tbuckley/cabot-search huggingface dataset:
Three steps to changing the narrative about knee osteoarthritis care: a call to action
Authors: JP Caneiro, Peter B O'Sullivan, Ewa M Roos, Anne J Smith, Peter Choong, Michelle Dowsey, David J Hunter, Joanne Kemp, Jorge Rodriguez, Stefan Lohmander, Samantha Bunzli, Christian J Barton
Journal: British Journal of Sports Medicine (2019)

Knee osteoarthritis (OA), characterised by knee pain and functional limitation,1 2 is widely understood to imply that symptoms are due to structural damage. This view leads to the belief that non-surgical approaches are futile and the structural damage needs to be ‘fixed’.3 4 In contrast, contemporary evidence supports knee OA as a ‘whole person condition’ in which knee health is influenced by the interaction of different biopsychosocial factors that modulate inflammatory processes and tissue sensitivity, as well as behavioural responses that lead to pain and disability.5 6 This contrasting view reinforces the critical role of non-surgical approaches to manage knee OA. To promote this conceptual shift in understanding knee OA, clinicians must take three key actions.

Clinicians must explain that knee pain is a modifiable symptom related to sensitised knee structures and influenced by a variety of biopsychosocial factors, rather than solely related to damaged structures. This message is underpinned by knowledge that levels of pain and disability are often poorly explained by the degree of structural change on imaging; and that symptoms are influenced by a person’s individual context, including life stage, psychological, social, physical and lifestyle factors, and health comorbidities. Clinicians should deliver this message with a focus on the person’s own narrative and …
P08.06 Clinical value scores for treatment of newly diagnosed glioblastoma with TTFields
Authors: J Kelly, C Proescholdt
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND High quality and value of recommended treatments is of specific importance in cancer care. ESMO, ASCO and NCCN have developed tools intended to help assessing the clinical value of cancer treatments in a standardised way, allowing for a comparative discussion. Tumor treating fields (TTFields) is a novel, device based cancer treatment, that was recently demonstrated to be effective in newly diagnosed glioblastoma (GBM). This new modality augments the treatments discussed with glioblastoma patients today. MATERIAL AND METHODS ESMO and ASCO frameworks each calculate a score for the clinical value of a cancer treatment, called Magnitude of Clinical Benefit Scale (MCBS) by ESMO and the Net Health Benefit (NHB) by ASCO. NCCN self reports “evidence blocks” which are assessed by clinician panels and were recently published for the first line treatment of newly diagnosed GBM with TTFields. We apply and compare the ESMO, ASCO and NCCN tools for TTFields treatment of newly diagnosed GBM. RESULTS The resulting ASCO NHB score for TTFields treatment of newly diagnosed GBM is 56. ESMO MCBS scores for TTFields in GBM are resulting in A/5, these being the highest achievable scores for this framework. All frameworks value the increase in overall survival by TTFields and the moderate toxicity profile. ESMO additionally values quality of life, while ASCO values palliation and treatment free intervals. NCCN’s specific focus is on the quality and consistency of the evidence. NCCN evidence blocks also contain an affordability score. CONCLUSION All three frameworks consider the clinical efficacy of a treatment and it’s toxicity profile in their clinical value assessment. Beyond that, their respective focus is on slightly different aspects and their definition of clinical value therefore varies in detail. However, all value scores suggest that TTFields treatment of newly diagnosed GBM provides a substantial clinical benefit. The high ESMO and ASCO scores are based on the significantly extended progression free and overall survival for TTFields treated patients, without adding systemic toxicities. The NCCN evidence blocks strongly support the NCCN category 1 recommendation for the use of TTFields in newly diagnosed GBM.
Health-related quality of life of newly diagnosed chronic myeloid leukemia patients treated with first-line dasatinib versus imatinib therapy
Authors: Fabio Efficace, Fabio Stagno, Alessandra Iurlo, Massimo Breccia, Francesco Cottone, Massimiliano Bonifacio, Elisabetta Abruzzese, Fausto Castagnetti, Giovanni Caocci, Monica Crugnola, Isabella Capodanno, Bruno Martino, Mario Tiribelli, Andrea Patriarca, Antonella Gozzini, Patrizia Pregno, Susanne Saussele, Nicola Cascavilla, Claudio Fozza, Micaela Bergamaschi, Gianni Binotto, Marco Vignetti, Gianantonio Rosti
Journal: Leukemia (2019)
Getting Back to Nature: Feralization in Animals and Plants
Authors: Eben Gering, Darren Incorvaia, Rie Henriksen, Jeffrey Conner, Thomas Getty, Dominic Wright
Journal: Trends in Ecology & Evolution (2019)

HighlightsFeral animals and plants have become ubiquitous worldwide, but their evolution has not been well studied.The process of feralization offers unique and important opportunities to study adaptive evolution, often in model systems inhabiting diverse, novel, and/or changing environments.Recent work shows that feral taxa undergo rapid evolutionary changes at loci controlling an array of fitness-related traits, including morphology, behavior, and development.Gene flow between domesticated and wild populations has important, diverse, and context-dependent effects on fitness in recipient populations.Legacies of domestication are seen in many feral plants and animals. These features can have important and unexpected roles in subsequent adaptation to changing (e.g., feral) environments.AbstractFormerly domesticated organisms and artificially selected genes often escape controlled cultivation, but their subsequent evolution is not well studied. In this review, we examine plant and animal feralization through an evolutionary lens, including how natural selection, artificial selection, and gene flow shape feral genomes, traits, and fitness. Available evidence shows that feralization is not a mere reversal of domestication. Instead, it is shaped by the varied and complex histories of feral populations, and by novel selection pressures. To stimulate further insight we outline several future directions. These include testing how 'domestication genes' act in wild settings, studying the brains and behaviors of feral animals, and comparative analyses of feral populations and taxa. This work offers feasible and exciting research opportunities with both theoretical and practical applications.
Inclusion of Clinical Trial Registration Numbers in Conference Abstracts and Conformance of Abstracts to CONSORT Guidelines
Authors: Elizabeth C. Wright, Devika Kapuria, Gil Ben-Yakov, Disha Sharma, Dev Basu, Min Ho Cho, Kenneth J. Wilkins
Journal: JAMA Internal Medicine (2019)

This cross-sectional study reviews abstracts presented at 8 major medical and surgical conferences held in 2017 to assess the extent to which abstracts reporting randomized clinical trial results cite trial registration numbers and conform to key CONSORT guidelines.
P05.08 High-grade gliomas and immunotherapeutic early phase clinical trials: a single-center experience
Authors: M Simonelli, P Persico, A Dipasquale, E Lorenzi, L Giordano, F Pessina, P Navarria, M Scorsetti, L Bello, A Santoro
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with high-grade gliomas (HGGs) have historically been excluded from immunotherapeutic early-phase clinical trials (ieCTs) due to unavailability of serial bioptic sampling, the frequent need of corticosteroids, concerns regarding activity of immunotherapy in central nervous system, and rapid clinical deterioration. MATERIAL AND METHODS We retrospectively reviewed data of all recurrent HGG patients enrolled in ieCTs at Humanitas Cancer Center Phase I Unit between 2014 and 2019. Disease control rate (DCR) according to RANO criteria, six-months progression-free and overall survival (PFS-6; OS-6), and treatment-related adverse events (TRAEs), were evaluated. A control-cohort (CC) of patients treated with standard treatments (temozolomide, fotemustine, lomustine and procarbazine, bevacizumab) matched (1:1) for sex, age, line of treatment, MGMT methylation status, and IDH mutational status, was selected for comparison. A series of clinical parameters with an established prognostic value for patients with solid tumors treated into ieCTs were correlated with survivals through an univariate analysis. These include: use of steroids, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, lactate dehydrogenase, albumin, total protein. RESULTS Five among the 23 ieCTs conducted at our Phase I Unit allowed inclusion of HGG patients. 25 patients were enrolled in the experimental cohort (EC): 22 (88%) glioblastoma, 3 (12%) anaplastic astrocytoma. Median age was 50 years (range 25–71); 16 patients (64%) were men, 9 (36%) women; 17 pts (68%) required steroid therapy, with a median baseline dexamethasone dose of 2 mg (range 1–6). The median number of prior systemic therapies was 1 (range 1–2). Twelve patients (48%) received monotherapies (anti PD-1, anti CSFR-1, anti TGF-ß, anti cereblon), 13 (52%) combination regimens (anti PD-L1 + anti CD38, anti PD-1 + anti CSFR-1). DCR was 40% (1 CR + 2 PR + 7 SD) and 37% (9 SD), in EC and CC, respectively. Four patients (16%) in EC had grade ≥3 TRAEs (1 neutropenia, 1 pneumonia, 2 hepatitis). With a median follow-up of 14 months PFS-6 were 35% and 16% (p=0.075), in EC and CC respectively, while OS-6 was significantly improved in the EC (82% vs 44%, p=0.004). In our small series, none of clinical factors resulted prognostic. CONCLUSION Survival outcomes of ourHGG patients treated into ieCTs compared very favorably with a matched CC. Inclusion of HGGs patients into ieCTs should be strongly encouraged. Identification of clinical factors to select who may benefit from ieCTs still remains crucial.
CYFRA 21‐1 and CEA combination assay in EMPD
Authors: Y. Nakamura, K. Tanese, I. Hirai, M. Amagai, Y. Kawakami, T. Funakoshi
Journal: British Journal of Dermatology (2019)

Extramammary Paget's disease (EMPD) is a rare skin cancer affecting the genitals and armpit regions. EMPDs occur mainly in Caucasian women and Asian men over the age of 60, in less than 0.6 per 100,000 people. Basic treatment is excision (removal) by operation, yet metastasis, meaning that it has spread, is seen in around 10% of patients. If the cancer is spreading, it is really important to detect this and start treatment as early as possible, since in late stages the disease can be hard to treat. A biomarker, or marker, is a molecule found in blood, different levels of which correspond with how well the body responds to a treatment, or to how the disease will progress. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) are both biomarkers for certain other cancers, and it has been suggested that they might also be markers for monitoring tumour progression in EMPD; however, neither the accuracy of, nor correlation between, these markers have been examined in EMPD patients. This study from Japan aimed to find out the usefulness and relationship of CEA and CYFRA21-1 levels in blood of EMPD patients in various progression states of the disease. A total of 30 EMPD cases were included in this study. In all early-stage patients, CEA and CYFRA were within normal levels. In advanced-stage patients, CEA and CYFRA were elevated in 79% and 63%, respectively. Either CEA or CYFRA was found to be elevated in 95% of the advanced patients, indicating that a certain number of patients have raised levels of only one of the markers. In addition, both of the markers also correlated well with the treatment responses in all patients. This study revealed that examining both CEA and CYFRA may help to detect advanced-stage EMPD patients, and that they are useful for monitoring treatment responses.
Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity
Authors: Jiong Hu, Sofia-Iris Bibli, Janina Wittig, Sven Zukunft, Jihong Lin, Hans-Peter Hammes, Rüdiger Popp, Ingrid Fleming
Journal: Journal of Clinical Investigation (2019)

Polyunsaturated fatty acids such as docosahexaenoic acid (DHA) positively affect the outcome of retinopathy of prematurity (ROP). Given that DHA metabolism by cytochrome P450 and soluble epoxide hydrolase (sEH) enzymes affects retinal angiogenesis and vascular stability, we investigated the role of sEH in a mouse model of ROP. In WT mice, hyperoxia elicited tyrosine nitration and inhibition of sEH and decreased generation of the DHA-derived diol 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP). Correspondingly, in a murine model of ROP, sEH-/- mice developed a larger central avascular zone and peripheral pathological vascular tuft formation than did their WT littermates. Astrocytes were the cells most affected by sEH deletion, and hyperoxia increased astrocyte apoptosis. In rescue experiments, 19,20-DHDP prevented astrocyte loss by targeting the mitochondrial membrane to prevent the hyperoxia-induced dissociation of presenilin-1 and presenilin-1-associated protein to attenuate poly ADP-ribose polymerase activation and mitochondrial DNA damage. Therapeutic intravitreal administration of 19,20-DHDP not only suppressed astrocyte loss, but also reduced pathological vascular tuft formation in sEH-/- mice. Our data indicate that sEH activity is required for mitochondrial integrity and retinal astrocyte survival in ROP. Moreover, 19,20-DHDP may be more effective than DHA as a nutritional supplement for preventing retinopathy in preterm infants.
Underdetection of laboratory-confirmed influenza-associated hospital admissions among infants: a multicentre, prospective study
Authors: Mark G Thompson, Min Z Levine, Silvia Bino, Danielle R Hunt, Tareq M Al-Sanouri, Eric A F Simões, Rachael M Porter, Holly M Biggs, Lionel Gresh, Artan Simaku, Illham Abu Khader, Veronica L Tallo, Jennifer K Meece, Meredith McMorrow, Edelwisa S Mercado, Sneha Joshi, Nicholas P DeGroote, Iris Hatibi, Felix Sanchez, Marilla G Lucero, Samir Faouri, Stacie N Jefferson, Numila Maliqari, Angel Balmaseda, Diozele Sanvictores, Crystal Holiday, Cristina Sciuto, Zachary Owens, Eduardo Azziz-Baumgartner, Aubree Gordon
Journal: The Lancet Child & Adolescent Health (2019)
SCLE 和皮肌炎与抗 PD‐1 治疗
Authors: A.L. Marano, J.M. Clarke, M.A. Morse, A. Shah, W. Barrow, M.A. Selim, R.P. Hall, A.R. Cardones
Journal: British Journal of Dermatology (2019)

PD-1抑制剂是一种相对新型的药物, 用于治疗转移性 (播散性) 癌症患者。其示例包括称为帕博利珠单抗和纳武利尤单抗的药物。不幸的是, 这类治疗可能与自身免疫副作用相关, 后者意味着身体防止感染的免疫系统错误地攻击身体的某些部位。与PD-1抑制剂相关的自身免疫副作用的示例包括结肠炎、甲状腺疾病和皮肤炎症(包括湿疹样皮疹和白癜风)。这项研究的作者来自美国杜克大学, 他们描述了两名在PD-1 治疗期间发生了一型称为皮下型皮肤红斑狼疮 (SCLE) 的狼疮的患者。SCLE 是一种自身免疫性疾病。在一份病例中, 正在使用的药物纳武利尤单抗被停用; 肿瘤科医生们未能通过英夫利昔单抗 (一种称为 TNFα 抑制剂的药物) 成功治疗该患者, 但皮肤科医生通过药膏和羟氯喹治疗控制了皮疹。由于纳武利尤单抗正在帮助治疗这名患者的癌症, 此药物被重新启用, 但不幸的是, 他之后出现了另一种自身免疫性疾病皮肌炎的特征, 因此该药物被停用。第二名患者在帕博利珠单抗治疗后发生了 SCLE,由于这一治疗对她的癌症没有作用故被停用。她的 SCLE 通过治疗也得到了控制。作者们发现,TNF 抑制剂治疗在这种情况下效果并不理想, 因为它本身就可能导致狼疮。尽管已确认 SCLE 是很多药物的副作用, 一种药物导致两种不同的结缔组织病 (狼疮和皮肌炎) 是不常见的。作者们建议在此情况下不要继续使用此药物。
In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury
Authors: Nikos Gorgoraptis, Lucia M. Li, Alex Whittington, Karl A. Zimmerman, Linda M. Maclean, Claire McLeod, Ewan Ross, Amanda Heslegrave, Henrik Zetterberg, Jan Passchier, Paul M. Matthews, Roger N. Gunn, Tom M. McMillan, David J. Sharp
Journal: Science Translational Medicine (2019)

Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1-42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.
P12.06 Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas
Authors: A Sharma
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Immune check-point blockade targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in the treatment of advanced cancer. The prognosis of the ‘ST-RELA’ and ‘PF-A’ molecular subgroups of ependymomas (EPN) remains poor. This study aims to understand the potential candidature of EPNs for ICB. MATERIAL AND METHODS All supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP and ST-not otherwise specified (NOS), based on L1CAM protein expression and/or presence of RELA/YAP1 fusion transcripts by RT-PCR. All posterior fossa (PF) BEPNs were classified into PF-A and PF-B based on H3K27me3 protein expression and chromosome 1q gain. Immunohistochemistry for PD-L1 (SP263, Ventana) and CD8 was performed. RelA protein enrichment at PDL1 promoter site was analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. RESULTS A total of 83 intracranial EPNs were included as follows: ST-RELA (n=32), ST-YAP (n=1), ST-NOS (n=11), ST-subependymoma (n=1), PF-A (n=25) and PF-B (n=13). Median tumor infiltrating CD8+ cytotoxic T-lymphocyte (CTL) density was 6/mm2, and was higher in ST EPNs (median 10/mm2) as compared to PF EPNs (median 3/mm2). PD-L1 protein expression in ≥1% tumor cells was noted in 17/83 (20%) of all EPNs, including 12/32 (37%) of ST-RELA and rare ST-NOS (2/11), PF-A (2/25) and PF-B (1/13) tumors. Twelve intracranial EPNs (14%, 12/83) showed high CTL density and concurrent PD-L1 positivity, of which majority (83%, 10/12) were ST-RELA EPNs. Enrichment of RelA protein was seen at PD-L1 promoter. CONCLUSION Increased CTL densities and upregulation of PD-L1 in ST-RELA ependymomas suggests potential candidature for immunotherapy.
OS9.4 The added value of radiomics to a clinical prognostic model in patients with low-grade glioma
Authors: M van Riel, F Incekara, S van der Voort, M Wijnenga, S Klein, M van den Bent, M Smits
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND In recent years, radiomics has become of increasing interest in studies of patients with low-grade glioma (LGG). Imaging features extracted from Magnetic Resonance Imaging (MRI) have shown to have the potential to predict genotype and overall survival in patients with LGG. However, until now, the potential of radiomics to add prognostic value to clinical prognostic models has hardly been investigated.The purpose of this study is to investigate the added prognostic value of quantitative magnetic resonance imaging features to a clinical prognostic model for patients with LGG. MATERIAL AND METHODS This retrospective cohort study included adult patients with newly diagnosed LGG who underwent tumor resection or biopsy between October 2002 and March 2017 at the Erasmus MC, University Medical Center Rotterdam (EMC). A set of 77 imaging features were extracted from preoperative T1w and T2w magnetic resonance sequences. These included first order histogram, texture, shape and location features of the volume of interest. The primary outcome of our study was overall survival (OS) and the secondary outcomewas progression-free survival (PFS). RESULTS A total of 259 patients were included. The median follow-up was 5.3 years (interquartile range, 3.4–8.2). The median OS was 9.08 years (95% CI: 6.70–11.5). Four imaging features increased the fit of our clinical prognostic model for OS significantly: T1 local binary pattern peak (hazard ratio (HR) 1.028, p=0.041), T2 histogram energy (HR 1.000, p&lt;0.001), T2 histogram peak (HR 1.000, p=0.002) and standard deviation of radial distance (SDRD) (HR 1.412, p&lt;0.001). The median PFS was 4.14 years (95% CI: 3.49–4.79). Only one imaging feature increased the fit of our clinical prognostic model for PFS significantly: standard deviation of radial distance (HR 1.278, p=0.006). CONCLUSION This study demonstrates that several radiomics features have the potential to help predict OS and PFS in patients with LGG more accurately than models constituted only by clinical features. In our study, four quantitative MRI features were found to be of added prognostic value. However, future studies should validate our results.
Swiss sports and exercise medicine: educate and activate
Authors: Boris Gojanovic
Journal: British Journal of Sports Medicine (2019)

Welcome to the 2019 Swiss Sports Medicine issue of BJSM. Our past 2 years have been busy with the development of interdisciplinary collaborations and the involvement of undergraduates in sports and exercise medicine (SEM). These have led to the successful #sportsuisse2018 Hip and Groin conference with our friends from the Swiss Sports Physiotherapy Association, and the continuation of our yearly Student’s Day, a preconference event to our Annual Meeting. Sports medicine being the dynamic branch that we cherish, we strive to bring new projects to life, in order to disseminate knowledge and improve the well-being of our Swiss population. Two new domains have kept us busy recently: the reform of our national sports medicine curriculum and the development of the ‘exercise’ component in Swiss SEM.

Under the leadership of Drs Andre Leumann and Kerstin Warnke, the Swiss Sports Medicine Society set out to revise our curriculum to bring the best current content to our future graduates. New topics have emerged in the past few years, and doctors’ expanded activities in SEM mean this must …