tbuckley/cabot-search huggingface dataset:
P04.10 Use of MR spectroscopy and diffusion weighted MR imaging for differentiation of glioblastoma relapse and pseudoprogression after complex oncology treatment: final study results
Authors: R. Jancalek, M. Bulik, T. Kazda
Journal: Neuro-Oncology (2017)

The accurate identification of glioblastoma progression remains an unmet clinical need. The aim of this prospective single-institutional study is to determine and validate thresholds for the main metabolite concentrations obtained by MR spectroscopy (MRS) and the values of the apparent diffusion coefficient (ADC) to enable distinguishing tumor recurrence from pseudoprogression. Thirty-nine patients after the standard treatment of a glioblastoma underwent advanced imaging by MRS and ADC at the time of suspected recurrence - median time to progression was 6.7 months. The highest significant sensitivity and specificity to call the glioblastoma recurrence was observed for the total choline (tCho) to total N-acetylaspartate (tNAA) concentration ratio with the threshold ≥1.3 (sensitivity 100.0% and specificity 94.7%). The ADCmean value higher than 1313 x 10−6 mm2/s was associated with the pseudoprogression (sensitivity 98.3%, specificity 100.0%). The combination of MRS focused on the tCho/tNAA concentration ratio and the ADCmean value represents imaging methods applicable to early non-invasive differentiation between a glioblastoma recurrence and a pseudoprogression. However, the institutional definition and validation of thresholds for differential diagnostics is needed for elimination of setup errors before implementation of these multimodal imaging techniques into clinical practice, as well as into clinical trials.The project is supported by grants IGA MZCR NT/14120 and NT/14600.
THE EFFECT OF NORDIC HAMSTRING EXERCISE ON HAMSTRING INJURY IN PROFESSIONAL RUGBY UNION
Authors: Kate Evans, Morgan Williams
Journal: British Journal of Sports Medicine (2017)

Background The incidence of hamstring injuries (HSI) in professional rugby union is high. Nordic hamstring exercise (NHE) has been utilised within HSI prevention programmes. To date, little is known about the effect of NHE on HSI in professional rugby. Objective To examine the effect of a HSI prevention programme on Nordic eccentric strength (NES), injury incidence and severity in professional rugby union. Design Prospective time series design that involved measures of NES obtained throughout the 2015–2016 rugby season whist undertaking a hamstring strengthening intervention. Setting Professional rugby union. Patients (or Participants) 50 professional male rugby union players. Interventions (or Assessment of Risk Factors) One session of 3 sets 3–6reps NHE in addition to normal posterior chain strengthening exercises weekly. Main Outcome Measurements NES was measured at 3 monthly intervals through the season using a commercial device. HSI incidence and severity (days lost) were compared between two seasons. Results From June 2015 to June 2016 NES remained stable (n=31; 5N; 95%CI=−52 to 42N; P=0.821; ES=0.06). Imbalance, however, reduced by 9% (95% CI=3 to 15% (n=31; P=0.005; ES=0.72). For season 2014–2015, number of HSI were 5.2/ 1000 match hours and 0.25/1000 training hours (total of 0.67/1000 hours). During the intervention season, HSI incidence was halved during match play (2.63/1000 match hours) yet, training HSI were 0.37/1000 hours giving a total incidence of 0.56/1000 hours. HSI severity reduced from 124 d in the 2014–2015 season to 99 d in the 2015–2016 season. Conclusions One weekly NHE session successfully reduced match incidence, overall incidence and severity of HSI in professional rugby union. NES remained stable through the intervention and imbalance demonstrated significant reductions. Retention testing at the end of the 4 week off-season period revealed NES had returned to baseline, however imbalance remained significantly reduced.
MOUTHGUARD USE IN YOUTH ICE HOCKEY AND THE RISK OF CONCUSSION AND DENTAL INJURIES
Authors: Dirk Chisholm, Christine Atkins, Luz Palacios-Derflingher, Kathryn Schneider, Carolyn Emery, Brent Hagel
Journal: British Journal of Sports Medicine (2017)

Background Concussion is the most common injury in youth ice hockey. Mouthguards can play a role in reducing the risk dental injuries; however there is limited evidence evaluating their association with concussion in youth ice hockey. Objective To assess the association between mouthguard use and risk of concussion and dental trauma in youth ice hockey. Design Nested case-control. Setting Youth ice hockey leagues (elite and non-elite) in Calgary, Canada, where mouthguard use is not mandatory. Participants Baseline and injury data were collected for 11–17 year old players from 2013–2016. Assessment of Risk Factors Mouthguard use at time of injury as reported on Injury Report Forms. Main Outcome Measurements Case groups were defined as concussed players (therapist suspected or study physician diagnosed) and those with dental injuries; controls were players who sustained a non-concussion/non-dental injury during a game or practice. Only the first injury sustained within or between seasons was included. Frequency of mouthguard usage between cases and controls was compared. Information on baseline self-reported mouthguard use and type was also collected. Results At baseline, the majority of players self reported always wearing a mouthguard during games 2,156/2,606 (82.7%) and practices 1,853/2,539 (73.0%). No dental injuries were reported during the study period. Amongst concussion cases 147/185 players (79.5%) reported mouthguard use at time of injury, compared with 134/147 controls (91.2%) (unadjusted OR=0.38 95% CI 0.18–0.76). Future analyses will include multivariable logistic regression adjusting for relevant covariates and considering effect modification. The effect of mouthguard type at time of injury, and concordance between mouthguard use at baseline and time of injury will also be examined. Conclusions The majority of players self reported always wearing a mouthguard at baseline when there was not mandatory enforcement. Based on preliminary univariate analyses, mouthguard use was associated with reduced odds of concussion.
Contents, Vol. 14, 1966
Authors: R. Hassler, F. Duensing, H. Sommer, G.S. Barolin, R. Alnaes, G. Kienle, A.W. von Eiff, H. Roemer, A. Mellgren, H.J. Prill, E. Schaetzing, W. Dogs, J. Lassner, R. Frey, K. Schürmann, I. Horvai, W.P.J. Vië;tor, J.M. Zwart, D. Langen, D. Langen, E. Svalland
Journal: Psychotherapy and Psychosomatics (1966)
P14.15 Improving survivorship in brain metastases patients: results of a targeted intervention to address educational needs in non neuro-oncology professionals
Authors: E. Molloy, S. M. Robson
Journal: Neuro-Oncology (2017)

Background: Outcomes of patients treated for brain metastases are improving, with a growing number of long-term survivors following surgery and stereotactic radiosurgery (SRS). Many patients continue predominantly under the care of their site specific team (breast, lung etc). It was proposed that survivorship in brain metastases patients might be enhanced by assessing and addressing neuro-oncology-specific educational needs in less specialised health professionals. Aims: To identify education needs of health care professionals regarding treatment of brain metastases. To provide a comprehensive educational package to meet the needs identified. Methods: Educational needs in non-neuro-oncology professionals involved in the care of brain metastases patients were evaluated via a baseline survey addressing their confidence in managing neuro-oncology problems. The questionnaire was electronically disseminated to an unselected, diverse group of health professionals including primary care physicians, nurses and allied health professionals in hospital and community settings. The results were collated to inform the content of the training. Results: 266 responses were received, although, as it was disseminated electronically the response rate cannot be calculated. A whole-day training event was designed around the responses. Topics covered the acute and late toxicity of brain metastases treatments, management of epilepsy, emergencies and the role of rehabilitation in preserving function and enhancing quality of life. Surveys of attendees’ confidence in managing aspects of care were completed at registration, end of day and 5 weeks later. A two-sample Wilcoxon rank-sum (Mann-Whitney) test was applied to compare the data and the results showed statistically significant improvement in confidence across all aspects for both comparisons, suggesting that the attendees benefitted on the day and that the benefit was retained after the event. Conclusion: Significant unmet educational need was demonstrated in the confidence of non-neuro-oncology professionals caring for brain metastases patients. Targeted educational intervention achieved durable, measurable improvement. Further work to addressing survivorship in brain metastases populations is warranted. The project was supported by an innovation grant awarded by Macmillan Cancer Support.
PTEN Down‐Regulation Promotes β‐Oxidation to Fuel Hypertrophic Liver Growth After Hepatectomy in Mice
Authors: Ekaterina Kachaylo, Christoph Tschuor, Nicolas Calo, Nathalie Borgeaud, Udo Ungethüm, Perparim Limani, Anne‐Christine Piguet, Jean‐Francois Dufour, Michelangelo Foti, Rolf Graf, Pierre A. Clavien, Bostjan Humar
Journal: Hepatology (2017)

In regenerating liver, hepatocytes accumulate lipids before the major wave of parenchymal growth. This transient, regeneration‐associated steatosis (TRAS) is required for liver recovery, but its purpose is unclear. The tumor suppressor phosphatase and tensin homolog (PTEN) is a key inhibitor of the protein kinase B/mammalian target of rapamycin axis that regulates growth and metabolic adaptations after hepatectomy. In quiescent liver, PTEN causes pathological steatosis when lost, whereas its role in regenerating liver remains unknown. Here, we show that PTEN down‐regulation promotes liver growth in a TRAS‐dependent way. In wild‐type mice, PTEN reduction occurred after TRAS formation, persisted during its disappearance, and correlated with up‐regulated β‐oxidation at the expense of lipogenesis. Pharmacological modulation revealed an association of PTEN with TRAS turnover and hypertrophic liver growth. In liver‐specific Pten –/– mice shortly after induction of knockout, hypertrophic regeneration was accelerated and led to hepatomegaly. The resulting surplus liver mass was functional, as demonstrated by raised survival in a lethal model of resection‐induced liver failure. Indirect calorimetry revealed lipid oxidation as the primary energy source early after hepatectomy. The shift from glucose to lipid usage was pronounced in Pten–/– mice and correlated with the disappearance of TRAS. Partial inhibition of β‐oxidation led to persisting TRAS in Pten –/– mice and abrogated hypertrophic liver growth. PTEN down‐regulation may promote β‐oxidation through β‐catenin, whereas hypertrophy was dependent on mammalian target of rapamycin complex 1. Conclusion : PTEN down‐regulation after hepatectomy promotes the burning of TRAS‐derived lipids to fuel hypertrophic liver regeneration. Therefore, the anabolic function of PTEN deficiency in resting liver is transformed into catabolic activities upon tissue loss. These findings portray PTEN as a node coordinating liver growth with its energy demands and emphasize the need of lipids for regeneration. (H epatology 2017;66:908–921).
Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey
Authors: Takashi Kokudo, Kiyoshi Hasegawa, Yutaka Matsuyama, Tadatoshi Takayama, Namiki Izumi, Masumi Kadoya, Masatoshi Kudo, Shoji Kubo, Michiie Sakamoto, Osamu Nakashima, Takashi Kumada, Norihiro Kokudo
Journal: Hepatology (2017)

Because of the rarity of hepatic vein tumor thrombus (HVTT) compared with portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma, little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. We analyzed data for 1,021 Child-Pugh A hepatocellular carcinoma patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 who underwent liver resection (LR) and 481 who received other treatments were compared. Propensity scores were calculated, and we successfully matched 223 patients (49.0% of the LR group). The median survival time in the LR group was 2.89 years longer than that in the non-LR group (4.47 versus 1.58 years, P < 0.001) and 1.61 years longer than that in the non-LR group (3.42 versus 1.81 years, P = 0.023) in a propensity score-matched cohort. After curative resection, median survival times were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 versus 4.67 years, P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16 patients). In patients without PVTT, the median survival time was significantly better than that in patients with PVTT (5.67 versus 1.88 years, P < 0.001).LR is associated with a good prognosis in hepatocellular carcinoma patients with HVTT, especially in patients without PVTT. (Hepatology 2017;66:510-517).
Phase 1 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients with CD20+ B-Cell Malignancies Previously Treated with CD20-Directed Antibody Therapy
Authors: Rajat Bannerji, Jennifer R. Brown, Ranjana H Advani, Jon Arnason, Susan M. O'Brien, John N. Allan, Julio C. Chavez, Jeffrey A. Barnes, Robin Joyce, Stephen Ansell, Max S Topp, Lieve Adriaens, Melanie Ufkin, Ana Kostic, Anne Paccaly, Bo Gao, Pamela A. Trail, Israel Lowy, Carrie Brownstein
Journal: Blood (2016)
P15.06 Efficacy and prognostic factors of combined immunochemotherapy R-MPV-A with reduced or deferred radiotherapy for patients with primary CNS lymphoma
Authors: M. Nagane, K. Kobayashi
Journal: Neuro-Oncology (2017)

Backgrounds: R-MPV-A (rituximab plus high-dose (HD) methotrexate (MTX), procarbazine, vincristine followed by high-dose cytarabine) is an active regimen for primary central nervous system lymphoma (PCNSL). A high complete response (CR) rate by the R-MPV induction phase may allow reduction or abbreviation of neurotoxic whole brain radiotherapy (WBRT) with yet favorable outcome. Here we report our single institution experience of R-MPV-A therapy for patients with newly-diagnosed PCNSL to evaluate its efficacy, toxicity, preservation of neurocognitive function and white mater change, along with potential prognostic factors compared with those treated with HD-MTX alone in the previous era. Methods: Thirty-two cases with newly diagnosed PCNSL treated with R-MPV-A since 2012 with more than 6 months from the diagnosis were eligible. There were 19 males and 13 females, mean age was 69.3 yo (range 34-90, 53% were 70 or older), and median KPS was 70 (30-90). R-MPV was applied for 5 to 8 cycles. CR cases received either 24 Gy WBRT (< 70 yo) or no WBRT (>=70), followed by HD-cytarabine for 2 cycles. KPS, MMSE, and Fazekas score were recorded longitudinally. Known clinical factors and molecular factors including MGMT promoter methylation and MYD88 mutation, and expression of mismatch repair (MMR) proteins were also analyzed. Results: Most (88%) cases received 5 or more cycles of R-MPV and WBRT was dose-reduced or omitted in 85% of cases as planned. CR/CRu to R-MPV was achieved in 77%, while there were only 7 (22%) progressions and 4 (13%) deaths with median follow-up for 24.6 months (3.5-58). These outcomes were significantly better than those with previously used HD-MTX monotherapy plus WBRT where CR/CRu rate was 18% with mPFS 9.9 m and mOS 45.2 m. KPS improved in 73% and was maintained in 24, while MMSE and Fazekas score were improved or maintained in 20/23 (87%) and 21/26 (81%), respectively. KPS and MMSE scores dropped only at disease progression. No cases with WBRT omission experienced worsening of Fazekas score except for one with progression. Univariate analysis for PFS reveals single lesion (p=0.010), resection (vs. biopsy, p=0.015), age (<70, p=0.059), MMSE (>=24, p=0.025), methylated MGMT (p=0.056), high expression of MSH6 (p=0.047), and Bcl-2 (p=0.036) as favorable factors. MYD88 L265P mutation status was not associated with PFS. Conclusions: R-MPV-A confers a high CR rate even in elderly patients with improvement and preservation of daily activity, neurocognitive and radiological status. MGMT and MSH6 status might predict outcome after R-MPV-A therapy. Further exploration may be needed for prognostic factors.
Citizens’ assembly recommends unrestricted access to abortion in Ireland
Authors: Gareth Iacobucci
Journal: BMJ (2017)

All women in the Republic of Ireland should be able to access a legal abortion, a public forum has recommended.

The Citizens’ Assembly, which was set up to advise the Irish government on constitutional issues, voted 64% to 36% in favour of introducing unrestricted access to abortion.

The vote can only be legislated for after a public referendum, but raises the prospect of a change to Ireland’s strict abortion laws, which allow a pregnancy to be terminated only if there is a serious risk …
Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity
Authors: Claudia Kitzmüller, Julia Kalser, Sonja Mutschlechner, Michael Hauser, Gerhard J. Zlabinger, Fatima Ferreira, Barbara Bohle
Journal: Journal of Allergy and Clinical Immunology (2017)
OS10.3 Randomized Phase 3 Study Evaluating the Efficacy and Safety of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: CheckMate 143
Authors: D. A. Reardon, A. Omuro, A. A. Brandes, J. Rieger, A. Wick, J. Sepulveda, S. Phuphanich, P. de Souza, M. S. Ahluwalia, M. Lim, G. Vlahovic, J. Sampson
Journal: Neuro-Oncology (2017)

BACKGROUND: Despite available treatment options for patients (pts) with recurrent glioblastoma (GBM), < 5% of pts survive 5 years beyond initial diagnosis, and no single-agent therapy has demonstrated a survival benefit in the second-line setting, including bevacizumab (bev), which is approved for the treatment of recurrent disease. Nivolumab (nivo), a fully human IgG4 monoclonal antibody that inhibits the programmed death 1 receptor, has provided clinical benefit in multiple cancer types. In cohort 2 of the open-label, phase 3 CheckMate 143 study (NCT02017717), the efficacy and safety of nivo was compared with that of bev in pts with GBM experiencing their first recurrence after prior radiotherapy (RT) and temozolomide (TMZ). METHODS: Pts with no prior VEGF therapy were randomized 1:1 to receive nivo 3 mg/kg Q2W or bev 10 mg/kg Q2W until confirmed disease progression; pts were stratified by the presence/absence of measurable disease. The primary endpoint was overall survival (OS); secondary endpoints were 12-mo OS rate and investigator-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Assessment in Neuro-Oncology criteria. RESULTS: At the time of final analyses (Jan 20, 2017), 369 pts were randomized to the nivo (n = 184) or bev (n = 185) treatment arms; of these pts, 182 received nivo and 165 received bev. At baseline, most pts in the nivo (83%) and bev (84%) arms had measurable disease, and 40% (nivo) and 43% (bev) of pts required corticosteroids, with 14% (nivo) and 15% (bev) receiving ≥ 4 mg/day. Deaths were reported in 154 (nivo) and 147 (bev) pts; median OS was 9.8 mo with nivo and 10.0 mo with bev, and the 12-mo OS rate was 42% in both arms. PFS medians were 1.5 mo (nivo) and 3.5 mo (bev). Among evaluable pts treated with nivo (n = 153) or bev (n = 156), ORRs were 8% (nivo) and 23% (bev); duration of response medians were 11.1 mo (nivo) and 5.3 mo (bev). Treatment-related AEs (TRAEs) occurred in 57% (nivo) and 58% (bev) of pts; the most common TRAEs (≥ 10% of pts in either arm; nivo vs bev) were fatigue (21% vs 14%) and hypertension (1% vs 22%). Grade 3–4 TRAEs were reported in 18% (nivo) and 15% (bev) of pts. Serious AEs (all causality) were reported in 46% (nivo) and 35% (bev) of pts; seizure (8% vs 6%) and malignant neoplasm progression (11% vs 7%) were the only serious AEs reported in ≥ 5% of pts in either arm. AEs leading to discontinuation occurred in 10% (nivo) and 15% (bev) of pts. CONCLUSIONS: Nivo did not demonstrate an improved OS compared with bev in pts with recurrent GBM. The ORR was lower with nivo than bev; however, responses with nivo were more durable. The safety profile of nivo was consistent with that observed in other tumor types. Studies of nivo in combination with RT ± TMZ in pts with newly diagnosed GBM are ongoing.
Corrigendum to “Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration” [Metabolism vol. 70, May 2017, pages 31–41]
Authors: Jessica A. Alvarez, Elizabeth Y. Chong, Douglas I. Walker, Joshua D. Chandler, Ellen S. Michalski, Ruth E. Grossmann, Karan Uppal, Shuzhao Li, Jennifer K. Frediani, Rabindra Tirouvanziam, ViLinh T. Tran, Vin Tangpricha, Dean P. Jones, Thomas R. Ziegler
Journal: Metabolism (2017)
Correlation of quantitative total HER2 expression and HER2 homodimers with histopathologic characteristics of breast cancers in the FinHer study
Authors: W. Huang, J. Weidler, Y. Lie, J. Whitcomb, M. Leinonen, P. Bono, J. Isola, P. Kellokumpu-Lehtinen, M. Bates, H. Joensuu
Journal: Journal of Clinical Oncology (2009)

11061 Background: We recently reported that the HERmark assay (Monogram Biosciences) accurately measures continua of total HER2 expression (H2T) and HER2 homodimers (H2D) over a wide (∼3 logs) dynamic range, and that a higher concordance was observed between H2T and HER2 status with more stringent central tests as compared with IHC tests performed locally (Joensuu et al, 2008 SABCS,abstract 2071). H2D/H2T ratio was reported as a marker of activated HER2 and a prognosticator of disease progression in HER2+ patients not treated with trastuzumab in the adjuvant setting (Bates et al, 2008 SABCS,abstract 1074). In this follow-up analysis, H2T, H2D, and H2D/H2T ratio were correlated with histopathologic characteristics of breast cancers in the FinHer study. Methods: The HERmark assay was used to measure H2T and H2D in 899 formalin-fixed, paraffin-embedded FinHer specimens. The results were correlated with histopathologic characteristics of breast cancers in the FinHer study (Joensuu et al, N Engl J Med2006;354), including estrogen receptor/progesterone receptor (ER/PR), tumor grade, tumor size, lymph node metastasis, and stage. Results: Higher H2T and H2D levels correlated with ER/PR negativity and high tumor grade (P&lt;0.0001). 42% (102/244) of ER- and 37% (137/374) of PR- cases were HERmark Positive; while 17% (110/655) of ER+ and 14% (75/524) of PR+ cases were HERmark Positive. 10% (13/136) of grade 1, 18% (65/353) of grade 2, and 35% (131/375) of grade 3 tumors were HERmark Positive. No significant association was found between H2T or H2D and tumor size, lymph node metastasis or stage. ER/PR negative and poorly differentiated cancers had higher H2D/H2T ratios (P=0.013), and H2D/H2T ratios &gt;0.6 were associated with smaller primary tumor diameters at the time of cancer detection (P=0.009). Conclusions: The quantitative H2T measurement confirms the known correlations between HER2 expression and histopathologic characteristics of breast cancer. The novel H2D measurement and H2D/H2T ratio may provide further insights into HER2 activation and better diagnostic tests for targeted HER2 therapy. [Table: see text]