tbuckley/cabot-search huggingface dataset:
Study KBP-2010-CPHG: Characteristics and management of 968 new cases of small-cell lung cancer (SCLC).
Authors: Charles Dayen, Daniel Coëtmeur, Celine Lecerf, Adrien Diximier, Bertrand Lemaire, Michel Martin, Marie-Pierre Lafourcade, Gislaine Fraboulet, Guillaume Leveiller, Emmanuelle Lecuyer, Jean-Pierre Mathieu, Cecilia Nocent-Ejnaini, Patrick Dumont, Marc Peureux, Stephanie Dehette, Chrystele Locher, Jacques Le Treut, Didier Debieuvre, Francis Martin, Michel Grivaux
Journal: Journal of Clinical Oncology (2013)

e19078 Background: In recent years, many major advances have been made in non-small-cell lung cancer (NSCLC), and in particular in adenocarcinoma, but not in SCLC. In 2010, the French College of General Hospital Respiratory Physicians (CPHG) performed a prospective multicentre epidemiological study (KBP-2010-CPHG) to describe the baseline characteristics and management of all new cases of primary lung cancer and to evaluate survival. The present abstract reports results in SCLC patients. Methods: 7,051 patients ≥18 years presenting with a new case of primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010 and managed in the respiratory department of one of the 104 general hospitals participating in the study, were included. A standardised form was completed for each patient. A steering committee checked data collection exhaustiveness. SCLC data were analysed separately. Results: There were 968 SCLC patients: mean age, 65.6 years (+/-10.6); 23.2% female; 4.4% non-smokers (11 % in women), 35.8% ex-smokers, 59.8% current smokers; 63.4% with performance status 0 or 1; 59.9% having lost weight within the previous 3 months (19.8% of whom had lost &gt;10 kg). Main tumour characteristics at diagnosis were: 71.2% stage IV, 24.7% stage IIIA or IIIB, 4.1% of stage &lt;III. 15.2% of patients received chemo-radiotherapy and 73.4% chemotherapy (86.2% platinum-based). Carboplatin was more commonly used in patients &gt;70 (59.1%) than &lt;70 years of age (40.9 %). One-year mortality was 64.2%. Compared with NSCLC patients, patients with SCLC more frequently were active smokers (59.8% vs.47.6%), lost weight (59.9% vs. 52.4%), and presented with stage IV tumour at diagnosis (71.2% vs. 58.3%); first line therapy was more frequently platinum-based chemotherapy (86.2% vs. 61.2%) and less frequently curative surgery (1.6% vs. 19%), and mortality was higher (64.2% vs. 55.2%). Conclusions: In 2010, prognosis remains poor in SCLC. Compared with NSCLC, it was more frequently associated with active smoking and stage IV disease, and showed a lower rate of surgery.
P14.68 Life expectancy in biopsied GBM patients: a single-centre experience
Authors: O Kalita, Z Sporikova, M Halaj, K Cwiertka, M Vaverka, L Hrabalek, R Trojanec, M Hajduch, J Drabek, J Vrbkova
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The prognosis for patients with GBM remains dismal. The most aggressive multimodal therapy (maximally radical and safe tumour resection, followed by the Stupp protocol oncotherapy) has yielded the best treatment outcomes. Only a small proportion of patients initially undergo brain tumour biopsy. Our aim is to evaluate therapy results of biopsied GBM patients. MATERIAL AND METHODS We followed all glioma patients from June 1, 2006. Information on surgeries, patient clinical condition, imagings, and results of histological, immunohistochemical, molecular genetic, and cytogenetic investigations was gathered. For this study, we selected a group of biopsied GBM patients in a period from June 1, 2006 to December 31, 2016. Needle biopsy (stereotactic, or navigated) was advised for unresectable tumours, for patients with unfavourable clinical conditions (KS&lt;60), and for older patients (with age being the only surrogate criterion). Whenever possible, the patients were recommended Stupp protocol oncotherapy. Clinical and MRI follow-up after surgery was carried out (OS, PFS) until the patient’s demise. RESULTS Sixty adult GBM patients (27 females and 33 males) with their age ranging from 30 to 85 years old and with a mean age of 66.8 years were enrolled in this study. The diagnosis of GBM was established by biopsy. Fourteen of them (23%) had radiotherapy only. Five patients (8%) were able to receive the Stupp protocol oncotherapy. Forty-one patients (69%) had an unfavourable physical condition which was a contraindication to radiotherapy or chemotherapy, respectively. The average OS was 3.8 months. A limited number of samples were available for IDH status investigation. All of the seventeen GBMs were IDH wild-type. CONCLUSION The initial surgical treatment strategy in GBM patients must be in the hands of an experienced neurosurgeon. Biopsy is required even when no further tumour-specific therapy is recommended. Regardless of the treatment strategy (resection or biopsy), multisite tumour sampling should be acquired. In our opinion, a decision to perform needle biopsy should be restricted to patients with unfavourable clinical conditions (age, KS, comorbidities, etc.), to large and deep-located brain tumours very often involving midline structures (corpus callosum, thalamus, basal ganglia), and to older patients. In accordance with these principles, we selected a small GBM patient group (12% of all GBM patients) with very limited life expectancy. The rationale for brain tumour biopsy is prevention of histological misdiagnosis and collection of biomarker data. But only the limited size of the tissue samples obtained was a significant obstacle to comprehensive cytogenetic investigation. We also recommend not to include biopsied GBM patients in studies with patients who had a radical resection. Supported by Ministry of Health of the Czech Republic, grant nr. NV19-04-00281.
Doctor clashes with Rees-Mogg over risks of no deal Brexit
Authors: Gareth Iacobucci
Journal: BMJ (2019)

A consultant neurologist who helped draw up the government’s contingency plans for exiting the European Union without a deal has clashed with the leader of the House of Commons, Jacob Rees-Mogg, over the potential risks to patients from a no deal Brexit.

David Nicholl, who was involved in developing the mitigation plans for the government’s Operation Yellowhammer in March, called in to LBC’s Nick Ferrari radio show to ask Rees-Mogg what mortality he was willing to accept if a no deal Brexit occurred. Nicholl said that lives were at risk from potential shortages of drugs …
OS4.2 Phase 0 trial of Ceritinib in brain metastasis and recurrent glioblastoma
Authors: R Fiorelli, J Li, X Bao, A DeRogatis, C Pennington-Krygier, S Kim, S Mehta, N Sanai
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ceritinib is an orally bioavailable, small molecule inhibitor for ALK/IGFR1/FAK, which are highly expressed in glioblastoma and brain metastases. Preclinical and clinical data suggest that ceritinib has activity in central nervous system (CNS) malignancies, but to date there is no direct evidence in patients. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in recurrent glioblastoma and brain metastasis patients. MATERIALS AND METHODS Three brain metastasis and seven glioblastoma patients with high expression of pSTAT5b/pFAK/pIGFR1 were enrolled and treated with oral ceritinib daily (750 mg) for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at ~ 4 and 24 h following the last dose. Total and unbound drug concentrations were determined using LC-MS/MS. PD response was assessed by immunohistochemical analysis of pALK, pFAK, pIGFR1, and pIRS1 staining in treated tumor and matched archival tissues. RESULTS Ceritinib was highly bound to human plasma protein (median fraction unbound (Fu), 1.4%) and to brain tumor tissue (median Fu, 0.073% and 0.14% in enhancing and non-enhancing regions respectively). There was a large interindividual variability in drug CNS penetration, with the median unbound concentrations in enhancing, non-enhancing, and CSF of 0.040, 0.006, and 0.012 µM, respectively. The median unbound tumor-to-plasma ratio was 2.44 and 0.33 in enhancing and non-enhancing areas, respectively. In one patient with brain metastasis, drug binding to enhancing tumor was significantly lower (Fu, 1.62%), resulting in a higher unbound drug tumor concentration and CSF concentration as compared to those in glioblastoma patients. In all patients, no changes in PD markers were detected. CONCLUSION Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastasis and glioblastoma are unlikely sufficient for target modulation.
Pulmonary Lipid-Laden Macrophages and Vaping
Authors: Sean D Maddock, Meghan M Cirulis, Sean J Callahan, Lynn M Keenan, Cheryl S Pirozzi, Sanjeev M Raman, Scott K Aberegg
Journal: New England Journal of Medicine (2019)

Pulmonary Lipid-Laden Macrophages and Vaping The use of electronic cigarettes has been associated with pulmonary injury, one feature of which has been lipid-laden macrophages in pulmonary-lavage fl...
Abstract 12261: Reduced Subclinical and Clinical Atherosclerosis by a Treat-to-Target Intervention of Cardiovascular Risk Factors in Rheumatoid Arthritis: Results of the francis, a Randomized Clinical Trial
Authors: Benjamin Burggraaf, Deborah F van Breukelen van der Stoep, Marijke A de Vries, Boudewijn Klop, Anho H Liem, Gert-Jan M van de Geijn, Noelle van der Meulen, Erwin Birnie, Ellen van der Zwan, Jende van Zeben, Manuel Castro Cabezas
Journal: Circulation (2018)

Introduction: Patients with Rheumatoid Arthritis (RA) have an increased risk for cardiovascular disease (CVD) compared to the general population. No long term intervention trials on CVD risk factor...
SAT0705-HPR PATIENTS’ EXPERIENCES OF REASONS TO BEING PHYSICALLY ACTIVE IN EARLY RHEUMATOID ARTHRITIS – A MIXED METHODS STUDY
Authors: Maria Qvarfordt, Maria Andersson, Ingrid Larsson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The importance of physical activity in rheumatoid arthritis (RA) is well known and patients are informed about the importance of being physically active. Despite this knowledge there is a lack of compliance to this advice. Studies comparing physical activity in different groups of patients with RA and reasons influencing physical activity are needed. <h3>Objectives</h3> The objectives were to compare physical activity (PA) in workers, retired and patients with sick-leave with early RA and further to explore reasons to being physically active in these patients. <h3>Methods</h3> A total of 66 patients with early RA were included in the study. A sequential explanatory mixed methods design was used. The groups were compared with clinical data as: disease activity (DAS28); pain (VAS 0-100, best to worst); health-related quality of life (EQ5D, -0.594-1 worse to best) and a physical function (HAQ, 0-3 best to worst). ESR and CRP. Patients were dichotomized as being active on recommended levels of PA (MVPArec; physically active on a moderate level ≥150min/week (MPA) or on an intense level ≥75min/week (VPA)) or not (sedentary). The patients were grouped on self-reported working ability; workers, patients with sick-leave and retired patients. Qualitative data was collected by a questionnaire with open-ended questions about reasons influencing PA. The qualitative data was analysed with a manifest qualitative content analysis to gain a greater understanding of patients' experiences of PA in early RA. <h3>Results</h3> There were no significant differences between the groups in disease activity, physical function, swollen joints, health-related quality of life or inflammatory parameters (ESR, CRP). Patients on sick-leave had more tender joints median (min-max) 9 (2-18) vs. 4 (0-20) and 3 (0-10), p=0.013. Workers reported higher intensity of pain, though not significant. Retired patients fulfilled MVPA criteria to a higher rate (86%) than workers (42%) or patients with sick-leave (40%), p=0.010. The qualitative content analysis resulted in three categories. Reasons to being physically active in patients with early RA were; limitations (pain, physical function, stiffness, limited strength and fatigue), awareness as motivation (fear of movement and health benefits) and external environment (weather, transports to activity, economy and time, especially for workers). <h3>Conclusion</h3> Knowledge of reasons to being physically active in patients with RA is important to facilitate and support the patients. Joint pain seems to be an issue for patients with sick-leave. This could be associated to fear of movement and in this aspect these patients need to be supported. Time could be a limiting issue for working patients, which need to be highlighted and solved for these patients. <h3>Disclosure of Interests</h3> None declared
成人 AD 中的心理健康
Authors: J.I. Silverberg, J.M. Gelfand, D.J. Margolis, M. Boguniewicz, L. Fonacier, M.H. Grayson, P.Y. Ong, Z.C. Chiesa Fuxench, E.L. Simpson
Journal: British Journal of Dermatology (2019)

特应性皮炎(AD)也简称为湿疹,是一种导致瘙痒性皮疹的长期皮肤病。搔抓可导致皮肤渗液,结痂,感染和增厚。美国有 1650 万人患有特应性皮炎,660 万人报告中重度症状。发现病情越严重,生活质量越差,抑郁和焦虑的风险越高。 这项基于美国的研究调查了 2,893 名成人,以了解患有特应性皮炎和其严重程度是否影响同时存在焦虑或抑郁的可能性。通过发送一份调查收集了信息。使用改良英国诊断标准筛查特应性皮炎患者。由患者使用例如患者来源湿疹测量和皮肤病学生活质量指数等工具来自行报告疾病严重程度。使用医院焦虑和抑郁量表 (HADS) 测量焦虑和抑郁。 602 名成人患有特应性皮炎。他们的 HADS 评分高于(意味着焦虑和抑郁水平更高) 2291 名无特应性皮炎的成人。在特应性皮炎成人中,同时有焦虑或抑郁正式诊断的人数多于在无特应性皮炎的成人中。但是,很多 HADS 评分高的特应性皮炎患者并没有焦虑或抑郁的正式诊断。此外,特应性皮炎较严重患者的 HADS 评分较病情较轻患者更高。 结论是,特应性皮炎增加焦虑和抑郁的可能性,尤其当病情严重时。这可能被漏诊。
Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection
Authors: Alexandre Grassart, Valérie Malardé, Samy Gobaa, Anna Sartori-Rupp, Jordan Kerns, Katia Karalis, Benoit Marteyn, Philippe Sansonetti, Nathalie Sauvonnet
Journal: Cell Host & Microbe (2019)
P14.19 The inverse paradigm of IDH-wildtype glioblastoma is fundamental to overcome the two causes of resistance and develop novel effective therapies
Authors: E Brognaro
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND IDH-wildtype glioblastoma behaves differently from all other solid tumors. This is the reason why after decades of praiseworthy therapeutic efforts, the prognosis remains very poor. Many clues (radiological, clinical, surgical) and recent indirect experimental evidence converge to indicate that the entire brain parenchyma is micro-infiltrated from the very beginning by the founding clone before the primary bulk has started its growth. Therefore, only in IDH-wildtype glioblastoma the malignant (i.e. distantly infiltrating the organ of origin) and deadly (leading cause to patient’s death) phases coincide and overlap in one single phase. MATERIALS AND METHODS Appropriate sampling procedures must absolutely take into consideration both the tumor bulk and the micro-infiltrated brain parenchyma. They can be performed (with full respect for ethical issues) analyzing neoplastic and “healthy” material obtained from living patients (a), using animal models (b), studying post-mortem samples from rapid autopsies (c), comparing local and distant recurrences with the primary bulk (d). The study and analysis of the bulk tumor must be carried out by collecting multiple multiregional spatially separated samples throughout the whole tumor mass. The analysis of the micro-infiltrated brain parenchyma in living patients can be performed appropriately and ethically also from surgical patient tissue. RESULTS The phylogenetic tree of the tumor bulk must be inferred and reconstructed by the collection and analysis of multiple regionally separated samples. Additionally, driver and passenger events will be identified as well as the CSCs of samples. The procedures to ethically sample the micro-infiltrated brain parenchyma enable us to collect and identify the founder CSCs which lie quiescent in the perivascular parenchymal niches across the whole brain. Indeed, distant recurrences are due to their activation. CONCLUSION IDH-wildtype glioblastoma is the only brain tumor which arises from astrocyte-like cells of the SVZ ribbon layer and it is able to micro-infiltrate the whole supratentorial brain parenchyma before starting its growth. Its unique inverse paradigm explains the emergence of distant recurrences (sharing only truncal mutations with the primary bulk) and adds, in addition to the heterogeneity of the primary bulk and its residues, a second crucial cause of resistance to take into account (i.e. the founder CSCs which reside quiescent, in G0 state, in the perivascular parenchymal niches). Therefore, innovative therapies must identify and selectively target either CSCs unique properties related to their impaired asymmetrical division or stable driver lesions of the founder CSC (without alternative mutations and pathways) or exclusive markers used by the founder CSCs to settle dormant (involving mechanisms of adhesion, anchorage and cell cycle arrest) in their niches.
Impact of Public Health Interventions on Drinking Water–Associated Outbreaks of Hepatitis A — United States, 1971–2017
Authors: Catherine E. Barrett, Bryn J. Pape, Katharine M. Benedict, Monique A. Foster, Virginia A. Roberts, Kenneth Rotert, Mia C. Mattioli, Jonathan S. Yoder
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Hepatitis A virus (HAV) is an RNA virus primarily transmitted via the fecal-oral route and, in rare cases, causes liver failure and death in infected persons. Although drinking water-associated hepatitis A outbreaks in the United States are rarely reported (1), HAV was the most commonly reported etiology for outbreaks associated with untreated ground water during 1971-2008 (2), and HAV can remain infectious in water for months (3). This report analyzes drinking water-associated hepatitis A outbreaks reported to the Waterborne Disease and Outbreak Surveillance System (WBDOSS) during 1971-2017. During that period, 32 outbreaks resulting in 857 cases were reported, all before 2010. Untreated ground water was associated with 23 (72%) outbreaks, resulting in 585 (68.3%) reported cases. Reported outbreaks significantly decreased after introduction of Advisory Committee on Immunization Practices (ACIP) hepatitis A vaccination recommendations* and U.S. Environmental Protection Agency's (USEPA) public ground water system regulations.† Individual water systems, which are not required to meet national drinking water standards,§ were the only contaminated drinking water systems to cause the last four reported hepatitis A outbreaks during 1995-2009. No waterborne outbreaks were reported during 2009-2017. Water testing and treatment are important considerations to protect persons who use these unregulated systems from HAV infection.
P11.48 Dose-dependent effects of radiation exposure on the cell culture of glioblastoma G01, obtained from the patient with a long-term survival
Authors: A Belyashova, A Golanov, G Pavlova, E Savchenko, N Antipina, D Panteleev, D Shamadykova, G Smirnov, A Nikolaeva
Journal: Neuro-Oncology (2019)

Abstract Background: The predictors of a favorable prognosis regarding radiation exposure in patients with glioblastoma have not been studied enough, therefore, the search for factors determining a tumor response to the combined chemoradiation treatment is an actual task at present. DNA repair protein RAD51 homolog 1 (RAD51) is a crucial protein for homologous recombination and its inhibition has been shown to sensitize glioma stem cells to irradiation. Materials and Methods: G01 primary glioblastoma cell culture was obtained from tumor tissues from patient with long term survival (42 month).An irradiation with the energy of 6 MeV was carried out in 1 fraction 20,40,60,80,100,125,150,200,250 Gy with Linac. mRNA expression of the RAD51 gene, XRCC6, XRCC5 genes, relative amount of RAD51 protein and Ku70, Ku80 proteins, proliferative activity of cell culture was evaluated by RT-PCR, Western blotting, MTT-test, respectively.Results: When G01 cells were irradiated with doses from 5 to 180 Gy there was a uniform linear decrease in the population of proliferating cells compared to the control, but at a dose of 200 Gy a rise to 24% was observed. The mRNA expression of the RAD51 gene increased 2 times after irradiation at a dose of 20 Gy compared with control and then increased, reaching a peak at the level of 100,250 Gy. Minimal expression was observed after irradiation at a dose of 20 and also decreased at 200 Gy. The mRNA expression of the XRCC5 gene increased 2-fold after irradiation at a dose of 20 Gy compared with control and then decreased, remaining at the same level. Minimal expression was observed after irradiation at a dose of 200Gy. The relative amount of Ku80 protein reached a peak at a dose of 100 Gy, followed by a decrease. Maximum expression level of mRNA of the XRCC6 gene was observed after irradiation at a dose of 250Gy. The relative amount of Ku70 protein also decreased at 200 Gy and reached a peak at a dose of 250 Gy. Conclusions: After irradiation transplantable G01 cell culture from patient with long term survival a linear decrease in proliferative activity depending on the dose was observed with an decrease in mRNA expression of Rad51 gene and the relative amount of RAD51,Ku70 in dose level of 200Gy that could potentially indicate sensitivity point to radiation exposure in these cell culture. Further studies using cell cultures from patients may help in understanding the mechanisms of radioresistance and radiosensitivity in glioblastoma.The research was supported financially by RFBR (Project No. 18-29-01061).
OS9.2 Radiomics analysis of lower-grade gliomas, a POLA Network study
Authors: N Younan, H Douzane, A Duran-Pena, L Nichelli, Y Garcilazo, C Dehais, F Ducray, C Carpentier, K Mokhtari, D Figarella-Branger, J Delattre, A Idbaih, A Alentorn
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Lower-grade gliomas (LGG) are divided into three histo-molecular groups: i) IDH-wildtype, ii) IDH mutant and 1p19q intact and iii) IDH mutant and 1p19q co-deleted. The current classification has improved the clinical stratification and its reproducibility. However, LGGs are still associated with an important degree of clinical heterogeneity. We sought to analyze the cross-talk between the spatial distribution and the quantitative imaging features (radiomics) with the clinical evolution and their molecular background (radiogenomics). MATERIAL AND METHODS We performed a retrospective multicentric study from 4 cohorts of high-grades gliomas (POLA Network, TCGA, REMBRANDT and LGG-1p19q), totaling 900 gliomas. We performed N4 and WhiteStripe imaging corrections to standardize MRI intensities. We used ITK-SNAP to obtain a mask of the different habitats of the tumor. Then we used PyRadiomics to obtain 2616 radiomic features per sample. We used plsRcox for fitting several Cox model in high-dimensional settings. We assessed the performance of the difference Cox model with the Harrel’s concordance index. We used a Sparse Canonical Correlation analysis to analyze the spatial distribution of the tumors. RESULTS Radiomics features allow identification in an unsupervised manner IDH-mutant gliomas with a median AUC of 0.96 [0.92–0.98]. Interestingly, in the analysis of survival, radiomics features provided additional information to clinical or genetics covariates and the model with only radiomics features obtained a C-Index of 0.78 [0.72–0.82]. In addition, survival model with the best performance in the prediction of overall survival was the one combining radiomics, clinics and genetics features with a C-Index 0.85 [0.82–0.92] and was validated in the other cohorts. The analysis of spatial distribution showed a very strong distribution of 1p19q co-deleted oligodendrogliomas in the frontal lobes. CONCLUSION Radiomics features may provide additional relevant clinical information by improving the prognosis of LGG. Radiomics allow non-invasive prediction of the most relevant molecular alterations of LGG.