tbuckley/cabot-search huggingface dataset:
Docetaxel, cyclophosphamide and trastuzumab as neoadjuvant chemotherapy in HER2-positive primary breast cancer.
Authors: Katsuhiko Nakatsukasa, Tetsuya Taguchi, Riho Sugimoto, Kouichi Sakaguchi, Tatsuya Kotani, Kenichirou Hukuda, Sadao Kawakami, Ikuya Hujiwara
Journal: Journal of Clinical Oncology (2015)

583 Background: The current standard treatment of primary systemic therapy (PST) in HER2+ breast cancer is anthracyclines and/or taxanes combined with trastuzumab which demonstrates high pathological complete response (pCR). The pCR is considered as a predictive marker of prognosis although results are slightly different depending on the hormone receptor status. The efficacy and tolerability of docetaxel, cyclophosphamide and trastuzumab (HER-TC) as neoadjuvant chemotherapy (NAC) remains unclear. We performed a prospective multicenter study of HER-TC NAC in HER2+ primary breast cancer. Methods: Eligible patients had HER2+ invasive breast cancer that measured more than 1cm, less than 7 cm and N0~N1 clinically between July 2011 and February 2014. Four cycles of HER-TC (6 mg/kg loading dose 8 mg/kg, 75 and 600 mg/m2) were administered intravenously every 3 weeks as NAC. We investigated the pCR of primary breast tumors; pCR was defined as no histological evidence of invasive carcinoma, or the appearance of only ductal carcinoma in situ. Cardiac toxic effects, defined as a decrease in left ventricular ejection fraction (LVEF), were assessed by echo-cardiography at baseline, at the completion of NAC. Results: 42 patients were enrolled. The completion rate for 4 cycles of HER-TC was 97.6 % (41 of 42). Relative dose intensity was 98.0 % for HER-TC therapy. Overall pCR rate was 43.9 % (18 of 41). pCR rate for patients with luminal HER2 (ER+, HER2+), and HER2 enriched ( ER-, HER2+ ) were 40.0 % (8 of 20), and 47.6 % (10 of 21), respectively. pCR was achived with about same probability in each subtype. Mean LVEF at baseline and, the completion of NAC were 66.1% and 64.8%, respectively. Conclusions: Four cycles of HER-TC might be one of the NAC options for HER2 positive breast cancer. There were no patients with decrease in LVEF during the treatment. Clinical trial information: UMIN000013263.
Safety of Anticoagulant Therapies for Treatment of Venous Thromboembolism in Patients with Cancer
Authors: Michael Streiff, Dejan Milentijevic, Keith McCrae, Daniel Yannicelli, Jonathan Fortier, Winnie Nelson, François Laliberté, Concetta Crivera, Patrick Lefebvre, Jeff Schein, Alok A. Khorana
Journal: Blood (2016)
The utility of individual baseline versus normative reference values for the scat3 following concussion in professional ice hockey players
Authors: Timo Hänninen, Jari Parkkari, Markku Tuominen, Grant L Iverson, Matti Vartiainen, Juha Öhman, Teemu M Luoto
Journal: British Journal of Sports Medicine (2017)

Objective To characterise whether individual SCAT3 baseline scores are more useful than normative reference values following acute concussion. Design Prospective cohort. Setting Finnish professional male ice hockey league. Participants SCAT3 baseline testing has been mandatory in the league since 2013. The league recommends day of injury testing for all players with suspected concussion. Of the reported day of injury SCAT3s, between seasons 2013–2016, a total of 29 concussions were confirmed by the teams’ medical staff. Outcome measures Measures included: the individual baseline and day of concussion scores of the injured players; The league’s normative reference values [based on 2013–2014 preseason baselines (n=304)]; and the limits of normal variation on SCAT3 [based on league’s preseason baselines 2013–2014 and 2014–2015 (n=179)]. The post-injury performance was ruled as abnormal if (i) the player scored within the worst 10th percentile of the normative reference values or (ii) the score differed from the player’s own baseline more than the cut offs for 90% normal variation. Main results The percentages of the players who performed abnormally on post-concussion testing (scores compared to individual baseline vs. normative reference values) were as follows: Symptoms: 96% vs. 100%; SAC: 31% vs. 22%; M-BESS: 50% vs. 50%; Tandem gait: 18% vs. 29%; Coordination: 7% vs. 7%. Conclusions Post-concussion testing conducted with individual baseline seems to be as sensitive as assessment compared to normative reference values in acute concussion recognition. Symptoms were the most sensitive SCAT3 component. Competing interests Timo Hnninen, Markku Tuominen, Jari Parkkari, Matti Vartiainen, Juha hman, Teemu M. Luoto: None. Grant L. Iverson has been reimbursed by the government, professional scientific bodies, and commercial organisations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has not received research support from a test publishing company in the past 5 years.
Physical and psychosocial functioning of women and men after coronary artery bypass surgery
Authors: J. Z. Ayanian
Journal: JAMA (1995)

<h3>Objective.</h3> —To assess whether physical and psychosocial functioning differs between women and men after coronary artery bypass surgery. <h3>Design.</h3> —Observational cohort study. <h3>Setting.</h3> —Major teaching hospital. <h3>Patients.</h3> —A total of 454 consecutive patients who received coronary artery bypass surgery from June 1989 through March 1990. <h3>Main Outcome Measures.</h3> —Nurse reviewers collected data on the severity of coronary artery disease and coexisting illnesses from medical records. A mailed survey measuring instrumental activities of daily living (IADLs), social activities, mental health, and vitality was completed by 306 (70.2%) of 436 patients who were alive 6 months after surgery. Functioning on each scale was adjusted for age, marital status, education, severity of angina, recent myocardial infarction, congestive heart failure, and coexisting illnesses at the time of surgery. <h3>Results.</h3> —Before surgery, women were much more likely than men to have had class IV angina (50.9% vs 30.4%), a recent myocardial infarction (32.1% vs 18.0%), and congestive heart failure (34.0% vs 17.6%) (all<i>P</i>&lt;.002). On a range from 0 (severe impairment) to 100 (no impairment), adjusted postoperative functioning was equivalent for women and men in IADLs (86.7 vs 89.1), social activities (95.2 vs 95.3), mental health (72.6 vs 76.0), and vitality (58.1 vs 62.5) (all<i>P</i>&gt;.20). Women reported similar or greater adjusted improvements than men for IDALs (27.2 vs 19.6,<i>P</i>=.08), social activities (20.8 vs 8.0,<i>P</i>=.002), mental health (11.2 vs 5.7,<i>P</i>=.05), and vitality (22.2 vs 12.9,<i>P</i>=.04). <h3>Conclusions.</h3> —Women were more severely ill than men at the time of coronary artery bypass surgery, but women and men reported similar physical and psychosocial functioning 6 months after surgery. These findings demonstrate important functional benefits of this procedure among both women and men. (<i>JAMA</i>. 1995;274:1767-1770)
TRTH-08. HIGH GRADE NEUROEPITHELIAL TUMOR OF THE CENTRAL NERVOUS SYSTEM WITH BCOR ALTERATION IS SENSITIVE TO IGF1R INHIBITION
Authors: Claudia Paret, Alexandra Russo, Nadine Lehmann, Nora Backes, Lea Roth, Khalifa El Malki, Arthur Wingerter, Marie A Neu, Larissa Seidmann, Aslihan Gerhold-Ay, Wolfgang Wagner, Jörg Faber
Journal: Neuro-Oncology (2017)

High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity which was formerly diagnosed with diverse histological diagnoses, for example as ependymoma. This tumor predominantly affects children and has a dismal prognosis. No standard therapies for this entity exist so far. Recently we described the activation of the Sonic hedgehog (SHH) and the WNT signaling pathway in this tumor and described a primary cell culture (PhKh1) isolated from a skull metastasis of a seven years old patient. We also detected a high expression of IGF2, which is known to be required for SHH signaling in medulloblastoma. IGF2 signals through IGF1R leading to cell growth via the downstream PI3K/Akt pathway. In pediatric brain tumors high expression of IGF2 has been described in ependymoma and may acts as a molecular target. Here we analyzed the expression of IGF2 in our transcriptome data of 12 pediatric brain tumors patients (6 medulloblastoma, 2 glioblastoma, 2 anaplastic astrocytoma, 1 HGNET-BCOR and 1 ependymoma relapse). The highest expression of IGF2 was detected in the HGNET-BCOR and ependymoma samples. The high expression of IGF2 was maintained in the PhKh1 cell line and was similar to the expression detected in a primary cell culture isolated from the ependymoma relapse. Incubation with increasing concentrations of an antibody that blocks IGF1R resulted in a great reduction of the cell proliferation of the PhKh1 cell line but not of an IGF2-negative control cell line. In conclusion, the high expression of IGF2 may be a common feature of HGNET-BCOR and ependymoma and may represent a target for new approaches. Several monoclonal antibodies and TKIs for IGF1R are being tested in preclinical and early phase clinical studies and may become relevant in the management of this new and aggressive tumor entity.
HGG-18. GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS SHARE SEVERAL MOLECULAR FEATURES WITH THEIR PEDIATRIC COUNTERPARTS
Authors: Scott Ryall, Sunit Das, Uri Tabori, David Munoz, Cynthia Hawkins
Journal: Neuro-Oncology (2017)

The molecular features of both pediatric and adult gliomas have been extensively studied for their diagnostic and clinical value. However, a population-based characterization of the adolescent/young adult population (AYA) has not been well documented. It remains unclear whether the frequency and prognostic significance of common alterations in pediatric gliomas carry over to the AYA population. We assembled a cohort of 101 gliomas treated at St. Michael’s Hospital from which 86 samples had sufficient material for molecular characterization. MRI and pathology reviews confirmed accurate diagnosis. H3F3A, BRAF, and IDH1 mutations were detected using the Bio-Rad QX200 Droplet-Digital system. Our cohort consisted of 31 tumours diagnosed as low grade (23% grade I, 58% grade II, and 19% LGG, NOS) and 70 diagnosed as high grade (40% grade III, 59% grade IV, and 1% HGG, NOS). Median age of the patients was 29 years (18–39). Of the 86 tested for molecular alterations, 10 (12%) of the tumours tested positive for H3_K27M tumours, with a median age of 21.5 years (18–35). H3_K27M mutations occurred exclusively in midline tumours (10/32, 31%). K27M mutations were observed in both high and low grade tumours (7 and 3, respectively). BRAF_V600E was detected in 6 (7%) of patients with a median age of 26.5 years (18–37). BRAF_V600E mutations were detected in both midline and hemispheric tumours and across all histological grades. IDH1_R132H mutations were detected in 31 (36%) patients with a median age of 29 (21–39). IDH1 mutations appeared in both midline and hemispheric tumours and across all histologies. All mutations detected occurred mutually exclusive to one another. The work presented here shows the incidence of classically pediatric mutations in an AYA cohort. It is important that clinicians be aware that these mutations may be present in AYAs and may have an impact on their clinical course.
Клініко-лабораторні особливості стеатозу підшлункової залози у дітей з надлишковою вагою та ожирінням
Authors: N.Yu. Zavgorodnyaya, O.Yu. Lukianenko
Journal: GASTROENTEROLOGY (2017)

Актуальність. Неалкогольна жирова хвороба підшлункової залози — патологічний стан, тісно асоційований з ожирінням та іншими компонентами метаболічного синдрому. Клінічні прояви обумовлюються порушенням екзокринної функції залози, що супроводжується розвитком дисбіотичних змін та інтестинальних розладів. Мета. Вивчити клініко-лабораторні особливості стеатозу підшлункової залози у дітей з надлишковою вагою та ожирінням. Матеріали та методи. У 24 дітей з функціональними розладами шлунково-кишкового тракту визначали наявність стеатозу підшлункової залози за допомогою ультра­звукового дослідження. Для характеристики стану тонкокишкової мікробіоти проводили водневий дихальний тест з навантаженням глюкозою або лактозою. Виявлення стеатозу печінки проводили за допомогою транзієнтної еластрографії печінки з визначенням контрольованого параметра ультразвукового затухання. Розподіл за групами відбувся на підставі наявності стеатозу підшлункової залози: контрольну групу (S0) становили 12 пацієнтів без стеатозу підшлункової залози, основну групу (S+) — 12 пацієнтів зі стеатозом підшлункової залози. Результати. Стеатоз підшлункової залози у дітей з надлишковою вагою та ожирінням характеризувався неспецифічною клінічною картиною з переважанням диспептичних явищ. Встановлено, що у дітей основної групи спостерігалось зниження рівня амілази сироватки крові порівняно з конт­рольною групою (середнє значення (30,40 ± 12,45) ммоль/л в основній групі та (51,88 ± 19,81) ммоль/л у контрольній, p &lt; 0,05). Було виявлено, що у пацієнтів основної групи вірогідно частіше зустрічалась стеаторея (75 % хворих основної групи проти 33,3 % дітей контрольної групи, p &lt; 0,05). Стеатоз підшлункової залози у дітей був асоційований з розвитком синдрому надмірного бактеріального росту (50 % хворих основної групи проти 8,3 % дітей контрольної групи, р &lt; 0,05). Серед пацієнтів зі стеатозом підшлункової залози 41,6 % мали ознаки стеатозу печінки, в той час як панкреатичний стеатоз зустрічався у 62,5 % пацієнтів із неалкогольною жировою хворобою печінки. Діти зі стеатозом підшлункової залози мали помірне прискорення швидкості осідання еритроцитів (середній показник становив (16,6 ± 6,76) мм/год у пацієнтів основної групи проти (7,17 ± 3,18) мм/год у пацієнтів контрольної групи). Висновки. Панкреатичний стеатоз може виступати більш раннім маркером ектопічного накопичення жиру порівняно зі стеатозом печінки. Стеатоз підшлункової залози у дітей з надлишковою вагою та ожирінням характеризується наявністю низькорівневого системного запалення, диспептичних явищ, непрямих ознак зовнішньосекреторної недостатності залози та синдромом надмірного бактеріального росту.
CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury
Authors: Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R. Figliuolo, Thiago F. de Avelar Almeida, Patrícia T. Santana, Suellen D.S. Oliveira, Claudia L.M. Silva, Linda Feldbrügge, Eva Csizmadia, Richard D. Minshall, Maria Serena Longhi, Yan Wu, Simon C. Robson, Robson Coutinho-Silva
Journal: Journal of Hepatology (2017)
Day of injury dizziness is related to prolonged recovery following concussion
Authors: Teemu M Luoto, Timo Hänninen, Jari Parkkari, Markku Tuominen, Grant L Iverson, Matti Vartiainen, Juha Öhman
Journal: British Journal of Sports Medicine (2017)

Objective To examine the relation between day of injury concussion symptomology and prolonged recovery. Design Prospective cohort. Setting Finnish professional ice hockey league. Participants SCAT3 baseline and post-injury testing has been mandatory in the Finnish ice hockey league since 2013. Of the reported injuries, between seasons 2013-2016, all cases with a day of injury SCAT3 symptom scale completed were selected. The teams’ medical staff confirmed 28 concussions, which were assessed on the day of injury. Outcome measures The SCAT3 symptom scale was completed on the day of injury. All 22 symptoms were analysed separately. Team medical staff followed up all concussed players and the day of return to play (RTP) was recorder for each athlete. Concussion recovery was considered prolonged if the time of RTP was over 10 days. RTP was analysed as a continuous and a dichotomized variable. Main results All concussed players (n=28) were Caucasian. The average age was 26.4 years (SD=4.3). The mean Symptom Score was 12.1 (SD=4.3) and the Symptom Severity 26.4 (SD=13.5), respectively. The median time to RTP was 9 days (M=21, SD=47, range=4–248) with 36% of the players being out of play for more than 10 days. There was a significant correlation between Symptom Severity and RTP (p=0.046). Symptom Score was not related to RTP. Dizziness was the only symptom with a consistent statistical relation to longer RTP (Spearman rho=0.4, p=0.029; Mann-Whitney U=4.9, p=0.038; Binary univariate logistic regression: OR=2.6, p=0.04). Conclusions Acute day of injury dizziness was related to prolonged recovery following concussion. Competing interests Teemu M. Luoto, Timo Hnninen, Jari Parkkari, Markku Tuominen, Matti Vartiainen, Juha hman: None. Grant L. Iverson has been reimbursed by the government, professional scientific bodies, and commercial organisations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has not received research support from a test publishing company in the past 5 years. None.
Gas-filled microbubbles: Novel mucosal antigen-delivery system for induction of anti-pathogen's immune responses in the gut
Authors: Blaise Corthésy, Gilles Bioley
Journal: Gut Microbes (2017)

Despite important success in protecting individuals against many pathogenic infections, parenteral vaccination is not optimal to induce immunity at the site of pathogen entry, i.e. mucosal surfaces. Moreover, designing adequate delivery systems and safe adjuvants to overcome the inherent tolerogenic environment of the mucosal tissue is challenging, in particular in the gastrointestinal tract prone to antigen degradation. We recently demonstrated that intranasal administration of a Salmonella-derived antigen associated with gas-filled microbubbles induced specific Ab and T cell responses in the gut and was associated with a reduction in local and systemic bacterial load after oral Salmonella infection. Building on these promising data, the adequate choice of antigen(s) to be administered and how to make it suitable for possible human application are discussed. We additionally present novel data dealing with oral administration of microbubbles and describe research strategies to direct them to mucosal sampling/inductive sites.
Incidence and Prognostic Impact of Cytogenetics in Combination with Molecular Aberrations in Patients with Systemic Mastocytosis
Authors: Nicole Naumann, Mohamad Jawhar, Juliana Schwaab, Georgia Metzgeroth, Henning D Popp, Nada Khaled, Hans-Peter Horny, Karl Sotlar, Peter Valent, Claudia Haferlach, Gudrun Göhring, Brigitte Schlegelberger, Manja Meggendorfer, Nicholas C.P. Cross, Wolf-Karsten Hofmann, Andreas Reiter, Alice Fabarius
Journal: Blood (2016)
Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials
Authors: Martin Hale, James Wild, Jyotsna Reddy, Tadaaki Yamada, Juan Camilo Arjona Ferreira
Journal: The Lancet. Gastroenterology & hepatology (2017)
MEDU-25. THE EFFECTS OF CRANIAL RADIOTHERAPY-INDUCED VASCULAR INJURY ON BRAIN TISSUE STRUCTURE AND COGNITIVE FUNCTION IN CHILDREN WITH MEDULLOBLASTOMA
Authors: Melanie Morrison, Angela Jakary, Erin Felton, Sabine Mueller, Janine Lupo
Journal: Neuro-Oncology (2017)

INTRODUCTION: Cranial radiation therapy (CRT) remains an integral role in the treatment of pediatric medulloblastomas, despite its association with significant long-term effects including CRT-induced vascular injury and cognitive impairments. Manifestation of CRT-induced vascular injury including size-varying hemosiderin deposits in the form of cerebral microbleeds (CMBs), and changes in white matter integrity and cortical thickness can be detected with MRI as early as 8 months following treatment. Although vascular injuries have been previously related to cognitive decline in stroke and dementia, the underlying mechanisms driving these and CRT-associated cognitive deficits remain unclear. As current treatment strategies are improving the prognosis for children with medulloblastoma, identifying a link between CRT-induced injury and cognition is an important consideration for this group in determining the impact of treatment on development. METHODS: Ten pediatric medulloblastoma patients (age:10–24 years) treated with uniform, whole-supratentorial brain CRT 0.75–15 years prior, and 5 nonirradiated control patients (age:14–23 years) with posterior fossa tumors were scanned on a 7-Tesla system. High resolution T1-weighted anatomical and susceptibility-weighted vascular imaging were acquired along with multi-directional, multi-shell diffusion tensor imaging. A computerized cognitive battery (Cogstate) was employed to assess multiple domains of cognitive function. The spatial distribution of CRT-induced vascular injury was related to white-matter and cortical integrity, cognitive performance, and connectivity within cerebral networks. RESULTS: Patients in the control group did not develop any CMBs. The majority of CMBs in irradiated children were located in the frontal lobe. The level of injury was associated with deficits initially in working- and then in visual-memory as a function of time since CRT and poorer connectivity. CONCLUSIONS: This work suggests that certain brain regions may be more sensitive to CRT and CMB formation, although the down stream effects on brain structure and function may be more global, and is currently being validated in a larger cohort.