tbuckley/cabot-search huggingface dataset:
P16.27 Spinal metastasis of thymic carcinoma: a rare manifestation
Authors: C. Sousa, J. Monteiro, R. Manilha, D. Gonçalves, C. Gradil, C. Viegas, A. Amorim, A. Oliveira, M. Cunha e Sá
Journal: Neuro-Oncology (2017)

Introduction: Despite the highly aggressive behaviour of thymic carcinomas, extra-thoracic metastasis and specifically spinal metastasis are very rare and sparsely reported. For that reason, the survival and the natural course of the disease are not yet clearly elucidated. Materials and Methods: We report on one patient with spinal metastasis from thymic carcinoma who had surgical removal performed in our institute, following progressive weakness of both legs associated with flank and lower back pain. The patient had a paravertebral and anterior intracanalar epidural mass compressing the spinal cord at the T12 level. The clinical, radiological, surgical and pathological features of this abnormality are discussed and the case reviewed. Results: A laminectomy at T12 and partially at T11 and L1 were performed via a posterior approach and the histopathological diagnosis was a metastasis from a thymic origin. The patient presented a mild improvement of the presenting neurological deficits and the back pain was relieved completely, with no observed complications. The period from the primary diagnosis to spinal metastasis was 3 years. Posteriorly, the patient presented 2 episodes of seizures, leading to the diagnosis of 2 ring-enhancing lesions in the right hemisphere (on CT), with no further histological or imagiological investigation. She was proposed for adjuvant spinal and holocranial radiotherapy, but died approximately one moth after surgery due to pulmonary complications associated with disease progression. Conclusions: Spinal metastasis of thymic carcinoma are very rare, and we could find only a few cases reported. Due to its rarity, there are no treatment guidelines. Even so, we suggest that appropriate surgical removal of the metastatic lesion is necessary to treat refractory severe pain and a potential reversible neurologic deficit, in order to preserve the patient’s quality of life.
A Phase I/II Clinical Trial of the First-in-Class GPCR Antagonist ONC201 in Relapsed/Refractory Acute Leukemias
Authors: Gautam Borthakur, Jo Ishizawa, Courtney D DiNardo, Tapan M. Kadia, Katherine Weise, Joshua E Allen, Wolfgang Oster, Jorge E. Cortes, Hagop M. Kantarjian, Michael Andreeff
Journal: Blood (2016)
Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis
Authors: Silje Halvorsen Sveaas, Geir Smedslund, Kåre Birger Hagen, Hanne Dagfinrud
Journal: British Journal of Sports Medicine (2017)

Objective To investigate the effects of cardiorespiratory and strength exercises on disease activity for patients with inflammatory rheumatic diseases (IRDs). Design A systematic review with meta-analysis registered at PROSPERO ( CRD42015020004 ). Participants Patients with IRDs. Data sources The databases MEDLINE, AMED, Embase and CINAHL were searched from inception up to April 2016. Eligibility criteria for selecting studies Trials were included if they were randomised controlled trials of adults with IRDs, comparing the effect of cardiorespiratory and strength exercises with usual care on disease activity and followed the American College of Sports Medicine's exercise recommendations. The primary outcome was disease activity in terms of inflammation, joint damage and symptoms. Data synthesis Data were pooled in a random-effect model for all outcomes, and standardised mean differences (SMDs) were calculated. The quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. Results Twenty-six trials with a total of 1286 participants were included. There was high to moderate quality evidence, for a small beneficial effect on disease activity scores (0.19 (95% CI 0.05 to 0.33), p&lt;0.01) and joint damage (SMD 0.27 (95% CI 0.07 to 0.46), p&lt;0.01). Furthermore, moderate quality evidence for a small beneficial effect on erythrocyte sedimentation rate (SMD 0.20 (95% CI 0.0 to 0.39), p=0.04) and for no effect on C reactive protein (SMD −0.14 (95% CI −0.37 to 0.08), p=0.21). Beneficial effects were also seen for symptoms. Conclusions The results of this review suggest beneficial effects of exercises on inflammation, joint damage and symptoms in patients with IRDs.
Association of Donor Age and Sex With Survival of Patients Receiving Transfusions
Authors: Gustaf Edgren, Henrik Ullum, Klaus Rostgaard, Christian Erikstrup, Ulrik Sartipy, Martin J. Holzmann, Olof Nyrén, Henrik Hjalgrim
Journal: JAMA Internal Medicine (2017)

Following animal model data indicating the possible rejuvenating effects of blood from young donors, there have been at least 2 observational studies conducted with humans that have investigated whether donor age affects patient outcomes. Results, however, have been conflicting.To study the association of donor age and sex with survival of patients receiving transfusions.A retrospective cohort study based on the Scandinavian Donations and Transfusions database, with nationwide data, was conducted for all patients from Sweden and Denmark who received at least 1 red blood cell transfusion of autologous blood or blood from unknown donors between January 1, 2003, and December 31, 2012. Patients were followed up from the first transfusion until death, emigration, or end of follow-up. Data analysis was performed from September 15 to November 15, 2016.The number of transfusions from blood donors of different age and sex. Exposure was treated time dependently throughout follow-up.Hazard ratios (HRs) for death and adjusted cumulative mortality differences, both estimated using Cox proportional hazards regression.Results of a crude analysis including 968 264 transfusion recipients (550 257 women and 418 007 men; median age at first transfusion, 73.0 years [interquartile range, 59.8-82.4 years]) showed a U-shaped association between age of the blood donor and recipient mortality, with a nadir in recipients for the most common donor age group (40-49 years) and significant and increasing HRs among recipients of blood from donors of successively more extreme age groups (<20 years: HR, 1.12; 95% CI, 1.10-1.14; ≥70 years: HR, 1.25; 95% CI, 1.08-1.44). Higher mortality was also noted among recipients of blood from female donors (HR, 1.07; 95% CI, 1.07-1.07). Adjustments for number of transfusions with a linear term attenuated the associations, but the increased mortality for recipients of blood from young, old, and female donors was not eliminated. Closer examination of the association between number of transfusions and mortality revealed a nonlinear pattern. After adjustments to accommodate nonlinearity, donor age and sex were no longer associated with patient mortality.Donor age and sex were not associated with patient survival and need not be considered in blood allocation. Any comparison between common and less common categories of transfusions will inevitably be confounded by the number of transfusions, which drives the probability of receiving the less common blood components. Previous positive findings regarding donor age and sex are most likely explained by residual confounding.
Lessons from the lower airway microbiome in early CF
Authors: Jordana E Hoppe, Edith T Zemanick
Journal: Thorax (2017)

Lung disease in cystic fibrosis (CF) is characterised by chronic airway infection and inflammation.1 Advances in sequencing technology have expanded our understanding of airway infection in CF, with complex polymicrobial bacterial communities frequently detected along with typical CF bacterial pathogens such as Pseudomonas aeruginosa .2 Investigations of CF airway microbiota rely on interrogation of airway samples, most commonly expectorated sputum. Young children with CF rarely expectorate sputum spontaneously, leaving clinicians with the option of oropharyngeal swabs which may not reflect lower airway bacteriology or bronchoalveolar lavage fluid (BALF) collection which requires an invasive procedure with anaesthesia.3

Microbial diversity, a measure that takes into account the number of different bacterial taxa and the relative amount of each taxa detected within a community, has been associated with disease status in CF with lower diversity associated with lower lung function, the presence of pathogenic bacteria and increased airway inflammation.4–6 Microbial analyses of CF samples from younger, healthier patients often show highly diverse bacterial communities,7 whereas lung explants from patients with end-stage lung disease reveal extremely low diversity with typically only one or two pathogenic bacteria detectable.8 The transition from a diverse community to one dominated by CF pathogens likely begins early, but difficulty with airway sampling hinders our ability to study changes in young children.

Lung disease begins early in CF with airway infection, inflammation and bronchiectasis, evident as early as 3 months.9 Airway inflammation is tightly linked to development of bronchiectasis, as the presence of BALF neutrophil elastase (NE) in early infancy is strongly associated with bronchiectasis in young children. Airway inflammation is also increased in the presence of known CF pathogens such as P. aeruginosa and Staphylococcus aureus , with less inflammation seen with bacteria detected by molecular approaches but not on conventional routine culture. …
Chronic obstructive pulmonary disease: inhale deeply and start to exercise
Authors: Henrik Watz
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) is defined by partially reversible airflow limitation as a result of either small airway obstruction or loss of elastic recoil due to emphysematous lung destruction, or both [1]. Airflow limitation resulting from small airway obstruction is treated with bronchodilators. Resulting improvements in airflow limitation are in turn quantitatively assessed by measuring the forced expiratory volume in 1 s (FEV1), which is the most widely used spirometric measure in COPD. In fact, most of our knowledge about the magnitude of improvements from bronchodilator therapy comes from this standard measurement of lung function. So we know that the simultaneous inhalation of long-acting muscarinic antagonists and long-acting beta-2 agonists from one inhaler once or twice daily results in improvements in FEV1 that are superior to the inhalation of the individual components [2–5] and clearly exceed the threshold for clinical importance of ∼100 mL [6]. Dual bronchodilation results in better lung deflation but similar exercise capacity compared to LAMA monotherapy <http://ow.ly/7zL1309M6LK>
THE IMPLEMENTATION AND ADOPTION OF THE INJURY PREVENTION EXERCISE PROGRAMME GAA 15 IN GAELIC FOOTBALL CLUB TEAMS IN THE COUNTIES OF MAYO AND LONDON
Authors: John Reilly, Courtney Kipps
Journal: British Journal of Sports Medicine (2017)

Background Injury prevention exercise programmes (IPEPs) have been shown to prevent and reduce injuries in team sports (Silvers-Granelli et al . 2015, Owoeye et al . 2014). Implementation and adoption of IPEPs in team sport is a process is multifaceted and complex (Donaldson &amp; Finch 2013). The Gaelic Athletic Association (GAA) has produced an IPEP (GAA 15) specifically tailored to Gaelic football. Objective To investigate the injury prevention knowledge, beliefs and perceptions of GAA coaches and estimate the implementation rates of the ‘GAA 15' Design Cross-sectional survey. Setting Gaelic football clubs in the Counties of Mayo and London. Patients (or Participants) 26 GAA coaches who responded to email invitations to participate in this study. Interventions (or Assessment of Risk Factors) Online web based survey related to Gaelic football injuries and injury prevention. Main Outcome Measurements Understanding and perceptions of injury prevention in general; implementation of the ‘GAA 15’; and the motivation and support from the GAA and their County Boards. Results All but one coach (96%) believed that an IPEP would reduce injuries to players during training and matches. Although all coaches utilise selected components of an IPEP such as strength, balance, and core exercises during the warm-up or training, only 2 coaches reported using the ‘GAA 15’. Coaches feel that they do not get enough support and exposure from the GAA and their County boards with regards to injury prevention strategies. The coaches supported the use of online resources, phone applications and group training programmes. Conclusions Despite wide acceptance of the benefits of an IPEP, few coaches use one in Gaelic Football. The results of this study provide valuable information on the knowledge, perceptions and beliefs of Gaelic football club coaches regarding injury prevention. This information should be used to optimise access to education and delivery of the ‘GAA 15’.
Lost in translation: returning germline genetic results in genome-scale cancer research
Authors: Amber L. Johns, Skye H. McKay, Jeremy L. Humphris, Mark Pinese, Lorraine A. Chantrill, R. Scott Mead, Katherine Tucker, Lesley Andrews, Annabel Goodwin, Conrad Leonard, Hilda A. High, Katia Nones, Ann-Marie Patch, Neil D. Merrett, Nick Pavlakis, Karin S. Kassahn, Jaswinder S. Samra, David K. Miller, David K. Chang, Marina Pajic, John V. Pearson, Sean M. Grimmond, Nicola Waddell, Nikolajs Zeps, Anthony J. Gill, Andrew V. Biankin
Journal: Genome Medicine (2017)

The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predisposition to PC or medium–high penetrance genes with well-defined cancer associated syndromes or phenotypes. Variants from candidate genes were annotated and classified according to international guidelines. Variants were considered actionable if clinical utility was established, with regard to prevention, diagnosis, prognostication and/or therapy. A total of 48,904 germline variants were identified, with 2356 unique variants undergoing annotation and in silico classification. Twenty cases were deemed actionable and were returned via previously described RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of our cohort experienced clinical benefit from RoR. Returning research results within the context of large-scale genomics research is a labour-intensive, highly variable, complex operation. Results that warrant action are not infrequent, but the prevalence of those who experience a clinical difference as a result of returning individual results is currently low.
P03.13 Molecular and clinical bio-markers in a series of 48 consecutive skull base chordoma patients
Authors: E. La Corte, M. Patanè, G. M. Campisi, R. C. Paroni, G. Serrao, I. M. Milanesi, S. Visintini, P. Ferroli, R. Ghidoni, B. Pollo
Journal: Neuro-Oncology (2017)

Introduction: Chordoma is a rare tumor arising from the notochord. Its lethality is largely due to its tendency to recur. Precision medicine with molecular target therapies is emerging as a promising approach. The main goal of the present project is to identify molecular and clinical biomarkers as diagnostic, therapeutic and prognostic factors useful for the management of chordoma patients. Materials and Methods: A retrospective clinical and pathological charts review of all chordoma patients treated at our Institution in the last twelve years has been performed. Clinical data were gathered together with the investigation of histopathological tumor features. Kaplan-Meier analysis was used to determine overall survival (OS). In addition, a preliminary immunohistochemical (IHC) analysis was carried out for the following markers: Brachyury, p53, beta-catenin, filamin-A, GAB‐1, EGFR, PDGFR-beta, c-MET, C-kit, PTEN, YKL-40 and TERT. Sphyngolipidomic analysis will be performed to study the ceramide species in prospectively collected frozen specimens of chordomas and nuclei pulposi, as control group. Results: The study included the last consecutive 48 patients. The average follow-up was 42 months (range 3–139). Sixty surgical operations were performed in the initial or recurrent setting. Thirty patients received post-operative radiation therapy and three patients received post-operative chemotherapy. The mean OS and PFS after surgery was 42 and 49 months, respectively. The Kaplan-Meier analysis predicted OS rates of 70%, 60%, 49% and 49% at 3, 5, 7, 10 years, respectively. The preliminary IHC analysis has been conducted on 18 specimens (eleven primary, seven recurrent). All the classical chordoma expressed Brachyury. The analysis showed a positive trend of activation of the tyrosine-kinase receptors (PDGFR-beta, c-MET, c-Kit) and the Sonic-Hedgehog pathway (GAB-1, filamin-A and beta-catenin patterns). There was a phenotypic change in the expression of PDGFR-beta and GAB-1 between the primary tumor and its recurrence after the gold-standard treatment. Interestingly, TERT expression was significantly expressed in 95% of specimens. Conclusion: Kaplan-Meier analysis confirmed that surgical resection entity represented a statistically significant factor related to OS. In the present small cohort of specimens there was a positive expression of PDGFR-beta, showing that this pathway could potentially be targeted by TRKs inhibitors. TERT expression may play a role in enabling primary tumor replicative immortality and may explain the etiology from embryonic notochordal remnants. Our preliminary IHC data showed that the Sonic-Hedgehog could be a potential pathway involved in chordoma pathogenesis that should be further studied.
P19.01 Kampo therapy(Japanese traditional herbal medicine)for peripheral neuropathy complicated with anti-cancer chemotherapy
Authors: A. Hayashi
Journal: Neuro-Oncology (2017)

Background: Peripheral neuropathy due to anticancer chemotherapy is a serious complication. Currently, goshajinkigan is recognized as effective prescription, but its limitation has also become apparent. The author reports the results of goshajinkigan therapy combined with some other herbal medicines. Objectives: From April, 2014 to June, 2016, the following two groups of patients were treated with Kampo therapy. Group 1: 204 patients (male/ female: 47/157), 24-82 years old (mean age 61.0) who had developed peripheral neuropathy complicated by anticancer chemotherapy. Group 2: 45 patients (male / female: 6 / 39), 35-77 years old (mean age 58.0) who received kampo treatment for preventing anticancer chemotherapy induced peripheral neuropathy. Methods: The effectiveness of the treatment was evaluated with numerical rating scale when the neurological improvement was stabilized. The degree of improvement of group 1 was evaluated into four categories from 0 to 100% by 25 %. They are described as excellent, good, fair, and no change, respectively. Group 2 was assessed based on the residual nerve disorder at the completion of chemotherapy. Results: Group 1: excellent 62 cases (30.4%),good 41 cases (20.1%),fair 23 cases (11.3%),no change 44 cases (21.6%),and drop out 34cases (16.7%). Group 2: No residual nerve disorder 25 cases (55.6%),Residual nerve disorder 16 cases (35.6%), and Discontinued 4 cases (8.9%). Discussion: Peripheral neuropathy complicated with anticancer chemotherapy is a major factor for interrupting the treatment. Then, proper therapies are expected to prevent or relieve the complication. According to the traditional oriental medicine, chemotherapy-induced peripheral neuropathy may show blood stagnation, qi (vital energy) stagnation and fluid retention in the micro-environment of around peripheral nerves. The major aim to treat peripheral neuropathy is just to resolve such pathophysiological condition mentioned above and to promote a self-sustained recovery of the peripheral nerves. In recent years, Goshajinkigan has been drawing attention to relieve the complication. Goshajinkigan is a formula based on hachimijiogan in which only a double dosage of the processing Aconite Tuber and 2 crude drugs,Achyranthis Radix and Plantaginis Semen are added. So, the author intended to enforce the action of these three crude drugs. Then, Goshajinkigan combined with Kampo formulation for overcoming blood stagnation, such as keishibukuryogan, sokeikakketsuto, tsudosan; Kampo formulation for tonifying qi such as hochuekkito, kamikihito, the processing Aconite Tuber which also promoting mild diuresis. CONCLUSIONS: In this study, such arrangement of Kampo formula yielded good outcomes. Further studies are required to obtain much better arrangement.