting from 1989 till 2012 was carried out. NCR Data have been retrieved and analysed by four-year periods. Cancer mortality statistics using ICD-9 and ICD-10 classification were obtained from Civil Status Office for the corresponding periods. Further data on hormone-receptor (ER/PR) status and survival were collected from the Central Health Laboratory and unique radiotherapy department (RT) of the island. Results: From 1989 till 2012, 5756 new cases of BC have been registered out of a total of 17,862 cancer cases in females and ASRW/105rates have increased from 22.9 for 1989-1992 to 49.0 for 2009-2012. For period 2009-2012, it represents the most common site in females 39.3% ahead of cervical cancer 7.9%. The mean age at diagnosis has increased from 51.1 years in 1989-1992 to 56.0 years in 2009-2012. BC was found to be more prevalent in urban areas compared to rural ones (observed over expected ratio: O/E=1.42). BC accounted for 25.6% of all cancer deaths in 2012 and the MI ratio (Mortality/Incidence) for 2009-2012 was 0.32. Concerning ER/PR status, out of 305 BC cases analysed in 2013, ER+/PR+ was 60%, ER+/PR- was 9.5%, ER-/PR+ was 4.3% and ER-/PR- was 24.9%. For patients treated by the RT department, the ten-year survival (2001-2011) according to stage at diagnosis was as follows: stage1 (83%), stage2 (79%), stage3 (79%) and stage4 (0%) respectively, with an overall survival rate of 71%. Conclusions: BC incidence shows a very significant increase over last two decades mimicking trends of prostate, endometrial and colorectal cancer in Mauritius. This situation warrants adequate preventive and curative strategies in the near future for the benefit of women in the island.
Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide
Authors: J. P. Thyssen, C. R. Hamann, A. Linneberg, T. M. Dantoft, L. Skov, G. H. Gislason, J. J. Wu, A. Egeberg
Journal: Allergy (2017)

Atopic dermatitis (AD) has been linked with psychiatric disease in adults. However, the exact relationship and its consequences have been insufficiently studied. Our aim of this study was to assess the association between depression, anxiety, and AD in adults and examine the risk of hospitalization and suicide.We utilized questionnaire data from a large general population study with data on social habits and psychiatric symptoms to compare prevalences of depression, anxiety, suicidal ideation, and anxiety attacks, in adults with and without a history of AD. Additionally, we used nationwide hospital/clinic registry and prescription data to examine the risk of anxiety and depression in Danish adults with mild and moderate-severe AD, as well as the risk of hospitalization and suicide.In the general population study, those with AD reported clinician-diagnosed depression and anxiety more often than non-AD subjects, and had an increased prevalence of suicidal ideation and depressive symptoms. In the health registry study, moderate-severe AD patients had increased risk of antidepressant and anxiolytic medication use, while patients with mild AD only had increased risk of anxiolytic medication use. There was no increased risk of hospitalization or outpatient contacts due to depression or anxiety, or risk of suicide in AD patients.Depression, anxiety, and suicidal ideation are more common among AD individuals, but do not lead to psychiatric consultations, hospitalization, or suicide.